Introduction

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01/01/2001

Introduction to Neuroscience
Early Days
Gross Anatomy of the Brain
Origins of Neuroscience
Neurons and Glia
Classifying Neurons
Case Study (Mental Retardation, Alzheimers)

The study of the Central Nervous System (CNS) and the Peripheral Nervous
system (PNS).

1. Early Days

 People believed that head aches or other forms of pain in the head
was due to bad spirits that were trapped inside the brain. To remove
them, a surgical skull procedure called Trepanation was conducted.
This appeared prominent in human remains from the past

Views of the Brain

Ancient Greece:
o The brain was the seat of intelligence
Roman Empire: Observed and named parts of the brain
o Cerebrum
o Cerebellum
o Ventricles (Cerebral Spinal Fluid CFS)
The Renaissance
o Saw the brain as a machine.
[2. Anatomy of the Brain]

 White Matter : Consists mostly of Glia and myelinated axons that

transmit signals (action potentials) from one region of the brain to
another and essentially affects how the brain learns and functions.
( The wires connecting the computers)
Grey Matter: Is composed of neurons and are associated with
processing information.
(The Computers)

 Cerebrum (Cerebral Cortex)

Frontal Lobe:
Commonly known as the conscious brain where judgments based off
evidence are processed, emotions, speech. (Good and bad, right and wrong)
Parietal Lobe:
A lot of sensory information is integrated from around the body (eg. The
skin)
Occipital Lobe:
The visual processing center of the brain.
Temporal Lobe:
Visual memories, audio processing, deriving meaning, emotions..
Cerebellum
Where a lot of our motor control is processed or cognitive function of
the brain where you the brain processes the sensory information into
decision making, comprehending and producing something.

What are Gyri and Sulci?

s
Gryi are the folds in the brain or the risen parts of the brain whilst the
Sulci are the grooves or depressions on the brain
(The image to the right is fissures of the skin which are a form of
deep sulci)
[3. Origins of Neuroscience]

Nerves as wires
Different parts of the brain for different functions
Evolution of the Nervous System
The Basic Functional Unit: The Neuron

1. Nerves as wires: Bell and Magendie

The phenomena of electricity and that our nerves conducted electricity and that
they travel in one direction (eg: sensory and motor nerves).

Charles Bell and Francois Magendie were two famous physiological

scientists known for their findings of nerves having direction. Their findings
found that nerves were either made of sensory fibers or made of motor fibers
This was concluded by severing the dorsal roots and ventral roots of a nerve
connected at the spine interchangeably. Severing the dorsal root of a nerve
caused loss of sensation and severing the ventral root caused paralysis.

 2. Different parts of the brain serve different functions

- Charles Bell also found through
his research that the origin of these
motor fibers originated in the
Cerebellum part of the brain and that
sensory fibers were found in the
Cerebrum part.
- Pierre Flourens conducted further
research and developed the method of
ablation where certain parts of the brain
were stimulated or removed to see what it
intern affected.

- Broca was well known for his findings

in the location of speech on the brain.
Broca dissected the brain of a man who
could not speak but interpret and found a lesion
(damaged) part on the brain. Today this section
located in the frontal lobe is known as the
Brocas area.

3. Evolution of the Nervous System

Based of Darwins Theory of Evolution and that we evolved from a
common ancestor.
Advantageous traits have been passed on, such as intelligence with in
humans
Similar behavior is found in mammals such as fear. When fear is
stimulated (eg: a lighting strike) the same physiological changes occur
within the mammal such as dilated pupils, increased heart rate,
increased awareness and so on.
The differences between species arose from natural selection.
Best suited to its environment and to survive

4. The Basic Functional Unit: The Neuron

The functioning millions of neurons that integrate together to form the
nervous system.

Dendrites

Soma

Axon

[4. Neurons and Glia]

Glial Cells (Network Wires)

Support Neurons
Nourish Neurons with essential nutrients (Astrocytes)
Protect Neurons from infections/virus. (Microglial)
Insulates Neuronal Cells (Oligodendrocytes)

Neuron Cells ( Computers)

Process information
Send and receive commands

 Sensory and Motor skills

Ependymal Cells

Astrocyte Cell
Neuronal Cell

Oligodendrocyte
Cell

Microglial Cell

Glial Cells
Ependymal Cells: Surround and make the membrane of the brain.
They are commonly known to be involved in making the spinal fuid
inside the ventricles of the brain.
Oligodendrocytes (CNS) : Insulate the neurons axon with myelin to
allow faster transmission signals.
Astrocytes : Surround blood vessels and neurons to supply rich
nutrients to the neuron and surrounding cells.
Microglia: Are the white cells of the brain which protect the neurons
from infection/virus.
Schwann Cells (PNS): Not to be confused with Oligodendrocytes, as they
perform a similar role to insulating neurons with myelin but ONLY in the
peripheral nervous system.

Neuronal Cells
1. Nucleus (DNA)
RNA Transcription
DNA Replication
Gene Expression
2. Soma (Body of the Cell)
Rough ER (Ribosomes)
o mRNA translation

o Protein Synthesis
Golgi Apparatus
o Final assembly of protein and packaging
Smooth ER
o Several Metabolic Processes (production of steroids, lipids..)
Mitochondria (Cellular Respiration)
o ATP manufacturing site
o Glucose Pyruvate ADP ATP
3. Neuronal Membrane
Phospholipid Bi-layer, usually varying in protein richness.
4. Cytoskeleton (Non-Static)
The Bones of the neuron cell, providing a sturdy structure to
maintain shape and function within the cell.

6. The Axon

Axon Hillock (Start)

Axon proper (middle)
Axon Terminal (End)

What

is the difference between the Soma of the cell

and the axon?

As we trail away from the soma we find a

unique composition of proteins along the axon. In
between the Nodes of Ranvier are high densities of Na+
voltage gated channels to allow the action potential signal
to
transmit quickly by jumping the myelin covered
sections to the next node. At the terminal end of
the axon also known as the synapse, there are a large concentration of
mitochondria, an abundance of membrane proteins and presence of synaptic
vesicles.

7. Synapse
Where the Synaptic Gap is located
Action potential (electrical) signal is converted in chemical signal
Release site of Neurotransmitters
Link between Axons and Dendrites
8. Dendrites
Antennas of the Neurons
Incoming signals from other surrounding cells.
[5. Classifying Neurons]

 Uni

Classification by Morphology

-polar

Bipolar
Multi-polar

 Pyramidal shaped neurons

Stellate (Star) shaped neurons

Classification on CNS
Primary Sensory Neurons
Primary Motor Neurons
Interneurons (between neurons)

Further Classification
Based on Axon Length
o Golgi Type 1
o Golgi Type 2
Based on Neurotransmitter Type
o Cholinergic = Acetylcholine
Extra Terminology
-cyte : Denoting a mature cell lymphocyte, astrocyte
-blast : Denoting a embryonic cell osteoblast
[5.Case Study]
Alzheimers Disease
Alzheimers Disease is the slow degeneration of the human brain.
Alzheimer discovered after dissecting a womans brain who showed signs of
memory loss, loss of cognition, deliriousness and confusion that 1/3 of the
neuron cells within her brain had died. Leaving practically nothing of the cell
but the remains of the cytoskeleton.

It is now known today that Alzheimers is caused by the breakdown of

the cytoskeleton inside the cell. This is due to the protein Tau which is
responsible for keeping the microtubules and microfilaments running straight
and parallel together within the cell. But over time in some cases Tau
disconnects from the microtubules and causes the cell to loose its structural
integrity and eventually leave nothing but a accumulation of Tau and parts of
the cytoskeleton that are all tangled.
So why does Tau disconnect from the cytoskeleton?
It is now known through further research that another protein accumulates
within the cell named Amyloid. This protein accumulates and causes the change
in Tau to intern effect the cytoskeleton and eventually cause cell death.
Further research is conducted to intervene the accumulation of Amyloid
within the brain.

Key Proteins Tau disconnects from Cytoskeleton due to the

accumulation of Amyloid
Tau/Amyloid

 Mental Retardation
Mental retardation is considered when the IQ of a person is below the
standardized intelligence of <70 are considered mentally retardation. The Bell
shape curved that distributes the population has a mean of 100.
So what is Mental Retardation exactly?
There are many causes to the mental retardation that branch off into
different conditions. The basis of mental retardation is the when the brain is
affected during development and is unable to develop to its full potential.
Neurons in mentally retarded patients have been seen to contain less dendrites
surrounding the neuron and also the structure of the dendrites. It has been
shown in research that the dendrites of mentally retarded patients contain
abnormal structures and tend to usually long and skinny. This structure has
shown to be very similar to the structure of neurons of a fetus.
What are the causes?

There are a wide range of causes in mental retardation but most of them can
be linked to the early stages of development. One condition is known as
Down Syndrome, where one extra chromosome is found on chromosome 21
and directly affects the development of the brain. Another cause is due to the
malnutrition of the fetus during development. This can be causes due to
common correlations such as drug use, alcoholism in mothers. Another
severe form of mental retardation is formed from a genetic disorder known
as PKU (Phenylketonuria) where the amino acid known as phenylalanine is
over produced in the liver. High concentration of phenylalanine stunts the
growth of the brain. Thankfully, if detected early during development some
of these conditions can be reversed and allow full development of a healthy
brain .
Down Syndrome (Extra chromosome on C 21)
Malnutrition during pregnancy
PKU (Over production of Phenylanaline)

Lecture 2 Action Potentials

Objectives
Understand resting cell membrane potential and how it is
maintained
Understand the role played by voltage gates ion channels, leaky ion
channels and the Na/K ATPase pump.
How is a signal initiated within the Nervous System?

 How is a signal propagated along a nerve fiber?

1. Resting Cell Membrane Potential
2. Properties of Ion Channels
3. The Action Potential and its Initiation
4. Propagation of Action Potential

1. Resting Cell Membrane Potential

Some definitions to consider when we are looking at membrane potential is
neurons..
Membrane Potential (V) is the difference in the number of negatively charged
ions and positively charged ions across the cell membrane. In ALL cells of the
body the inside of a cell is more negatively charged in relation to the outside of
the cell. Membrane potential is measured in volts, intern denoted V.
Current (I) is the measure of the movement of these ions across the cell
membrane. A strong current will move more ions across the membrane in
comparison to a weak current which would move less. The current of ions is
measured in amps, which is denoted I.
Resistance (R) is the amount of unwillingness the cell membrane allows
the ions to cross. A large resistance will slow down the movement ions across a
membrane whilst little resistance will allow them to easily move through.
Resistance is measured in Ohms and is denoted R.
Together they all relate and form the infamous Ohms law equation!

Membrane Potential (V) = Current (I) x Resistance (R)

If the membrane potential is = 0 then there is no movement of ions
across the cell membrane, even if the resistance is very low.
What happens when the Resting Membrane Potential is not equal to
0?

 Cells within the body at rest are never equal to zero!

All cells within the body are negatively charged relative to the outside. In
particular neuronal cells have a resting membrane potential of -65mV.
RESTING CELL MEMBRANE POTENTIAL = -65mV
What is a Resting Cell Membrane Potential?
Resting cell membrane potential is when a cell is within a state of rest.
In other words, it is not being stimulated to form a action potential or a
graded potential.
Membrane potential is described by the potential inside the cell
relative to the outside of the cell.
What creates a Membrane potential in the first place?
The creation of membrane potential is the build up on ions around the
cell membrane. There are some key players involved in determining
what initially sets up a potential difference across the membrane.

Na+

and

K+

Na+ and K+ are the main players that form a concentration gradient
across the cell membrane. Due to the simple law of Diffusion we
know that an area of high concentration wants to diffuse to an area of
low concentration.
In cells, there is a high concentration of potassium K+ and a low
concentration of sodium Na+. Visa versa, there is a high concentration
of Na+ outside the cell and also a low concentration of K+. Intern this
forms a concentration gradient.
Sodium really, really wants to go inside the cell!
Potassium really, really wants to leave the cell!
The role of the semi-permeable membrane stops this. Although there
are leaky ion channels that tend to allow a small flow of ions these
ions in and out of the cell. The cell membrane is more permeable to
K+ rather than Na+.
What forms the actually difference in charges across the cell
membrane?

Intracellular side of the cell has many more proteins that are negatively
charge. Leaving the intracellular cell overall negative (Vm: -65mV)
These proteins tend to form around the cell membrane causing like
charges to attract. Na+ and K+ tend to huddle around the perimeter of
the cell membrane due to the membrane potential.
Further factors contributing to the huddling of charges across the
membrane are led back to leaky ion channels. K+ tend to leak out of
the cell much more than Na+. Intern leaving the cell gradually more
negative and the outside more positive. Creating more of a potential
difference across the cell membrane.
OVERALL when these factors are all placed together we reach a equilibrium
state. This causes the resting cell membrane potential!!! And is attributed to
by a Electro-Chemical Gradient as both a combination of concentration
gradient and electrical gradient (like charges attract) are involved.

RESTING CELL MEMBRANE POTENTIAL = -65mV

1. Resting cell membrane is formed from the build up of positive ions
outside the cell membrane and negative ions inside the cell membrane.

2.

The potential difference is only found around the membrane of the

cell. The further you
migrate away from the cell
membrane there is no
difference as both
are relatively
neutral.
The CELL

MEMBRANE
is now polarized and
has the POTENTIAL to
create a sudden movement of ions across this membrane, but it is
currently in a state of REST or equilibrium.
RESTING CELL MEMBRANE POTENTIAL
Modeling Resting Cell Membrane Potential

Em =
particular
that is permeable.
Ek

the equilibrium potential of a

ion, considering it is the only ion

or ENa as an example.

Note : The Nernst Equation

only takes into
consideration the membrane is permeable to one ion, when in fact there are
more contributing ions and permeability of each of the ions that will give
you the resting cell membrane potential of the cell as a whole. The Nernst
equation denotes the Equilibrium potential of just one particular ion.

GHK (Goldman Equation):

Takes into the
consideration the
permeability and different
ions to model the resting
cell membrane potential.
this is equal to Vm (The
Cell Membrane Potential)
2. Properties of Ion Channels
Types of ion channels
Diffusion, Channel protein, Carrier protein (Passive), Na/K Pump
(Active)

Leaky ion channels

leaky ion channels are found within the cell membrane. Theyre a
contributing factor for the maintenance of resting cell membrane potential.
K+ tends to leak out of the cell faster than Na+ being brought into the cell,
overall leaving the cell more negative.
Na+/K+ Pump

Another pump that ensures the maintenance of K+ being more concentrated

inside the cell than sodium is the Sodium Potassium pump. The Na/K
pump is driven by ATP to push 3 atoms of Na+ out for every 2 K+ brought
into the cell. ATP is needed to push Na+ out of the cell against its
concentration gradient.
Leaky channels + Na+/K+ Pump = Resting Cell Membrane Potential

3 Na+ out 2 K+ in

(a) Na+/K+ Pump)

Chemical Gated Channels

(b) Leaky channels

A membrane protein channel that is chemically gated. The protein

changes molecular conformation when a substrate, ligand, or chemical attaches
to the channel and causes it to open. eg, Neurotransmitter/liga

Voltage Gated Channels

A membrane protein that responds to changes in membrane potentials.
The protein will change molecular when it is stimulated by a change in
membrane potential eg. Depolarization stimulates Na+ voltage gated
channels to open and allow Na+ to rush into the cell. (interneurons)

Mechanical Gated Channels

A membrane protein that changes its molecular conformation from
mechanical/physical stimulus. The membrane stretches and causes these
channels to open. Mechanoreceptors found in the sensory neurons contain a
high concentration of mechanoreceptors on their dendrites

3. The Action Potential and its Initiation

Graded Potential
Action Potential
Graded Potential
A graded potential is small changes with the membrane potential but
not enough to propagate an action potential within the cell.
Graded potentials dont reach the threshold to cause a action potential
and are short lived, signals that depreciate over an area.
It may take many graded potentials to reach threshold before the
whole cell can depolarize and form an action potential.

An example of a graded potential is the hyperpolarization of a cell and

a graded depolarization. An you can see they both (even the positive)
dont reach the threshold.
Action Potential
The all or nothing principle. A sudden change in membrane
potential causes the cell to depolarize and create an action potential
that propagates down the axon.

 The signal does not grow weaker and propagates effectively from
neuron to neuron.
The Action Potential Steps
1. A form of stimulus comes along and causes a channel to open. Examples
include neurotransmitters that connect to chemically gated proteins, a
stretch in the cell membrane (Mechanoreceptors).
2. If the stimulus is effective and triggers above threshold (-55mV) it will
cause a dramatic change within the membrane potential, voltage gated
Na+ channels will now open in response.
3. Na+ voltage gated channels open and depolarize the cell, making it
more positive. The cell is stimulated and the signal is propagated
throughout the cell.
4. Na+ channels close and K+ voltage gated proteins open. K+ flows
down its electrochemical gradient. This is known as repolarization as the
cell loses it positivity and approaches back to a negative cell membrane
potential.
5. K+ voltage gated channels tend to be slow and sluggish and remain open
a tiny bit longer than Na+ channels. This causes the cell to hyperpolarize
or become more negatively charged in comparison to the resting
membrane potential.
6. Na+/K+ pump and Leaky channels work together to restore the resting
membrane potential. Ions flow down back their concentration gradients
and the Na+/K+ pump maintains the resting cell membrane potential.

 Absolute Refractory Period

The absolute refractory period is a period during depolarization where
+
Na channels are unable to be re-activated or stimulated more than once. As Na+
voltage gated channels open to rapidly depolarize the cell and make the
intracellular more positive, they are unable to be stimulated again as the
membrane potential must return to a negative resting state before being
stimulated again. This period of inactivity is known as the absolute refractory
period.
Relative Refractory Period

From the absolute refractory period, it logically leads on to the relative

refractory period. This a period where K+ channels have now opened and
repolarization of the cell is occurring. In the absolute refractory period the
cell is unable to be stimulated again until the Na+ channels reset. In the
relative refractory period these Na+ begin to reset and can be stimulated only
under special circumstances. These circumstances require a strong stimulus
for the Na+ that have reset (relatively few) to reopen again. This period in
which the cell is repolarizing is known as the relative refractory period.

4. Propagation of Action Potential

There are two main types of how neurons conduct action potentials down their
axons.
Saltatory Conduction (Majority)
Saltatory conduction within neurons is a evolved biological advantage
that allows action potentials to move down axons at a fast rate.
Oligodendrocytes wrap neuronal axons in Myelin the CNS and
Schwann Cells that wrap neuronal axons in the PNS. Myelin sheath is
a insulating lipid substance that allows the signal of an action potential
to jump from Nodes of Ranvier along the axon. These gaps or
nodes are concentrated with Na+ and K+ voltage gated ion channels.

Rate = 100m/sec
Continuous Conduction (Minority)
Continuous conduction involves no myelin sheath (un-myelinated)
around the axonal membrane. They propagate down the axon via a
continuous amount of Na+ and K+ channels down the length of the
axon. It is considered much slower than Saltatory Conduction.

Rate = 10m/sec
What influences the rate of conduction?
The Diameter of the Axon Larger axons conduct faster
Myelinated or Un-myelinated eg: Saltatory or Continuous
Temperature Rate is significantly decreased in colder temperatures

Concluding Remarks on Action Potentials

They way Neuroscientists believe neurons speak or communicate
is via action potentials and the diverse frequency of the action
potentials.

 Action potentials can not be categorized as small or big they are

the all or nothing principle. However, the frequency of the action
potentials is interpreted by the CNS and responded to.
The action potential involves the maintenance of the Resting
Membrane potential via the Na/K Pump that maintains a high
concentration of K+ inside the cell and low concentration of Na+.
Other channels that help maintain the membrane potential involve
leaky channels and ion channels.
An action potential is initiated by a stimulus such as ligand activated
proteins, mechanoreceptors and cause Na+ voltage gated channels to
open and depolarize the cell. The action potential propagates down
the cell from the Axon Hillock to the Synaptic Cleft. Na+ channels
close and K+ channels open to repolarize the cell. K+ are a delayed
stimulus and are also relatively slow at closing causing a
hyperpolarization of the cell. Na/K pump reestablishes the resting
cell membrane potential (-65mV)
Neuronal cells contain two types of conduction; Saltatory
(Myelinated) and Continuous (Un-Myelinated).
Axonal diameter, temperature, myelination and type of
conductance effect the rate of conductance in neurons.

 Interestingly, the sodium voltage gated ion channel contains some

unique properties when compared to the potassium gated channel. The
Na+ channels has two Gates within its protein structure. The
Activation gate and the Inactivation gate. When initiated, the
activated gate (hence its name) opens as well as the inactivated gate.
Sodium rushes into the cell until the inactivated gate (ball and chain)
reacts and suddenly snaps shut to stop the flow of Na+. The
inactivation gate is very fast and responds well.
Review Questions

Answer
A) No net movement as the cell is in a equilibrium state with the K+.
K+Inside = K+Outside
B) K+ will move to the extracellular matrix due to the concentration and
electrical gradient.
C) K+ will move to the intracellular matrix.

Answer: True, chemically gated ion channels will only respond to a

hormone or neurotransmitter to trigger the channel to open to intern create a
action potential whos role is give to the voltage gated ion channels.

Lecture 3 - Synaptic Transmission

Objectives
Discuss information Transfer at the Synapse
Describe the types of Synapses
Discuss the principles of Chemical Synaptic Transmission
Understand its importance in studying drug action/effectiveness ,
interactions with neurotransmitters and other cell mediators
Compare normal to abnormal synapses
1. The types of Synapses
2. Principles of Chemical Synaptic Transmission
3. Synaptic Integration

1. The types of Synapses

A synapse is a specialized junction where one part of the neuron
(axon) contacts and communicates with another part of a neuron or
other cell type. Eg: The Neuromuscular Junction, (Neuron Muscle)
Electrical Synapses

Electrical Synapses are also known as gap junctions. They are cells
in which they are connected via protein channels called connexins
which make up a connexon. Two connexons join from each cell
membrane connect the cells and allow ions to pass through
bidirectional.
Gap Junctions allow cells to communicate in a cascade fashion and
synchronized harmony. A PSP (Post Synaptic Potential) allows these
cells to integrate and simultaneously depolarize. Eg: Cardiac cells
within the heart.

Chemical Synapses
The most abundant type of synapse are chemical synapses which are
found in CNS and PNS.

Chemical Synapse uses a messenger known as a Neurotransmitter.

Pre-synaptic Element:
The presynaptic element is where neurotransmitters are stored in vesicle
structures. The presynaptic contains the active zone where vesicles fuse with the
membrane and release the messengers into the synaptic cleft.
Membrane differentiations
Active Zone: Where the neurotransmitter vesicles + Ca2+ channels are
found.
Synaptic Density: Where a concentration of receptors reside.
Synaptic Vesicles
The vesicle structures that concentration neurotransmitters into a little ball
which fuses with the pre-synaptic membrane to then be released
Receptors
Neurotransmitters bind to the receptors found on the postsynaptic density.
Post- Synaptic Element
Action potential causes the release of a neurotransmitter from the presynaptic
element to the post synaptic element where the information is interpreted.

Geometry of Synapses

Axodendritic:
Axon connected to dendrite
Axosomatic:
Axon connected to the soma of the cell
Axoaxonic:
Axon connected to another axon
Dendrodendrictic : Dendrite to dendrite
CNS Geometry
Grays I (asymmetrical)
Excitatory synapse
Grays II (symmetrical)
Inhibitory synapse

The Neuromuscular Junction (NMJ) - The First Synapse Found!

Neuron Muscle

 The NMJ is the biggest synapse in the body and is the most studied
and understood synapse. Ach is the neurotransmitter released by the
pre-synaptic element which is funneled from the active zone to these
folds at the junction.
Neuropharmacology is profoundly focused on these synapses as many
toxins are able to block the receptors for Ach and intern cause
muscular paralysis.
2. Principles of Chemical Synaptic Transmission
1. Neurotransmitters (amines, amino acids and peptides) are synthesized
either at ER or onsite at the pre-synaptic element.
2. Neurotransmitters are packaged into vesicle structures and await
deportation at the active zone.
3. Action Potential causes the depolarization of the cell in which
reaches the pre-synapse and causes Ca2+ to open.
4. Vesicles fuse with the active zone and are released into the synaptic
cleft.
5. Neurotransmitters attach to receptors on the post-synaptic density
area and cause electro/chemical response to post-synaptic cell.

6. Neurotransmitters removed or broken down from the synaptic cleft.

Neurotransmitters
40 known kinds of neurotransmitters so far.
Can be broken down into three main groups based on their structure
Amines
eg: Dopamine, acetylcholine, Histamine, Serotonin
Amino Acids
Eg: Glutamate, Glycine, GABA
Peptides (large)
Eg: Cholecystokinin (digestion transmitter), Thrytropin (thalamus)
Dales Principle Stated that one neuron was responsible for one
neurotransmitter release, today we now know that this is not the case
Co-factors Neurotransmitters can be released with a peptide + amino acid or
amino acid + amine for example.
Neurotransmitters Synthesis and Storage

Peptides Are synthesized from a precursor in the Rough

Endoplasmic Reticulum and transported to the Golgi Apparatus where
it is activated and taken to the pre-synaptic terminal.

 Amino Acids/Amines Made by neurons that release them.

Synthesized onsite at the axon terminal by specific enzymes and ready
to be deported.
Neurotransmitter Release (Chemical Synaptic Transmission)
1.
Action potential arrives at synapse.
2.
Ca2+ channels open and influx of Ca2+
occurs.
3.
SNARE proteins merge vesicles to the
active
zone of the pre-synaptic membrane.
4. Neurotransmitters released into the
synaptic cleft.
5. Density area full of receptors
binds with neurotransmitter.
6. Neurotransmitter
degradation/ removal.
7. Endocytosis of vesicles
8. Post-Synaptic AP

Neurotransmitter Receptors
POST-SYNAPTIC
MEMBRANE
Ionotropic
VERY FAST TRANSMISSION
Spans the width of the post-synaptic membrane
Opens by stimulation of neurotransmitter
Unlike Na+ and K+ voltage gated channels as it
allows both Na and K to flow in, it is not as specific.
Stimulates both IPSP and EPSP
Metabotropic (G proteins)
Metabotropic Receptor

(Metabo = Metabolic)
SLOWER/LASTING
TRANSMISSION in the
POST SYNAPTIC
NEURON
Metabotropic have more
diverse functions in
comparison to Ionotropic
receptors.
They are activated by a
specific neurotransmitter
(1st Messenger) and are
linked to a
GProtein which can open a ion
channel or
produce a 2nd Messenger (cAMP)
that can run off into the cytosol and cause a cascade of effects.
EPSP and IPSP

Excitatory Post Synaptic Potential (EPSP)

Pre-synaptic release of neurotransmitters to post-synaptic membrane
receptors that cause a short positive influx to the PS Brings it closer
to a Action Potential
(eg: Ach and Glutamate gated ion channels)
Inhibitory Post Synaptic Potential (IPSP)
The release of a pre-synaptic membrane neurotransmitter to the postsynaptic membrane where it binds to its receptor but causes Cl- to
come into the cell and hyperpolarize the cell taking it further away
from the membrane threshold, thus inhibitory.

(eg: GABA, Glycine gated ion channels)

Neurotransmitter Recovery
Simple diffusion of neurotransmitter away from synapse
Enzymatic breakdown of neurotransmitter
Re-uptake of neurotransmitter via endocytosis
Desensitization of neurotransmitter:
o If a neurotransmitters presence is too long the receptors will
automatically close, therefore de-sensitizing the effect of the
neurotransmitter.
Neuropharmacology
Agonists : Drugs that mimic a particular neurotransmitter, eg a patient
is lacking Dopamine, synthetic drugs are made to mimic the naturally
occurring neurotransmitter to bring its levels up.
Antagonists : Block the receptors for neurotransmitters or stop their
function. Eg: Toxins that block Ach receptors causing paralysis.

NEUROTRANSMITTER PROBLEMS ARE THE ROOT CAUSE OF MANY

DISEASES AND DISORDERS
3. Synaptic Integration
The postsynaptic membrane integrates the complex ionic and
chemical interactions that arise from a large number of receptors.
This is known as Synaptic Integration. In other words, putting it all
together at the Post Synapse after a AP.
Quantal analysis Used to determine the amount of a NT released to
receptors
Eg: CNS release of one NT vesicle = a few tenths of a millivolt whilst the
PNS such as NMJ releases hundreds of NT vesicles to cause a huge change in
the membrane potential (40mV).
EPSP Summation
EPSPs are graded potentials that occur at the post synapse. These are mostly
occurring in the CNS as it allows variation and a myriad of responses.
Compared to the NMJ where big releases of NT (Ach) from a fully propagated
AP to allow it.
Spatial and Temporal Summation

a) Spatial summation is the adding together of EPSP from a axon to a dendrite

shown in diagram a. The EPSPs add on together from synapses generating
EPSPs simultaneously and increasing towards threshold.
b) Temporal summation is the consecutive stimulation of EPSPs from the
same synapse. They look like little jumps on a diagram.
Dendritic Properties
Dendrites arent as straight forward as one would perceive. They actually can
contain differing properties due to where they are located and their function.
They contribute to synaptic integration by properties much like a leaky hose.
Leaky Hose analogy.
Dendrites when stimulated by a EPSP creates the influx of positive
charge. This charge will propagate down the dendrite but
exponentially weakens from the area of the EPSP. This exponential
decrease is due to distance as charge dissipates across the membrane.
Imagine a hose with small holes in it. The water (positive charges) can
go two ways. Down the hose and through the leaks.

We can evaluate that much like a leaky hose, the water that runs from the source
to the end will be much less or non at all due to the leaks. This is how some
dendrites function.
Dendritic length constant ()
The dendritic length constant, mathematically shows how the depolarization at a
dendrite exponentially decreases over distance. As when a the post-synaptic
membrane potential will propagate towards the axon hillock but if the signal
is too weak when it reaches, it will not cause a action potential.
Excitable Dendrites
Some dendrites have characteristics in a way they are more
excitable. Passive dendrites will receive a signal from a presynaptic neurotransmitter and transfer the signal along the inside the
cell, but as we know it exponentially will decay if a weak signal.
Active Dendrites contain voltage gated ion channels such as K, Na
and Ca2+ to allow them to amplify the signal and intern increase the
chances of a AP.
This also allows a signal to travel along in the other direction, from
the soma, along a dendrite and to a axon. This is to inform the
neighboring cell that a spike has occurred in the soma and is a key
property in learning.

IPSPs and Shunting Inhibition

Neurotransmitters contain a specific system and function. Some

neurotransmitters are inhibitory (GABA) and some neurotransmitters
are excitatory (Glutamate).
The Shunting inhibition is a property in neurons used to inhibit the
excitatory effect of a neurotransmitter before it reaches the soma and
has the potential to cause a depolarization. For example, a glutamate
synapse excites the post-synaptic cell and travels down the dendrite
towards the soma. Before it reaches, another synapse fires and releases
a inhibitory NT such as GABA to inhibit the signal or draw it away
from the threshold, making the cell less likely to fire a AP.
Excitatory NT(Glutamate) Na+ into the cell and K+ out
Inhibitory NT (GABA)
Cl- into the cell
Excitatory Neurons/Inhibitory Neurons
Excitatory Neurons (Gray I) : Include neurons that synthesize, store
and release a specific neurotransmitters that causes a excitatory effect in PSM.
Glutamate is common excitatory NT. Excitatory Neurons are considered CNS
Gray I and are asymmetrical in their membrane differentiations (Active area
and post synaptic density are)

Inhibitory Neurons (Gray II): Include

neurons that synthesize, store and
release inhibitory NT such as GABA or
Glycine, which causes Cl- ion channels to
open and push the membrane potential away
from the threshold. They are called CNS
Gray II and contain symmetrical
membrane differentiations.
Modulation (Modifying a Signal
G Proteins)
The process of modulation
isnt related to transmitter gated
channels where the
neurotransmitter binds to a specific
subtype of transmitter
gated channels and
opens the pore. Instead it
is related to G proteins that allow modification of the EPSP.
G-Proteins allow more options to the post synaptic cellular response.
In that it could be linked to a ion channel or could produce something
else such as a cascade effect.
Modulation therefore modifies the EPSP that were generated by
other synapses. A example of G-protein coupled receptor is the
norepinephrine B receptor.

 MORE OPTIONS
The NT norepinephrine attached to the norepinephrine receptor
(G-protein).
1. The G-protein located intracellular is activated to stimulate Adenylyl
cyclase (Enzyme) that dephosphorylates ATP to cAMP a secondary
messenger that can diffuse off into cytosol to create a cascade of effects.
2. In the context of the norepinephrine receptor, the cAMP runs off to
find a protein kinase (on/off) that phosphorylates the K+ channel to
change its conformation and CLOSE.
3. The closing of the potassium channel increases the excitability of the
cell (as no K+ is leaking out) and therefore increases to chance of the cell
to depolarize.
1st Messenger: Norepinephrine (Neurotransmitter)
2nd Messenger: cAMP
G proteins are not channels as you can see when theyre activated they
do not open. They can indirectly open a channel or produce a 2nd
Messenger to cause a cascade of effects within the cell.

 The G-Proteins therefore modulate or modify the EPSP or IPSP to

create OPTIONS.
Options that might induce a inhibitory effect or excitatory effect, open
or close channels or cause a cascade of intermediate reactions and
products within the cytosol.
The Secondary messengers in G- proteins, phosphorylation and the
activity of protein kinases (enzymes that switch things on and off) are heavy
related to learning and memory.

Neurotransmitters Lecture 4

Criteria for a Neurotransmitter System to be identified.

 Neurons must synthesize and store the neurotransmitter within the cell
Neurotransmitter must be released at the axon terminal when
stimulated.
Neurotransmitter must bind to a receptor protein in the post synaptic
element.
Degradation of Neurotransmitter (recycled).
DALES PRINCIPLE
One neurotransmitter, one neuron. Usually neurons synthesis one
type of neurotransmitter and secrete one type of transmitter. Cofactors are a
exception. (Peptide + amino acid)
Estimated 107 (Billions) Neurons and 1014 (Trillion) Synapses in the
human body Explains their diverse functions and range
How do we identify a Chemical as a neurotransmitter?
If there is a hunch a chemical might be a neurotransmitter a scientist can
perform the following to find the proof.
Immunocytochemistry
Reacting a anti-body to bind to the chemical to find where in the cells the
chemical is.
In Vitro Brain slices
Bathing particular segments of the brain in solution and stimulating it to
see what chemical is released into the solution.
In situ Hybridization
Complementory mRNA to attach itself to ssRNA used to synthesize the
chemical or receptor.
Microionophoresis
Selecting a compound that mimics the theorized neurotransmitter and
seeing if it attaches to the same receptors.
(nicotine/muscarine mimic Ach neurotransmitter)
Neuropharmacological Analysis
Using drugs on specific synapses to see their effects on the receptors. Eg:
Curare is a agonist of nicotinic receptors, causing paralysis .
Ligand Binding
The use of a radioactive isotope to bind to a ligand molecule
(neurotransmitter) to see where it attaches onto what receptors.

Agonist A compound that mimics the characteristics of a

neurotransmitter. Eg: Nicotine and Muscarine are synthetically made drugs
thats mimic Ach. Nicotine receptors found in muscles and muscarine found in
heart.
Antagonist A compound that blocks a neurotransmitters receptors.
Eg: Curare is a poisonous compound that blocks Ach receptors, causing
paralysis.

Neurotransmitter System - what do they require?

The Molecule
Acetylcholine
Synthetic machinery (enzymes) Choline Acetyltransferase (ChAt)
Packaging
Vesicles (granules are for peptides)
Degradation
Acetylcholinesterase (AchE)
Reuptake
channels to reuptake choline+ acetyl CoA
Suffix - ergic Relating to a group of neurotransmitters
Cholinergic Neurons (Fast Synaptic Transmission)
Neurons that synthesize Acetylcholine Neurotransmitter
(Excitatory &Inhibitory)
Acetylcholine binds with nicotinic and muscarinic receptors.
Agonists of Cholinergic neurons are nicotine and Muscarine.
Nicotine binds to nicotinic receptors found in the muscles, whilst
muscarine is a inhibitory agonist of acetylcholine in lowering the heart rate.

synaptic
(AchE).
motor
and has
muscle
effect and
in the

Acetylcholine is derived from Acetyl CoA

and Choline and bound
together using Choline
Acetyltransferase (ChAT)
and broken down in the
cleft by Acetylcholinesterase
Ach is synthesized by all
neurons in the axon terminal
common receptors found in
the heart and skeletal muscles.
Nicotinic receptors found in
cells/NMJ as an excitatory
Muscarinic receptors found
heart that is inhibitory.

(ChAT) Good marker for locating Cholinergic Neurons

Catecholaminergic Neurons
The Catecholamines are derived from the precursor and amino acid
Tyrosine and all contain chemical group called a Catechol. Catecholamines
include
Dopamine
Norepinephrine
Epinephrine
Catecholamines are important in the regulation of movement, mood
(reward), attention and visceral function (ANS)
Catechol + amine = Catecholamine
Tyrosine (TH) is the derivative of all the Catecholamines that is, it is the
precursor to form Tyrosine Dopamine Norepinephrine Epinephrine
Tyrosine Dopamine
Dopamine is a major neurotransmitter is the CNS for the control of mood
in terms of rewarding mood behaviors and in motor control. A common
degenerative disease called Parkinsons Disease is due to the degeneration of
Dopaminergic neurons. Treatment includes using Dopa enzyme to increase the
levels of Dopamine within the remaining dopaminergic neurons.
Symptoms of Parkinsons is shown in shaking motor control or tremors.

(MAO) is the destructive enzyme that

breaks down catecholamines.

release

Tyrosine -( Tyrosine Hydroxylase) Dopa (Dopa

Decarboxylase) Dopamine
DBH) Norepinephrine (PNMT)
Epinephrine
All broken down by the enzyme MAO
Seretonergic Neurons
This is the Neurons related to the
of Serotonin neurotransmitter.
Regulates mood, emotional behavior and sleep.
Serotonin is derived from
Tryptophan that is obtained through

diet.
Serotonin made in two steps
Tryptophan(TP) (Tryptophan

1.
Hydroxylase) 5 -HTP
2.
Serotonin

5-HTP

(5 HTP Carboxylase)

Low Serotonin as it controls the regulation of emotional behavior can

lead to clinical depression. Fluoxetine Prozac is given to patients to prolong the
effect of Serotonin and thus are anti-depressants.
(MAO) is the destructive enzyme that breaks down Serotonin.
Amino acidergic Neurons (Fast Synaptic Transmission)
Are all amino acids and include Glutamate, Glycine and GABA and
are well known for their fast synaptic transmission
Glutamate (Glu) - Excitatory Neurotransmitter
- AMPA and NMDA receptors
Represent most of the bulk of fast synaptic transmission.

AMPA Glutamate binds to AMPA that allows both K+ and Na+ to pass
through, therefore creating a rapid depolarization.
NMDA Requires Glutamate + Glycine to bind to but also the removal of
Mg++ that clogs the pore of the ion channel. Mg++ (the bouncer at the night
club) doesnt allows any of the permeable ions to flow through which are Ca++
and Na+.
Only depolarization of the membrane will unbind Mg++ by losing its affinity
from the pore and allow Na and Ca++ to flow through.
(NMDA channels are linked to long term memory)
AMPA Binds Glutamate Na+ into post synapse Fast
Depolarization
NMDA Blinds Glutamate Mg++ blocks and becomes voltage
dependent
G

Depolarization of the membrane allows Mg++ to unblock pore

and allow Ca++ and Na+. Glutamate needed to be bound as well.

Glycine (Gly) and GABA

Inhibitory Neurotransmitters
GABA and Glycine are
considered major inhibitory NT
in the CNS as they act on ionotropic Clchannels that cause a hyperpolarization of the cell IPSP
GABAergic Neurons (Inhibitory)
GABAA Receptor : Binds to ionotropic ligand channel and opens Clchannels to hyperpolarize the cell, thus inhibitory.
GABAB Receptor: Binds to metabotropic ligand channel which is
linked to a G-Protein that hyperpolarizes by opening K+ channels and
allowing them to flow outwards, thus hyperpolarizing the cell.
Glycine Neurons (Inhibitory)
Acts on ionotropic Cl- channels that hyperpolarize the cell, thus
inhibitory
Works with GABA to cause inhibitory effects.

The beauty of neurotransmitters is that they can change from one major
excitatory NT such as Glutamate (EPSP) to a major inhibitory NT GABA
(IPSP) in one step. GAD enzyme transforms Glutamate GABA

G- Proteins/2nd Messengers ARE AMAZING!

G-Proteins are unlike ionotropic ligand channels in which a
neurotransmitter binds and activates a channel to open.
G- Proteins produce slower, longer lasting and diverse effects in
the cell via a 2nd Messenger, they do this by more complex means of
altering the biochemistry of the cell. Linked to memories/learning

G Proteins are named by the energy molecule that they utilize, GDP which is
a derivative of ATP and when activated by its particular NT, goes from GDP
GTP and causes the G-Protein to split and activate subsequent proteins
downstream or effectors. The shortcut pathway of G-protein is that it doesnt
have many intermediates for it to start working, enabling it to work faster. The
major difference between G-Proteins and ionotropic ligand gated channels is
that they produce a secondary messenger, usually in the form of GDP that runs
off into the cell and can activate a cascade of events. A common event is that it
can activate Protein Kinases (switch things on/off) that phosphorylate (switch
on) proteins to change their conformational shape eg: ion channel. Protein
Phosphatases are enzymes that switch off the or inhibit the effect of protein
kinases which de-phosphorylate the protein.
Kinases Phosphorylate (switch things on)
Phosphatases

dephosphorylate
(switch things off)

Example
1. NT arrives and attaches to its receptor
2. GDP is exchanged for GTP
3. GTP splits/activates the segments that runs along the Post synaptic
membrane to effectors
4. Section of the G-protein gates a K+ than allow heart rate to reduce.

 G-proteins can be inhibit or activate adenyl cyclase, in other words a NT

can come along and activate a G-Protein that may inhibit an affect of another Gprotein that might be activating adenylyl cyclase to produce a cascade of events.
The Push or Pull

An example of the effects of G-Proteins as one NT activates a G-protein

GDP GTP and splits off to activate adenylyl cyclase that converts ATP to
cAMP (another secondary messenger) that will run off into the cytosol and
activate Protein kinases that will phosphorylate K+ channels. You can see its
a exponential effect, thus G-Proteins have a slower, longer lasting and diverse
effect compared to ionotropic channels .
Divergence and Convergence

Divergence is where a single Neurotransmitter can activate a diverse

range of receptor subtypes that intern can have multiple functions or
effects.
Divergence One neurotransmitter having diverse effects by
attaching to different receptor subtypes.

Convergence is where separate neurotransmitters that bind to their

own independent subtype receptors but end up effecting the same
thing or producing the same effect as another neurotransmitter can do.
Convergence Converging of different neurotransmitters to have
the same effect
Somatosensory System Touch

The somatosensory system is involved with touch and pain

regulation of the body. The systems of touch and pain are separate.
The somatosensory system primarily uses mechanoreceptors on the
sensory neurons. Mechanoreceptors open in response to stretching or
bending due to physical distortion.
Different types of sensory neurons respond differently to different
stimulus such as vibrations, temperature, pain.
At the heart of each mechanoreceptor neuron are unmyleninated
axons as these are jam packed full of mechanosensisitve channels.
The Skin
You have two types of skin on the body.
o Hairy
back of palm
o Glabrous ( Hairless)
the palm
st
1 Layer Epidermis
2nd Layer Dermis
Pacinian Corpuscles (Dermis) Large receptive field Rapid
Adaption

 Are found deep in the dermis layer and look like onions. They have
large receptive field and adapt (stop depolarizing) to sense quickly
Meissners Corpuscle (Dermis) Small Receptive field Rapid
adaption
Are found in the dermis, have a small receptive field and adapt fast

The diagram depicts` how two individual sensory neurons have

different receptive fields.

Pacinian Corpuscle Large receptive field Fast Adapting

Meissners Corpuscle Small Receptive field Fast adapting
Merkels Disks
Small receptive field Slow adapting
Ruffinins ending
Large receptive field Slow adapting

 So.Why do Merkels disks and Pacinian Corpuscles differ in receptive

fields?
Two Point Discrimination
The two point discrimination test is testing the co-ordination of somatosensory
cortex and also the mechanoreceptors found all over the body. You would
realize that some areas on your body are more sensitive such as your lips, your
tonugue and fingers. The reasons why are :
Receptor field Density
There are a higher concentrations of mechanorecpetors in areas
that are more sensitive such as the lips, fingers and soles of the feet.
Receptor field size
Areas such as the fingertips and hands contain mechanoreceptors that
have a small receptive field (Merkels disk and Messians corpuscle).
Notice if you un-ravelled a paper clip into a U shape and placed it on
your finger tip, you can discriminate the two points.
Computing Power
Areas of the brain (somatosensory cortex) which are devoted to areas
on the body. For example, the somatosensory cortex has areas that are
larger or more devoted to high density neuron areas such as the hands,
lips and feet. Areas such as the legs and thoracic have areas less
devoted.
Special Neuronal Mechanisms
It may be possible that there are special neuronal mechanisms in the
body that create a higher resolutlion to more denser mechanoreceptor
areas.

.
Diagram showing the minimum distance needed to discriminate between
two points on the body.
A, A, A and C axons Primary Afferent Neurons

Primary afferent Neurons

Afferent neurons, are sensory neurons leading from the sensory organs (skin) to
the dorsal root where it is shot up to the brain and interpreted. The afferent
neurons that produce the signals have axons that vary in shape and size and
directly relate to their function.
Large diameter + mylenated = fast transmission
Proprioperception Sensory information for awareness of where limbs are,
muscle status.
A Large diameter, myelinated. Proprioreceptos of the muscles need to be
fast to give continuous feedback on muscle status and location.
A Larage diameter, myelinted and fast transmission. Mechanoreceptors
usally have them to transmit fast signals
A and C Notice they are slower in transmission, these are largely
associated with pain and temperature regulation.
START

Cervical cord (C1- C8)

Thoracic cord (T1-T12)

Lumber cord (L1-L5)

Sacral cord (S1-S5)

Total = 30
END

Dermatomes : Dermatomes are the areas of sensation covered by each

spinal segment. For example C2-C5 cover the sensory areas of the neck down to
the arms and fingers.

.
Diagam relevant to evoultionary traits, dermatones are linearized
when we get on all fours (like our ancestors)
A single spinal segment consists of the dorsal root (afferent) and
ventral root (efferent) covers an area on the body.
The
communication between the area and spinal
segment is known as a Dermatome.

The Dorsal Column

Medial Lemniscal
Pathway (PNS)
Touch and and
Pain follow different
pathways in the
CNS. Information
relating to touch or vibration of the skin ascend up the dorsal
column.
The Dorsal Column is mainly composed of A axons.

 The stimulus shoots up the dorsal column (A axons) and reaches

the dorsal column nuclei at the medulla when it switches over in
direction by the medial lemniscus
The medial lemniscus is the reason why your right side of your body
is interpreted by the left side of your brain. It acts as a little bridge.
From the medial lemniscus the signal reaches the Thalamus/VP
nucleus (relay station of the brain) and is diverted the
somatosensory cortex (S1).
Mechanorecpetor Dorsal Column Medulla (dorsal column
nuclei) Medial Lemniscus (bridge) Thalamus/VP Nuclues (relay)
Somatosensory (S1)

The Trigeminal Pathway (Face Sensation)

The Dorsal Column Medial Lemiscus Pathway is associated with
the spinal cord and everything that differentiates off of it. If this was
the full story, your face would numb!! So the Trigeminal Pathway
is key to feeling sensations all over your face.
Mechanorecpetors are innervated all over the face including, lips,
tongue, skin ect..
Stimulus from mechanoreceptors follow along the Trigeminal
nerves that connects to the pons
Synapse onto the Trigeminal Nucleus and are relayed at the VP
nucleus/thalamus, divert off to the S1 (Somatosensory Cortex)
Mechanorecptor Trigeminal Nerve Pons Trigeminal Nucleus
Thalamus/VP nucleus S1 (Somatosensory cortex)

Somatosensory Cortex (S1)

Somatosensory Cortex (S1) The Cortex for the Somatosensory
system.
Area 3B is associated heavilywith touch sensation beause
o It receives dense input from the VP nucleus at the Thalamus
o The neurons are highly excitable to touch sensations
o Lesions to this area cause loss of sensation
o Electrical stimulus evokes sensations (epilepsy) People after a
epilepsy attack they say they couldnt feel or could feel things
touch them.

 Area 3A does receive input from somatosensory information but is

more associated to proprioception, which is the feeling of ones own
limbs and location/status of the extremities.

Area 3B Primary Somatosensory cortex

Area 1 Is associated with texture information some as the feeling of
a surface, if it is rough, smooth, sharp
Area 2 Is more associated with shape and size of objects.
Posterior Parietal Cortex
Associated with a blend of visual communication, somatic sensory
and movement planning.

to

their own

Neglect Syndrome
Where a person neglects a part of
their body or a part of the world. Due
lesions in the areas of the Postier
Parietal Cortex are related to
neglect syndrome. For example a
person might disregard their arm as
arm, or dress only half the body
because they dont believe the other half is
theirs, or neglect everything to the left of
their central vision.
VERY BIZZARE BUT INTERESTING
NEUROLOGICAL DISORDER!!

Somatic Agnosia (the inability to

discriminate/recognize things)
A person finds it hard (with no
visual conformation) to
discriminate between the shape and
texture of objects say in their pocket. Eg: the difference between
their car keys and a pack of chewing gum.
Other forms of agnosia are time agnosia, auditory agnosia, visual
agnosia.
Cortical Somatotopy
Areas of the Somatic Sensory Cortex (S1) that are devoted to parts of
the body.
Soamtotopy is the relationship of the area within the somatosensory
cortex and the sensory area on the body. Larger portions of the
somatosensory cortex are devoted to finely tuned, high neuronal
sensory density areas such as the hands, feet, face, lips and mouth.

Cortical Plasticity (Neuroplasticity)

Originally it was thought the bain was a static organ. Now it is seen
that brain is continuously evolving/adapting.
Certain segements of the brain can become more devoted to a specific
function over time.
An example of cortical plasticity is shown in the experiment of an
owl monkey. The areas in the somatosensory cortex were mapped
directly to each other fingers. When one finger was amputated it was
shown that the original area devoted to the sensation of that finger are
merged with the surrounding areas, giving rise to the other fingers
having more computing power/sensation.

 Another example of cortical plasticity or neuroplasticity is shown in

musicians who play string instruments. Musicians tend to have larger
areas devoted to the fine motor control (primary motor cortex) and
tuned sensation (Somatosensory cortex). Mostly due to the continuous
stimulus of using the left hand.

 will drop box sync this file?

Somatosensory System - Pain

Pain The perception or feeling of irritation, burning, stabbing,
irritating, sore sensations.
Nociecption The transduction pathway of pain from nociceptors. How
the somatosensory distuiguishes pain from touch.
(Transduction) The change of physical energy, to chemical energy, to
electrical energy.
Hyperalgesia : Heightened pain response (increased sensitivity)
Hypalgesia : Lowered pain response (afferent regulation of pain)
Analgesia : Absence of pain
Types of Nociceptors
Nociceptors refer to the branch of neurons that sense, regulate and
trasndude pain. They are polymodal in that they differ by being more sensitive
to certain stimuli.
Thermal Nociceptors
burns or extreme cold
Mechanical Nociceptors strong pressure, breaking of skin
Chemical Nociceptors respond to compounds released when
trauma is sustained eg: Bradykinin, Prostaglandins, K+, Histamine.

Hyperalgesia
The increased sensitivity to pain. A regulated mechanism to let us know that that
area (muscle, bone) is damaged or potentially being damaged. The increased
sensitivity of pain is hyperalgesia. In other words, if you poke a person who
has surffered a 3rd degree burn, it fucking hurts.
Substances are released when tissue damage occurs
Nociceptors respond to these
o K+, Bradykinin (directly depolarizes nociceptors)
prostaglandins (by products of enzymatic lipid breakdown),
Histamine (hormone that inflames area) and Substance P
which is produced from the actual nociceptors themselves.
Substance P
A peptide synthesized by C fibres themselves to communicate with other
nociceptors and cause vasodilation of the blood vessels.
Nerve Axons

 Slow pain (throbbing)

Un-myelinated
Glutamate and Substance P

Pathways of Pain (Afferents)

Spinothalamic Pathway
Trigeminal Pathway
Spinothalamic Pathway

Fast Pain (Thumbtack)

Myelinated
Glutamate

Nocieptors linked by C fibres enter the Dorsal root

Trace into a area known as the Zone of Lissauer
Synapse onto the Substantia Gelatinso
Ascend up the spinal cord contralaterally (opposite side to
stimulus)

straight
opposite of

but

Second order neurons decussate

away and ascend up the spine
contralaterally.
(They ascend up the spine
the stimulus)
Spinothalamic pathway has no
more synapses until it reaches the
thalamus. Hence, the title The
Spinothalamic Pathway.

Touch Ascends ipsilaterally

( on the same side of the stimulus),
decussates at the medial
lemniscus which gives rise to
side of the brain is activated when you

why the right

touch something on yourself side.
Pain Ascends contralaterally (on the opposite side of the stimulus), thus it
decussates straight away and ascends.

(Decussates: Crosses over or forms a X shape)

1st Order:
First order neurons are
a sensory receptor.
2nd Order:
Second order is
in the dorsal root.
3rd Order
Third order occurs within

pre dorsal root ganglion. Such as

within the spinal cord, such as
the brain, usually within the
thalamus (relay).
Usually a synapse occurs when the neurons
jump up in order.

1
2nd
3rd

Order : Sensory
Spinal Crd
Order: Spinal Cord Brain
Order: Within the Brain
st

Brown Sequard Syndrome

In trauma to the spinal cord where only half the spinal is damaged,
specific deficits are shown. If a lesion forms on the right side of the
spinal cord, the patient will lose touch and vibration sensation on the
same side. On the other hand, deficits in pain and temperature will be
on the opposite side to the lesion. Due to the instant decussate nature
of the spinothalamic pathway and the opposite ascending pathways
(ipsilateral and contralateral).
Trigeminal Pain Pathway
Synapse onto 2nd order neurons in the spinal trigeminal nucleus of
the brain stem
Cross and ascend to the thalamus in the trigeminal lemniscus
At the Thalamus
The spinothalamic and trigeminal pain pathways synapse over a
larger area than the touch nucleus areas. Most of the touch neurons
end in the VP nucleus. Touch and Pain are still seperarted but pain
neurons terminate in the VP nucleus and Intralaminer Nuclei. T
THEY ARE STILL DISTINCTlY SEPERATED

Afferent Regulation
Gate Theory suggests that maybe neurons at the dorsal horns that
project axons up the spinothalamic and neurons that project up the
dorsal column are intercepted by a interneuron.
If large A sensory neurons are a excited they can possibly inhibit the
nociceptive neurons.

Descending Regulation
PAG (Periaqueductal Grey Matter)

o A nuclei of neurons in the brain known as the Periaqueductcal

Grey Matter (PAG) is known for its analgesic effect on parts
of the body.
o Electrical stimulation of this area of the brain causes profound
analgesia and is sometimes used clynically for pain.
o PAG has axons descending down into the medulla at Raphe
Nuclei where they project down to dorsal horns and are able to
suppress or turn down the excitability of the nociceptor

Opioids
The compound opium is found in many opioid substances that are
well known for their analgesi, sedative and euphoria effects.
Opium is the active ingredient in a lot of narcotics that are abused
Analogues include morphine, heroin and codeine.
Opioid substances bind tightly to opioid receptors that are originally the
receptors for the bodys own naturally opioid substances to down regulate pain.
Endorphines were found through the use of opioids.
Endorphines (Endogenous Morphine)
Endorphines are found throughout the CNS and relatively small
peptide proteins.

 Endorphines are widespreadly used in the body but are well known to
be the bodies natural morphine making compounds that can regulate
nociception
Endorphines systems can block the pre-synaptic terminals of
glutamate and hyperpolarize nociceptors. Intern preventing the
passages of signals ascending to the brain and prevent the perception
of pain.

Paleospinothalamic is a pathway mainly concered with the C fibres

that regulate slow pain. The paleospinothalamic pathway is more
concered with the arousal, mood and attention as the nerve fibres
teriminate in the reticular activating system (concerned with mood,
attention and arousal.

 Neospinothalamic pathway is regulated by delta fibres that are

concerned with fast pain. They directly terminate in the thalamus
and parietal cortex where the exact location and identification of the
pain can be determined.

An itch sensation travels along C fibres towards the brain. C fibres are mainly
concered with itch sensations, temperature and some pain unlike delta fibres
that are more associated with pain. The itch sensation depending on where it
is located will travel through the spinothalamic pathway to the thalamus and
relayed to the somatosensory cortex, assuming that the itch is peripheral and
not on the face. Otherwise, the itch sensation will travel along the trigeminal
pathway through the trigeminal nerves.

False. The paleospinothalamic pathway is more associated with mood,

arousal and attention. Identification of the pain is through the neospinothalamic
pathway.

2nd Order.
2nd order Neurons synapse the signal from the spine to the brain. 3rd order
neurons are located inside the brain and 1st order are sensory neurons located all
over the skin.
Gustatory (Taste)
Humans have inborn chemical sensations to alert us about something
that could be harmful eg: posions are usually bitter and things that are good for
us eg: sugars (simple carbohydrates) that are sweet
Bitter Poison Reject
Sweet Sugar Accept

Taste is mostly associated with the tongue but it is interrelated with

smell. Note that the nasal cavity is directly linked to the mouth and thus taste is
contributed by odors from the food.
Pharynx and Epiglottis contribute to parts of taste.

Taste Buds
Taste buds are
composed of around 50150 taste cells. These taste cells
are NOT neurons, but they do
synapse onto afferent neuronal
axons that lead off to the
brain.
Tastant Taste Cell
Depolarization onto Gustatory
Afferent AxonsNT released onto
Gustatory Afferent
Axons
Microvilli
form around the taste pore where
the tastants are received and bind to receptors on microvilli.
Basal Cells contribute to regenerating taste cells and secreting
mucous/saliva for the tastants to dissolve into.

The Apical end of the taste cell is a taste pore that is exposed to the
surface of the tongue. Microvilli are surrounding this area so that the
tastants can be detected and attach to the cell receptors.

 The actual neurotransmitter that is released when these cells

depolarize is unknown. We know it that is excitatory and it
depolarizes the gustatory afferent axons. (most likely glutamate)
Afferent Gustatory axons travel to the brain stem to the gustatory
nucleus (Medulla).
Types of Papillae
Papillae : The indivudal distinct structures that form different shapes
(Fungiform,Vallate and Floliate). They contain the taste buds which contain the
50-150 taste cells.
Fungiform Papillae
Spread all over the tongue, are small fungi looking taste buds
Vallate Papillae
Look like large pimples, mainly attributed to the back of the tongue
Foliate Papillae
Sharp ridges, mainly attributed to the sides of the tongue.

The Five Main Tastants

1. Sweet (Sugars G Pro)

2. Bitter ( G-Proteins)
3. Sour (H+ ions)
4. Salt (Na+)
5. Umami ( G proteins)
The combination and sensitivity of these
combined tastants causes unique tastes.
Umami is delicious and is
associated with a amino acid Glutamate.

Areas on the surface of the

tongue are more sensitive to
some tastants, they
tend to be stimulated
more by one particular tastant such as salt or sour. The areas most
associated with a particular taste are:
Back of the Tongue Bitterness
Tip of the Tongue Sweetness
Sides of the Tongue Sourness and Saltiness
The middle of the tongue is not very sensitive to particular tastes.
Taste buds can taste all of the five tastants but some have lower
thresholds to specific tastants, in other words they are more sensitive.
These are shown in the above diagram.
When the concentration of one tastant is high, taste receptors will
tend to then not be as picky into what tastant they prefer and
stimulate most to.
Eg: If I place a tablespoon of salt onto my tongue, a large amount of
the taste cells will depolarize. Even the ones that werent necessarily
sensitive to the stimulus. Aka Na+

Taste Transduction
Saltiness Na+ amiloride channel
Sourness H+ blocks K+ channel and uses Na+ amiloride channel
Bitterness (G protein T2Rs)
Sweetness (G protein T1R1 1 and T1R1 2)
Umami (G protein T1R1 and TIRI3)

Saltiness (Na+ influx)

Saltiness comes from the compound NaCl or things that contain the
ion Na+. It is mostly picked up around the sides of the tongue.
Na+ can directly enter the apical end of the papilla and diffuse
directly across the microvilli through a open Na+ channel. This
channel allows Na+ to flow freely down its concentration gradient into
the taste cells. It is known as the Na+ Amiloride channel.
Taste Cells reach threshold and open Ca2+ and Na+ voltage gated
channels to than release a neurotransmitter to gustatory afferent
axons..
Sourness (H+ influx)
Sourness occurs from H+ ions from acidic
compounds. It is mostly picked up along the sides of the
tongue
H+ ions flow into the apical end and cross the
microvilli of the taste cell from the surface of the
tongue.
H+ use the same Na+ amiloride channel as Na+, but
blocks the K+ channel of the cell, causing it to
depolarize faster and cause Ca2+ and Na+ voltage
gated channels to open.
Neurotransmitter is released to gustatory afferent
axons.

Bitter, Sweet and Umami

Bitter compounds such as caffeine and beer, sweet compounds such
as sugars like sucrose and fructose and Umami ( mostly associated
with glutamate) are all mediated by G- Proteins and follow a different
taste transduction pathway!
Bitter, Sweet and Umami have G-Protein Receptors located on their
microvilli. G-proteins are encoded by a variety of genes (possibly why
we have different opinions in tastes on food)
G- Proteins activate a 2nd Messenger called IP3

 IP3 is sent off into the cytosol and opens Na+ channels to depolarize
and also voltage gated Calcium channels depolarize.
IP3 can also activate intracellular stored Ca2+ that also can depolarize
the cell. Neurotransmitter is released to afferent gustatory afferent
axons.

G Protein Receptors for Sweet, Bitter and Umami

T1R1 + T1R2 Sweet Receptor (R2 and R3)
T1R1 +T1R3 Umami Receptor (R1 and R3)
T2Rs
Bitter
(Rs)

Taste Pathways
Nerves VII (7), IX(9) and X(10) bundle the gustatory afferent nerves
and terminate in the Solitary Nucleus of the Medulla.
VII Facial Nerve
IX GlossoPharagneal Nerve
X Vagus Nerve
Afferent Gustatory Axons Cranial Nerves VII,IX and X Solitary
Nucleus (Gustatory Nucleus) VMP (thalamus) Gustatory Cortex

Neural Coding of Taste

Population coding is the idea that each taste receptor cell is broadly
tuned. Although taste receptor cells usually are more stimulated by 1
or 2 tastants, they are still able to fire to other stimulates.
What gives every food nearly a unique taste?

Each taste cell is broadly tuned, their responses are combined into
afferent axons and a whole combinations of stimulus can be interpreted. This is
known as population coding, in that a broad range of neuron stimulus is
combined and the brain has a variety of stimulus to interpret.
Olfactory input also contributes as odors can stimulate and combine
with the taste along with the texture and feel of the food.
Olfactory Smell
Smell or our olfactory system is to help us distinguish and warn us
about good substances and bad substances .
Olfaction is associated with gustatory and provides us is with a more
thorough sensory detection mechanism.

3 Types of Cells
Olfactory Receptor Cells
These cells axons penetrate the cribriform plate and their axons link up
nd
with 2 order neurons called Glomeuri or a Glomerulus. These cells are actual
neurons unlike the taste cells in the gustatory system.
Glial Cells
Glial cells that support and nourish olfactory sensory neurons. They also
produce mucous that odorants dissolve in along the epithelial layer. Mucous
contains antibodies and enzymes to break down pathogens.

 Basal Cells
The unique thing about the olfactory system is that contain one of the few
types of neurons that continually renew themselves. Basal Cells, differentiate
into olfactory neuron cells constantly, as the receptor cells are very delicate.
Olfactory Neuronal Cells
One of the few types of neurons that can continually replace
themselves.
Very susceptible to damage, such as a blow to the cribriform plate can
break olfactory neuron cells and cause Anosmia.
Anosmia The inability to smell
Olfactory neurons have dendrites that end at a
knob in the mucous layer. Cilia
project into the mucous layer and are ready to be
depolarized by odorants.
Cilia within the membrane mainly
use a special type of G-Protein.
This G-Protein is known as Ggolf.
Olfactory neurons combine
to the olfactory nerve which bundles
to Cranial Nerve 1
Olfactory Transduction
pathway
1. Ggolf stimulated protein by ordorant
2. Adenyl Cyclase activates 2nd Messenger cAMP
3. cAMP activates cAMP activated channels (unusual)
4. Na+ and Ca++ channels open and depolarize the cell.
5. Cl- channels also open by Ca++ but expel Cl- from the cell causing a
BIG DEPOLARIZATION
6. Cranial 1 Nerve Olfactory Bulb

Ggolf Unique to the olfactory system

Transduction Termination
Odorants simply diffuse away
cAMP degrades and channels close
Enzymes break down odorants in the mucous layer
Unusual Traits of The Olfactory System
1. There are over 350 known Ggolf proteins. Thus there are 350 genes
being expressed at any one time. Each olfactory recptor neuron
expresses only one of the Ggolf G-Proteins within its cell
membrane. Therefore each neuron is a specialist at a particular
odorant.
2. cAMP is the only 2nd Messenger within the Olfactory
Transduction Pathway.

 Each Glomerulus links up to neurons that is expressing one particular

Ggolf protein that specializes in binding one particular odorant!
Olfactory Epithelium links up to 2 olfactory bulbs!
Central Olfactory Pathways

 Olfactory bulb projects into the thalamus where it can be relayed to

many higher order cerebral cortexs. This would explain how smell is
linked to the amygdala ( responsible to emotion), the hippocampus
(responsible for the long term memory) and of course the olfactory
cortex located in the TEMPORAL LOBE where a lot of the
processing of smell is interpreted.

Gustatory and Olfactory Cortex located in the temporal lobe.

Theories of Representation of Olfactory Information

 Population Coding
Similar to Gustation, in that specific populations of neurons that are
broadly tuned to one stimulus to be interpreted by the brain a specific odor. The
combination of this specific stimulus encodes a specific odor and is interpreted
by higher orders of the cerebral cortex. Population coding offers hundreds of
thousands of receptors to be able to discriminate odors, thus giving us a great
range for smell.
Olfactory Maps
The idea that specific neurons are linked to specific glomeruli in a
specific area of the olfactory bulb to interpret a specific odor. Thus, forming a
spatial pattern and contain specific maps or roads that odorants follow
depending on the stimuli nature.
Temporal Coding
The idea that a specific number of spikes or AP sent to olfactory system
and are a form of code for specific odorants. This idea is behind the quality and
concentration of the smell. Does a high conc and pure smell stimulate a specific
number of spikes than a lower quality? Does it code for a specific odor? Does
the timing of the spikes influence factors of the odor and how it is interpreted?
Research is continuing..
Vomeronasal Organ
The idea that pheromones are linked to specific behaviors, emotional
regulation, identifying individuals and sex drive.
The Vomeronasal organ located in the nasal cavity which projects to
the olfactory bulb and to the hypothalamus (hormonal regulation).
It is believed that the vomeronasal organ could be linked to many
social behaviors from pheromones :
o A baby identifying a mother as her mother
o Sexual drive between girl and guy, from sweating and smelling
sex driven pheromones
o Marking individuals territory and expressing dominance
Do pheromones increase sexual behavior in humans? No convicting
evidence as of yet, BUT THERE IS BIG DOLLARS TO WHOEVER
FIGURES IT OUT! $$$$$$$$

 Vomeronasal Organ Pheromones

Brain Rhythms
EEG Electro-encephalogram is a piece of equipment used to
analyse the rhythms of the brain

 Electrodes are evenly distributed over the head, most evident over the
ceberal cortex. These electrodes detect populations of neurons firing
and giving off certain frequencies and amplitudal waves.
EEG is used to analyse the rhythms of patients who suffer from:
o Sleep disorders
o Epilepsy
o Brain Disorders
The EEG Waves (BAT-D)
Beta (>14 Hz) Beta waves are the small high hertz waves that are
associated with high cortical activity such as physical work or mental
work. Alert and awake state.
Alpha(8-13 Hz) Alpha waves are a bit less frequenct than Beta
waves and have a greater amplitude. Associated with relexation and
prominent during eye closure.
Theta (4-7 Hz) Theta waves are associated with sleep states, REM
sleep, drowsiness or hypnotic states. Theta waves also unsually
become prominent when problem solving.
Delta (>4 Hz) Delta waves are the slowest waves and have high
amplitudal waves. They are associated with deep sleep and
drowsiness.

 All these waves are prominent and in homeostatis inside an

individuals brain. Each type of wave is regulated and occurs
consistently through out the day. When there is too much loss of or
gain of a certain type of wave then problems occur.
Rhythms
Within the cerebral cortex, there are specific rhythms occur. These are
synchronize rhythms that develop in two ways. The two ways arise
from either a population of neurons firing at the same time together, or
being led by a pacemaker (thalamus).

Collective Methods (The Jam Session) A Neuron within the brain

starts firing and starts recruiting other neurons to start firing in syc with itself.
This is known as the collective method of brain rhythms. They all jam out and
play together in harmony.

Pacemaker A pacemaker or a conductor sets the brain rhythm and

recruits populations of neurons to start firing to the set pace of the conductor or
pacemaker neurons. The thalamus is a well known pacemaker of cortical
neuronal cells.
This is how brain rhythms are manipulated and to allow us to divide
them into the caterogories of Beta (fastest), Alpha (second fastest)
Theta (slower) and Delta (slow and large)
Thalamus Pacemaker
The Thalamus contains a lot of the pacemaker neuronal cells that set
the AP rhythm. Cells inside the thalamus have their axons that spread
throughout the cerebral cortex to be able to intereact with other psrts
of the brain.
Regions of the brain depend on the thalamic rhythmic neurons to
receive information and spread the localization of that rhythm to other
populations of neurons within the brain.

Seizures and Epilepsy

Seizure
A seizure is termed when neurons display abnormal behaviours that involve
electrical discharge. Signs and symptoms of a seizure are dependent on where
the electrical discharge occurs.
Convulsion
A specific seizure type where the whole body starts to convulse or contract. It is
derived from motor neurons to cause involuntary subtle movments/contractions.
Epilepsy
The continuous and spontaneous seizures that occur within the brain. Epilespy
attacks can be classified as general (involving the whole cerebal cortex) or
partial (involving a certain part of the brain). Epilepsy attacks usually can occur
from 30 seconds up to
The Causes?
Disturbance in the membrane potential of the cells.
Neurotransmitter inbalance : Up regulated acetylcholinergic
neurons or down regulated GABAnergic neurons.
Decreased inhibition of cortical or thalamic neurons. This is why
inhibition is so important, without inhibitory neurons our brain would
not function in homoestasis.

Seizure The imbalance of inhibitory and excitatory neurons firing.

Convulsants Antagonists of GABA receptors (inhibitory)
Anticonvulsants Prolong the activity of GABA within the synaptic
cleft. Used to treat epilepsy.
Genetic Predisposition (Mutated Channel)
Epilepsy can be inherited by containing gene sequences that code for
a dysfunctional or mutated ion channel (usually Na+). For example
a lot of epileptic patients contain a Na+ channel that tend to:
o Stay open long
o Let more positive ions inside the cell
o And therefore hyperexcite the cell.
GABA inhibitory gene sequences may also be mutated. Intern, not
allow the necessary inhibitory regulation to make sure the neuronal
cells do not over excite.
Types of Seizures
Partial Seizures
Partial seizures involve the localization of a seizure within the brain. Partial
seizures can be broken down even further into two groups:
Simple Partial Seizure:
A simple partial sezure is the localization of a seizure within a specific
part of the brain. It is within one hemisphere and doesnt propagate to the other
hemisphere. Consciousness is not lost
Complex Partial Seizure:
Complex partial seizure is the localization of the sezure to one part of the
brain, but it can spread from one hemisphere to the next hemisphere. It usually
origninated from the temporal lobes.
Generalized Seizures
Generalized seizures involve both hemispheres of the brain, they usually
occur from a partial seizure that starts in one specific area of the brain and
spreads Tonic-clonic Generalized seizures are the common well known seizure
when a patient looses consciousness, has repeated convulsions.
Myoclonic (muscle)
o Tonic Continual held contractio

o Clonic Repeated relaxtion and contraction

Secondary Generalized Seizure : Occurs when the seizure starts in
one hemisphere and spreads to the other hemisphere.
Therefore, a tonic-clonic generalized seizure involves seizures in both
hemispheres and convulsions of the body. Sufferers are usually unconscious and
cant recall having the seizure. Coming out of seizure they are usually
uncomfortable and not aware of what has happened.
Generalized convulsive epileptic is a type of seizure that involves no
breaks in between the seizures. If left un-treated the sufferer may die from
respiratory failure. Clonic part of the seizure involves the respritatory
muscles contraction and disabling being able to breathe, thats why a lot of
people who suffer form epileptic seizures sometimes turn blue.

As you can see, the

ampitudal waves
classified as a
amplitudal
hemispheres.

Electroencephalogram of a sufferer of seizures.

seizure is the synchronise, long high
within the brain. This seizure would be
general seizure as the synchronous, high
waves are spread throughout both
General signs include the fluttering of eyes,
loss of consciousness,
tonic-clonic
convultions.

Frontal Lobe Seizures

Abnormal
disturbances in
behaviour
Parietal Lobe Seizures
Somatosensory target.
Types of sensation
symptoms over the
body
Occipital Lobe Seizures
Visual cortex, patients are known to see flashing lights.
Temporal Lobe seizures

Olfactory and gustatory symptoms, patients are known to hear and

smell things.
Motor Cortex Seizures
Localized conic and tonic contractions

Treatments
Surgeons are known to remove certain parts of the brain where
seizures are most prominent. Parts of the corpus collosum are a typical
area to remove so that the seizures dont spread.
Drugs that increase GABAergic activity known as anticonvulsants
Current Research is in electrode stimulators that can be inserted into
parts of the brain and can restore and monitor normal wave rhythmic
function of the brain. Known as The Pacemaker of the brain.
Identifying lesions within the brain using MEG, fMRI and PET scans
and removing lesion.
The Hypothalamus
Anterior/inferior to the Thalamus is located the Hypothalamus. It is
known as the highest form of endocrine control in the body.
The hypothalamus is responsible for the tight regulation of homeostasis
within the body.
Examples include: pH regulation, oxygen regulation, temperature
regulation, blood pressure and volume regulation, digestion and so on.
The hypothalamus regulates these changes due to change from
environmental stimuli. Such as jumping in a cold pool. The
Hypothalamus would react to the stimulus and secrete a
neurohormone that acts as a chemical messenger and is sent around
the body to draw blood away from the surface and keep the internal
organs at 37 degrees.
The hypothalamus
Connected inferior to the hypothalamus is the pituitary gland.

Pituitary gland is divided into two sections. The anterior lobe and the
posterior lobe.
We are mainly concerned with the periventricular layer of the
hypothalamus that is responsible for the synthesis and excrection of
neurohormones.

 The Hypothalamus is a major part of the limbic system which is

concerned with a lot of the emotional drivers (motivation), higher
cognitive functions (cognition) and vegetative functions.
BASICALLY IT IS WHAT SEPERATES US FROM ANIMALS
AND MAKES US HUMAN.
Overview of Hypothalamus
Location : Inferior to the thalamus, it is connected to the pituitary gland
via the pituitary stalk.
Differences: Thalamus is the big relay and edit centre of the brain,
hypothalamus is vital to the homeostasis of the body. Damage to the thalamus
may endure loss of some form of cognition, somaticsensory (eg: some lost
feeling in your arm) whilst damage to the hypothalamus will prove fatal.
Function: The Hypothalamus is the highest order of endocrine control
within the body, the pituitary gland is the mouthpiece of the hypothalamus in
that the hypothalamus communicates to the body through the pituitary gland.
Hypothalamus integrates and regulates the somatic and visceral
responses from external stimulus to meet the needs of the body.
Secretion of Hypothalamus and Pituitary Gland
The Posterior Pituitary
The hypothalamus contains Magnocellular Neurosecretory Cells that extend
their axons into the posterior pituitary gland. This lobe is more of a storage
unit rather than a excretitory gland. The Hypothalamus actually excretes the
two neurohormones that are stored in the posterior pituitary gland.
Oxytocin and Vasopressin (ADH)
Magnocellular neurosecretory cells are responsible for the synthesis
of the neurohormones Oxytocin and Vasopressin (ADH),
NOTE: Posterior Pituitary lobe does not excrete the neurohormones
the Hypothalamus does. The Posterior pituitary is simply a storage
unit of the Oxytocin and Vassopressin.

baby

Oxytocin: Is excreted during pregnancy to deliver stronger

contractions via the uterus to push out DAT BABY! It
also stimulates the mammary glands to synthesize and
secrete milk and develops the
maternal bonding between the
and mother.
Vasopressin (ADH)

Regulates blood
volume (water) and blood salt
levels.

Kidney Liver HT
On top of the kidneys are located the
Renal Medulla and Renal Cortex. The
Kidneys regulate blood composition and water
retention. When the body is lacking water Renin
hormone is released by the Renal Medulla
which activates Angiotensinogen from the
liver. Angiotensinogen forms Angiotensin II
which is a vasoconstrictor to intern increase
and maintain BP. Angiotensin II also
stimulates the Hypothalamus to excrete the
neurohormone Vasopressin (ADH) which
increases the water renention of the kidneys by
taking up more H2O and stimulates the subfornical
organ which intitiates the sensations of thirst
behavior.
Anterior Pituitary Gland

and drinking

.
Parvocelllular neurosecretory cells are located the periventricular
area of the hypothalamus. This time, the anterior pituitary lobe is
actually a gland in that it synthesizes and secretes a multitude of
hormones.
The hypothalamus secretes hypophysiotropic hormones that either
STOP or START the excretion of anterior pituitary cells.

 Hypophysiotropic hormones enter the portal circulation and bind to

the receptors of the targeted neurohormone.

Example of the periventricular hypothalamus and the anterior

pituitary is the release of Corticotropin releasing hormone (CRH)
from the hypothalamus and into the anterior pituitary where
Corticotropin Hormone (CTH) is released into circulation. CTH
targets the adrenal cortex of the kidneys which intern secretes
Cortisol.
Cortisol is important in dealing is utilized in mobilizing glucose
stores, being able to deal with stress and is important in immune
suppression. (Cortisone is a analogue of Cortisol, notice that Dr
Dwyer injected it into your inflamed scars to reduce the swelling, or
in other words suppressed that immune response )
Due to Cortisol being a steroid, that is it is lipothilic, it is able to cross
the Blood Brain Barrier and become a product/substrate that uses
negative feedback to suppress the excretion of CRH.
Hypothalamus and The Visceral Nervous System (ANS)
The ANS is divided up into two systems. The Sympathetic and
parasympathetic. They have distinct pathways and complement each other in
their functions.

 Ganglion or Ganglia are a bunch of neuronal cell bodies outside the

CNS. Pre-ganglionic means everything BEFORE the ganglion and
post-ganglionic is everything AFTER.
Sympathetic Nervous System
Increased heart rate, decreased digestion, increased respirartory,
glucose mobilization. (Fight or Flight)
Parasympathetic Nervous System
Decreased heart rate, increased digestion, decreased resiprartory rate
and glucose conservation. (Rest and Digest).

Sympathetic Neurotransmitters
Preganglionic axons in the CNS exit the spinal cord at the thoracic and
lumber regions. They then synapse onto the sympathetic chain which is where
all the ganglion are present.
Pre Ganglionic Acetylcholine
Post Ganglionic Norepinephrine

Parasympathetic Neurotransmitters
Preganglionic axons leave the CNS at the brain stem and at the sacral area of
the spine. Notice that their ganglion are much further away from the spinal
cord and more near the organs they effect. This is why their pre ganglionic
axons are much longer compared to the sympathetic pre ganglionic axons
Pre and Post The pre and post ganglionic neurons are all
acetylcholine baby!
The Enteric System
The enteric system is known the little brain within the ANS as it is
highly independent and can function without too much input from the ANS. It is
a complex and condensed network of neurons throughout the whole
gastrointestinal tract. It is composed of the two layer:
Myenteric layer
Submucous layer

Control of the Autonomic Nervous System

The periventricular area of the hypothalamus is connected to brain stem

nuclei and the spinal cord. The brain stem nuclei or part of the medulla known
the Solitary tract nuclei integrates a lot of the sensory information from the
internal organs and co-ordinates the output appropriately.
Solitary Tract Nucleus High order and integreation of ANS
Periventricular Releases neurhormones and regulates ANS (input
from the solitary tract nucleus).
This is why if a patient suffers severe head trauma around the cerebrum
they are enabled to sustain life if the spinal stem (where the medulla is located)
is still intact. Enabling to keep function of a lot of the visceral organs.
Diffuse Modulatory Systems
There are four diffuse modulatory systems within the CNS. They are
independent areas within the brain that release a unique NT. The four
diffuse modulatory release their neurotransmitter unique (Post
Synaptic) metabotropic G-proteins that allow prolonged and diverse
functions.
Norepinephrine located in the Locus Coeruleus
Involved with arousal levels and attention.
Seretongergic are located in the Nine Raphe Nuclei
Involved along with norepinephrine to form the ascending recticular
system
Involved with sleep/wake cycles
Dopaminergic are located within the Substantia Nigra and Ventral
Tegmental
Substantia Nigra, involves the voluntary movements in the muscles
(eg: damage to this area is related to Parkinsons Disease)
Ventral Tegmental is involded with psychiatric disorders and the
reward system.
Cholinergic are located within the Pontomesenchephalotegmental Complex
and medial and septal nuclei.
Pontomesenchelphalotegmental is involved with regulating the
excitatory of the thalamus nuclei

 Medial and Septal Nuclei is largely unknown but it participates in

learning and memory.
Drugs
LSD is a well known hallucinogen and contains a very similar structure
to Seretonin. Seretonin is related to a lot of our dreaming, so could it be
possible that the pronlonged effect of serotonin/LSD within the synaptic cleft
causes these hallucingoens?
Cocaine and Ampthetamine are stimulants and sympathomimetic drugs
that prolong the active dopamine and NE neurotransmitters within the synaptic
cleft. This is done by blocking the reuptake of the the neurotransmitters.

Mental Illness
Anxiety Disorders
Agoraphobia/Panic disorders
OCD
Biological evidence/treatment

Anxiety disorders are characterized by the inappropriate expression of

fear. A lot of anxiety disorders are due to a stressor that activates the stress
response within the person. Some examples are of anxiety disorders are:
Agoraphobia: Is a type of anxiety disorder involved when the person is
fearful if they cant escape a stressful situation, unable to have control of a
situation or feel they are being trapped within a stressful situation. Examples
include being claustrophobic, being a passenger within a car, on a boat and cant
see a possible escape route and being within a big crowd of people.
Panic Disorder: is involved with stimulating stressor that evokes a
unpredictable panic attack in which can include sympathetic stimulation, heart
palpitations, increased breathing
OCD: Also known as obsessive compulsive disorder is where a person
becomes anxious in a situation when a particular personal obsession is activated
or not in order. It involves the reoccurring thoughts of an obsession and exerts
certain behaviors. Examples include: germ freaks, specific patterns and orders
that if disturbed cause stress, counting and checking. A man with OCD is
known to check all the locks on doors and windows at least 20 times a night
before he goes to bed. Even then, he will wake up and re-check them.
Biological Basis of Anxiety Disorders
Stress Response
The Hypothalamic Pituitary Axis is involved in the stress response of
the body. High activity of this area causes the release of CRH that releases
ACTH into the blood stream that released cortisol from the renal medulla.
Cortisol a hormone to help deal with stress.
The Amygdala (responsible for a lot of emotions) is responsible for
activating the HPA.
The Hippocampus contains glucocorticoid receptors that bind Cortisol
and produce a negative feedback to lower the activity of the HPA from releasing
CRH.
Continuous exposure of Cortisol to the Hippocampus causes the neuronal
cells to wither and die. Therefore, decreasing the ability of the negative
feedback loop and causing a vicious rise in the stress response..sad

Amygdala and Hippocampus, HPA (Hypothalamic Pituitary Axis)

Treatments
Psychology (to adapt patient to fear)
Anxiolytic Drugs ( reduce anxiety via feedback loop)
o SSRIs Drugs that prolong the activity of serotonin within
the synapse eg: Fluoxetine and
o GABA agonists Drugs that bind to GABA receptors and
increase inhibition.
Affective Disorders
Major Depression
Bipolar
Biological evidence/Treatment
Major Depression
Major depression is clinically diagnosed when a patient has been
suffering from the severe prolonged symptoms of depression, these include
Feelings of worthlessness
Insomnia and also hypersomnia
Reduced appetite
Reduced concentration

 Thoughts of suicide
Prolonged exposure to all of these symptoms can therefore be evidence to
diagnose depression. Periods of genuine depression last for months onto years
and patients readily relapse into the condition. It is calculated 50% of patients
left untreated will relapse into major depression and 70% after 2-3 episodes will
relapse also.
Bipolar Disorder
Type I
Type II
Type one bi-polar is usually associated with symptoms of mania
(repetitive fluctuations of euphoria and overexcitement) whilst type two is
associated with as the name implies, the repetitive fluctuations between periods
of mania and periods of depression.

Major depression and Bipolar disorders have been linked to the in balance of
two of the main diffuse modulatory systems within the brain. The in balance of
serotonin levels and norepinephrine levels has been attributed to the diseases.
Two theories of Mood Disorders
Mono-Amine Hypothesis
Depletion or reduction of serotonin an norepinephrine within the
diffuse modulatory systems.
(MAO) degrading enzyme is too active.

 Depression is linked to the reduction of one of the systems (either

norepinephrine or serotonin or both)
Treatment Antidepressants
Fluoxetine blocks 5-HT reuptake transports, therefore prolonging the
exposure to serotonin.
Norepinephrine drugs that block the reuptake transports for
norepinephrine.
Blocking the activity of MAO

The Stress Response (Diathesis/Predisposition)

Diathesis: genetic predisposition
HPA (hypothalamic pituitary axis) is the site where genetic and
environmental influences merge to form hyperactivity therefore
mood disorders.
HPA releases CRH that causes ACTH from kidneys and trigger the
stress response.
The Amygdala HPA and Hippocampus as we have said are involved in the
activation and deactivation of the stress response.

In depression the negative feedback loop is damaged within the

hippocampus.
Treatment
Electric shock therapy
Is actually still used today. Induced seizures of the temporal regions
where the amygdala and hippocampus are located. Seems to be effective in the
short term but may cause memory loss.
Antidepressants Fluoxetine, Valium, Lithium
Psychology to help identify the stressors or stimulators within
patients disorder. Discuss issues and methods in ways to decrease the
Future treatment
A promising drug that will bind to hippocampus glucocorticoid
receptors and increase the negative feedback of CRH from the HPA.

Central Vision System

Retina Ganglia Lateral Geniculate Nucleus (LGN) Striate

Cortex
Rentiofugal Pathway

(Retino : Retina, fugal : fleeing from)

 The retinofugal pathway starts at the retina, synapses onto the LGN
and ends within the striate cortex (visual cortex) of the brain.
Each eye has a visual field in which cross over between the eyes at
the optic chiasm. From the optic chiasm they are segregated all the
way to the LGN and followed by the striate cortex.
Hemi-fields
hemisphere)

(Each eye projects into its opposite

Right Hemi-field and Left Hemi-field :

There is cross over between the two hemi-fields of each eye at the
optic chiasm.
After the optic chiasm the nerves are segregated and go into the
opposite hemisphere. Right eye goes to the left hemisphere and left
eye goes to the right hemisphere.

90% Optic Nerve LGN Striate Cortex

10%
Hypothalamus
Pretectum Pupil Dilation, certain eye movements
Superior colliculus Makes you respond to new stimulus, eg:
something in your peripheral.
Memory Systems and Learning I

(The Where)

Declarative Memory: (Hippocampus and Rhinal Cortex)

Being able to declare facts and events
Non-declarative Memory: (Striate cortex)
Procedural Memory : habits, skills, learned tasks. We remember these
learned tasks eg: riding a bike and their associated reflexes and
emotions.

Declarative memory is mostly associated with the medial temporal lobes.

Within this region the Hippocampus and Rhinal cortex are located, this is where
consolidation of declarative memories occurs. Declarative memory means you
are able to declare facts, statements or re call specific events. Whilst non
declarative memory is more associated with the Striatum and relates to the
learned procedures or habits of the individual in other words a procedural
memory. Examples include playing a guitar, your mouth watering when you
hear mum put the plates out for dinner or the memory you associated with a
snake, to intern run away to a safe haven. These are all examples of your nondeclarative memory which encompasses your procedural memory.
Amnesia: The loss of memories or inability to learn or form new ones.
Retrograde: Retrograde refers to the inability to remember before a
specific event. So, you forget things you already knew. For example a
man with severe retrograde amnesia derived from Parkinsons
disease is unable to recognize his children or wife.
Anterograde: Anterograde refers to the inability to form new
memories. An example of anterograde amnesia patients who suffer
from Parkinsons disease and cant moves houses because he will need
to learn the new layout and wouldnt be able to function.
Retrograde Memories before are forgotten
Anterograde Unable to form new memories
THE SEARCH FOR THE ENGRAM!
The biological understanding of where memories are processed and
stored.
These are known as Engrams.
The Theories

Lashleys Theory
Hebbs Theory
Macaque Monkeys
Electrical Stimulation of MTL (Medial Temporal Lobes)

1. Lashley Disproven

Lashley proposed that memories and learning were done all over the
brain and that all cortical areas contribute to memories and learning. His
experiments showed that the size of lesions contributed and therefore must
imply that memory and learning are widespread .
This theory was disproved as engrams show that memory and learning are
more localized to the changes specific structures of the brain. However Lashley
was right that memories are distributed into specific neuronal sections for
processing and storage.
2 . Hebbs Theory Current Theory
Hebbs proposed that the sensory systems, processed and held the engram.
Such as the visual cortex would interpret, process and store visual memories.
Eg: the recognition of faces (shape and color) would be found within the
ventral stream of vision (Area IT)
Cortical areas can be used for processing information and storage of
memories Hebbs Theory
A study was conducted onto two groups of people where one group of people
were experts in motor cars and one groups were experts in birds.
Due to these types of memories being sensory it was hypothesized that visual
processes and memories were done within the same place.
Bird enthusiasts only responded
very well to bird pictures and
being able to tell everything about
the bird, whilst car enthusiasts
only responded very well to car
pictures and could tell everything
about the car.

Conclusion: This hints towards

that the striate cortex is both used for
processing of sensory information and storage of memories. Therefore,
backing up Hebbs theory.

The Medial Temporal Lobes (Hippocampus and Rhinal Cortex)

Studies done on Humans and Macaques showed that within the
Inferotemporal Cortex a lot of recognition shapes and colors is
processed (The Ventral Stream in Dr Simmons Lecture).
Area IT or the inferotemporal area are involved in declarative
memories.
Medial Temporal lobes Declarative Memory
The Medial Temporal Lobes are made of the Hippocampus and the Rhinal
Cortex (MTL)
Through studies such as the Macaque Monkeys and Lobectomy of the
MTL show that lesions to these cause severe Anterograde Amnesia
and impaired Declarative memory. Suggesting that these areas
within the brain are important in storage of events and facts. Therefore
memory and learning deficits occur when areas to the MTL are
damaged
Study on Russell Crowe Medial Temporal Lobe (Fake)

Russell Crowe had an accident involving a sharp blow to the temporal

side of his head. Surgeons had to remove parts of his medial temporal lobe to
ensure his survival.
Russells personality, perception and cognition was mostly normal but it
was found he had severe anterograde amnesia and was unable to recall his
psychiatric after her spending 30 years studying him. If Russell was asked to
repeat a number or recall a phrase after a period of time he had totally forgotten
the number and the fact that the therapist had asked him to remember. This
suggested Russells declarative memory was severely damaged. Although
Russell could do most day to day things within his home, meaning his nondeclarative memory which encompassed his procedural memory was still
intact. Russell was able to form habits and skills (non-declarative) but couldnt
remember acquiring those skills (anterograde).
Conclusion:
The Medial temporal lobe is used for the consolidation of declarative
memories. If damaged you cannot retain facts and events and therefore suffer
severe Anterograde amnesia.

Sensory input is vital in the consolidation of memories. Input from our

senses enables us to process it down into the associated cortical areas. A lot of
consolidation of memories is found in the MTL (Hippocampus + Rhinal Cortex)
The Diencephalon and Memory Processing (Outside the MTL)
Dorsomedial Thalamus Nucleus
Anterior Thalamus Nucleus
Mammillary Bodies (Hypothalamus)
These areas are highly involved in recognition
Case: Radio technician had a pole that stabbed through his dorsomedial
thalamus in which memory impairment occurred. Suggesting that these
structures the dorsomedial thalamus nucleus, anterior thalamus nucleus and
mammillary bodies are connected to the MTL (Hippocampus+ Rhinal )
Korsakoffs Syndrome: Alcoholics are at high risk of brain damage due
to excessing drinking causing Thiamin levels to drop. The depletion of
Thiamin causes MTL damage and the onset of Amnesia (Retrograde and
Anterograde) along with declarative memory impairment.
The Hippocampus
The graph shows hyperactivity in the hippocampus when an old
memorable object is shown to the specimen.

 Hippocampus is vital in consolidation of memory. The hippocampus

is mostly involved in declarative memory although has diverse
functions such as:
o Working memory Digit span, 43963358
o Spatial memory Knowing where youre phone is at night
o Relational Memory Hippocampus can combine relations
within the context of one memory. For example relating the
smell of a food, the tasting of the food, where it is locate in your
pantry (spatial) and what it looks like (visual)

Radial Arm Maze

The radial arm maze that is used to test the spatial working memory
of rats. Working memory is short term processing memory (digit span)
that occurs to logically deduce that one arm does not contain food and
to remember it doesnt contain food. Therefore the rat can eliminate it
from the equation and move to the next arm.

 Lesion in the Hippocampus impairs working memory and the rat

will continuously go back and forth into the arms it has already
checked. Therefore, the hippocampus serves a function of working
memory.

Water Platform Spatial Memory Place Cells

The rats are placed within a water bowl where they swim around to
find a hidden platform. After they have learned where the platform is
which is Spatial Memory they able to go straight there.
Lesion in the Hippocampus can lead to impairment of Spatial Memory
where the rats swim around continuously and cant remember spatially where
it is.
Place field cells relate to cells within the hippocampus that fire when
spatial memory is induced.
Spatial Memory NMDA Glutamate (Lecture 2 for MS and L)

Striatum and Procedural Memory (Non-Declarative)

Random Exam Q: Basal Ganglia are vitally important in emotion.

The Striatum is vital in Non Declarative Memories in that it is vital
in habits and procedures.
The Substantia Nigra (Dopamine) is connected with the Striatum
which would make sense because its related to the co-ordination of
movements which would come from the procedural memories.
Lesions in rats within the Striatum show that they lose procedural
memories or habits that have been identified.
All these structures are part of the Basal Ganglia!!
EXAM: Basal Ganglia are vitally important in EMOTION
An example would be input from Sensory Cortex to inform the person of
the stimulus, through to the Striatum where the procedure to rectify the
stimulus would be remembered and off to Motor-Cortex to initiate the
movement that has come from remembered procedure or habit
Eg: A cricketer having a ball thrown at them
Visual Sensory Striatum (remembering associate habit) Thalamus
Motor cortex Executed Movement

Summed up
Damaged Hippocampus Degraded perform on maze task and impairment of
declarative memories
Damaged Striatum Degraded on a modified maze task and impairment
of non-declarative memories (habits and procedures).
Modified maze task can include associating a light with food, or without food.
The rats usually use their working + declarative memory to know where the
food is located within the maze. If they have learned procedural/habits to find
the food, then they can find it faster. Damaged to the striatum and modifying
the maze will lead to rats degradation of non-declarative memory and hence
procedural memory (habits/skills/tasks) are impaired.
Case Study
Parkinsons Disease Patients
Amnesiac Patients
`

Substantia Nigra (dopamine) is associated with the Striatum in forming

non-declarative memories where our procedural memory and habits are
formed and used. A study was done between Parkinson Patients (Striatum
impairment) and Amnesiacs (Hippocampus impairment).
Parkinsons Patients scored poorly on association tasks involving putting
together the correct symbols to tell what the weather was doing eg: squares and
triangles represent sunshine.
Contrary to that was the amnesiacs scored quite well in comparison to
the Parkinsons patients. But when faced with a questionnaire on facts they
scored poorly.

Conclusion: Parkinsons patients and amnesiacs have damage to

different parts of the brain, implying that declarative memories are stored in
the MTL (Hippocampus and Rhinal Cortex) and Parkinsons patients have
impairment of non-declarative memories found mostly in the Striatum.
Working Memory and the Neocortex
Prefrontal
Prefrontal
problem

Cortex is shown within our primates.

cortex is heavily involved with working memory,
solving, consciousness and planning.

When memories are derived from storage

(MTL) they come to the prefrontal cortex
where we are conscious about them.
From there we can begin to start and
solve a problem (remembering a
equation?) and become conscious of the
memory. Our pre-frontal cortex is where
stimulus enters the working memory
(digit span) where they can be held for a
while until the brain (depending on the emotional context, repetition,
environment) either uses the information and chucks it away (Anterograde
amnesia) or consolidates the information which goes through the procedures to
short term and long term memory.

Diagram showing flow from MTL structures to the pre frontal cortex.

Wisconsins Card Sorting Experiment.

Working memory is vital in the cortex. Patients were asked to first sort
the cards via their colour (non-declarative). Once they were sorted they were
then asked to rearrange via shape. This required the working memory as
patients seem to lose tract of making mistakes and tend take a lot longer due to
impairment of the pre-frontal cortex where the working memory is located.

COOL STUFF!! Now lets dive into the physiology of memory

Memory Systems II
Memory Systems and Learning II
Memory/Learning Occurs by synaptic modification!!!!
Procedural Learning (Non-Declarative Memory)
Non-Associative Learning (Habituation and Sensitization)
Associative Learning (Classical and Instrumental conditioning)

Non- Associative Learning 1 Stimulus

Habituation
Sensitization
Habituation in our procedural memory (non-declarative Striatum) is
the de-sensitization to a stimulus. As the stimulus occurs repetitively we adapt
by forming a habit to not respond to that stimulus.

(MCQ)

Sensitization is the increased response to a particular stimulus. For

example walking down an ally way and suddenly there is no light. You are
sensitized to this type of stimulus. Therefore, increased response.
(MCQ)

Associative Learning Two Stimuli !

Classical Conditioning
Instrumental Conditioning
Classical Conditioning

Involves the pairing of a unconditional stimulus with a conditional

stimulus to form a conditioned response.

In this example the un-conditional stimulus is the food. In which the

food forms a response (salivating) that doesnt require any conditions. When we
combine a conditional response such as a ringing of the bell the dog doesnt
respond as it doesnt associate the bell with the food.
After training the dog and ringing the bell before every time you feed the
dog, you are conditioning the response. In that the conditional response has
now been associated with food. The condition being that every time you ring
that bell food will be associated and you will have a conditioned response.
Classical Conditioning UCS + CS C R

Instrumental Conditioning
Instrumental conditioning is involved with a behavior which is
associated with a response. For example, a rat that is placed within a box will
eventually bump a lever which releases food. The rat learns through
instrumental conditioning that the behavior of pushing the lever will evoke the
response of the food.
Behavior Associated Response

Another example of instrumental behavior is in playing the guitar. It is

noted that when the association of playing the guitar (behavior) you get a
pleasant response from the crowed (response). (the guitar must is obliged to be
good, other it will evoke a bad response)

Learning in Aplysia
Studying Advantages of Aplysia
Non-Associative Mechanism (habituation/sensitization)
Associative Mechanism (Classical Conditioning/Instrumental C)
Studying Advantages of Aplysia
Studies can be taken out on Aplysia which are invertebrates.
Invertebrates such Aplysia are easy to study on due to many advantages their
nervous system which include:

Simple Nervous System

Large identifiable Neurons
Small Genome
Identifiable circuits and branching

Aplysia have a relatively small nervous system, large identifiable neurons

which make it much easier in the lab to study due to microscopy not being
needed. Their small genetics allows specific structures to be easily identifiable,
isolated and studies further. Overall, Aplysia are a dubbed down, much more
simple nervous system in comparison to the human nervous system. These
distinct advantages allow the studying of a higher complex organisms easier as
there can be similarities drawn out.
Non-Associative Learning Aplysia
In non-associative learning we are looking at the habituation and
sensitization of Aplysia.
Habituation is tested by spraying water around the gills of the Aplysia.
Initially the slug reacts very strongly and retracts it gills. Repetitive sprays and
the slug habituates to the stimulus. This is due to

Habituation: Pre-Synaptic modification by DECREASING Ca++

intake
As the slug adapts and realizes its not a threat, the presynaptic ends of
neurons intake less calcium and therefore little NT (glutamate) is released to the
motor neurons to reduce the response.
Sensitization is tested via poking the slug in a different area such as the
tail at the same time as the water jet.
5-HT (Serotonin) is released from L29 that makes increased
glutamate release from the sensory
neuron to the motor neuron. 5HT release creates a 2nd
Messenger to create cAMP
from

Adenylyl cyclase activation.

Phosphorylation occurs.

to increase
Synaptic
Cerebellum
The

GLUTAMATE release is related

Sensitization
Plasticity of the
Purkinje cell is the core of

motor learning.
Parallel fibers and climbing fibers are the pre-synaptic terminals whilst the
Purkinje cell ins the post synaptic terminal.

Long Term Depression (LTD) is the decrease in EPSP. It can be

broken down into the learning phase and memory phase.
LTD is believed to be the core of Motor Learning
1. Parallel and Climbing fibers depolarize the cell simultaneously, (input
specificity).

2.
Climbing fibers
create increased [Na+] and
[Ca++] internally in
the purkinje cell. This
is the core of learning.
3. Parallel fibers release
glutamate which binds to AMPA
receptors and creates the usual 2nd
Messenger cascade.
4. Phosphorylation of
proteins is thought to be the
major step in how synaptic
modification occurs.
5. AMPA receptors are internalized and decrease the EPSP of
glutamate. This where memory is formed.
Learning [Na+]i and [Ca++]i levels intracellular and the
activation of Protein Kinase C (PKC)
Memory

Internalization of AMPA receptors.

Input specificity of both fibers in learning and memory. Internalized

AMPA and increase in Na and Ca.

 Comparison between invertebrate and vertebrate.

If we can consider LTD results in motor learning of the Cerebellum then
Learning and memory result from synaptic modification
Synaptic modification occurs through 2nd Messenger and
phosphorylation (Protein Kinase C)
Memories occur from the alteration of the existing synapse.
Synaptic Plasticity of the Hippocampus
As we known the Medial Temporal lobes are vital in our declarative
memory. Particularly the hippocampus. Within our hippocampus
these declarative memories are thought to be formed by both Long
Term Depression (LTD) and Long Term Potentiation (LTP)

LTD and LTP are the basis of learning and forming declarative memories
in the Hippocampus

Concerned with CA1 and CA3 areas of

the Hippocampus/Rhinal

Just like we saw in the cerebellum with the parallel fibers and
climbing fibers, it was input specific by the simultaneous cooperation of the two.
We need input specificity by high frequency EPSP to the CA1 cell
within the hippocampus. This will give a strong response or a Long
Term Potentiation (LTP).
LTP can last for days, months, years or even a life time! No wonder
we can remember specific events from our early childhood. As they
created enough high frequency input to form a LTP.

So how does this work?

We saw within the cerebellum that AMPA receptors were vital in
responding to glutamate from the inputs from the parallel and
climbing fibers stimulus to form a LTD. In the case of CA neurons
within the Hippocampus, we need BOTH NMDA and AMPA
receptors to either form a LTD or LTP which are both vital in
declarative memory and learning.

CA1 and CA3 have both AMPA and

NDMA glutamate receptors.

the

1. Ca++ influx to presynaptic terminal

causes glutamate to be released.
Depending on how much Ca++ influx
occurs will depend how glutamate will be
released.
2. Glutamate binds to both
its post-synaptic receptors AMPA and
NMDA. Na+ comes into the cell.
3. NMDA is voltage gated dependent, thus the cell needs to reach
depolarization to remove Mg++ block.
4. Mg++ block will remove and Ca++ will rush through
NMDA receptor into the post-synaptic
cell.
5. Depending on how much Ca++ is
pushed through will depend on if a
LTP will occur.
6. High amounts of Ca++
entering the post-synaptic will depict
how much Ca++ was influxed into the
presynaptic terminal. LTP will occur
when Ca++ binds to PKC and
CAMKII.

CA1 and CA3

The phosphorylating of AMPA receptors. Adding and subtracting
AMPA receptors that strengthen signals between neurons. Neuronal
plasticity is bound by this idea. LTPs and LDPs are the basis of
learning and memories.

to AMPA

Glutamate is released at the CA 3 cell and binds

and NMDA receptors.
NMDA Mg++ is released on
depolarization and activates Protein
Kinase C.
Long term Potentiation is created by the
insertion of AMPA receptors to the
membrane or changing the effectiveness of
AMPA receptors.

Therefore strengthened
pathway! Stronger pathway, more
AMPA
receptors. The linking of neurons. Its creating
fucking declarative facts! And its fucking
awesome! This is your fucking brain at the
molecular fucking level making sure you
fucking remember that fucking
quadratic equation formula in your maths exam. Like umm? Omg wow tehe

Both LTP and LDP can occur through NMDA Receptors (BCM theory)

 The measure of activation of NDMA is dependent on whether a LTP

or LTD will form.
Dont forget, that the Mg++ has to be removed for Ca++ to pass
through. If you dont have enough stimulation of NMDA than LTD
will most likely occur. High levels of NDMA activation (in other
words stimulating your brain) will remove the Mg++ block and allow
Ca++ to flow through to form LTP. Adding of ADMA or making it
more active! Dephosphorylating AMPA will induce LTD. (less
calcium).

Both LTP and LDP can be made, dependent on the influx of Ca++.

 Low influx of calcium to the post-synaptic membrane (NMDA) will

result in the de-phosphorylation of AMPA receptors within the
membrane. (protein phosphatase)
High influx of calcium will result in the phosphorylation of AMPA
receptors. (Protein kinase)
Overall
Studies have shown that the basis of learning and memory is situated
around the modification of the synapse. Within the Hippocampus
the phosphorylation of AMPA receptors is regulated by LTP and
LTD.
AMPA receptors within the post synaptic cleft are being regulated
continuously.
LTP and LTD are dependent on the concentrations of Ca++ that run
through the NMDA G coupled protein.
Long term potentiations and Long term depressions are the basis
of how much AMPA is added removed or modified at the post
synaptic membrane.
Protein PSD-95 is a major protein that regulates the capacity of how
much AMPA the post-synaptic terminal can hold.
Increased PSD-95 transcription of PSD-95 will increase the capacity
of AMPA receptors on the PS membrane.
Molecular Basis of Long-Term Memory
1. CaMK11
Long term memory is associated with continual phosphorylation of
AMPA receptors.
CamK11 is a protein kinase that has two conformations, the closed
conformation and open. Ca++/Calmodulin switches CamK11 to its open
position permanently due to the high levels of Ca++, thus it can continually
phosphorylate membrane proteins such as AMPA.
2. Protein Synthesis
Memory is developed through the synaptic modification via adding proteins.
Protein synthesis is conducted in the consolidation of memories.
Modification of the membrane proteins via protein kinases ensures they
modified but NOT ERASED. The synthesis of new proteins that are added
to the membrane plays a role in forming long-term memories.
3. CREB

CREB is a transcriptional factor that binds to cAMP response elements

along DNA to specific genes. These proteins are believed to make proteins
that are used in synthesizing new synapses between neurons to intern
create more connections and allow learning and memory consolidation. An
experiment with rats showed CREB transcription and 25% increase in
synapse connections.
Attention
Schizophrenia
Schizophrenia Schizophrenia is defined as the cut off from reality
and a disruption of mood, thoughts and perception. (Clinically Insane)
It was characterized from a doctor by Divided Mind. As the person
can oscillate from normal and abnormal states. Although there are many
manifestations of Schizophrenia. Most of them are degenerative.
4 types of Schizophrenia
Paranoid Schizophrenia
Disorganized Schizophrenia
Catatonic Schizophrenia
Un-differentiated type
Paranoid Schizophrenia : think people are out to get them,
hallucinations and hear voices. Always paranoid someone is trying to hurt them.
Remarkably these are the patients most likely to recover from treatment.
Disorganized Schizophrenia: flat effect. These patients appear
emotionless, with a blank face expression. They have disorganized speech and
behavior. These are the laughing/giggly type when talking. They are not
coherent and say things that make no sense.
Catatonic Schizophrenia: These include patients who have obscure
voluntary movements. Bizarre postures and peculiarity (slightly unusual)
movements. Motionless to bizarre hyperactive movements.
Undifferentiated Schizophrenia: This is where the schizophrenia cannot
be differentiated.

Symptoms
Positive Symptoms (extravert) : Abnormal thoughts and Behaviors
Delusions
Hallucinations
Disorganized speech (you have no idea what they are talking about)
Very disorganized and very catatonic (abnormal movements)
Negative Symptoms (introvert): Emotionless and non-responsive
Reduced
Non to little speech
Difficulty in initiating a behavioral goal (shaking someones hand)
Memory Impairment.
Schizophrenic patients have enlarged ventricles. A
MRI and CT scan usually shows the reoccurring patterns
of these enlarged ventricles within schizophrenic
patients.
This scan shows identical twins. One with
schizophrenia and the other without. If twins share 100%
identical genes and there is only a 50% chance of one
having schizophrenia where is the other 50%?
Environmental factors must been taken into account
then to set off schizophrenia. These are usually around
pregnancy and development.
Malnutrition
Drug abuse of mother (amphetamine)
Viral infections

Other areas are affected apart from enlarged ventricles. Schizophrenic

patients display physiological abnormalities such as:
Smaller prefrontal lobes (working memory? Consciousness?
Problem solving? Planning? Makes sense to go crazy.)
Reduction and disorganized pyramidal neurons in cortical areas.
Thinner cortex layer in the Medial temporal lobes (memory
affected?, speech affected?)

Biological Reasoning
Genes and Environment : Inherited through family/malnutrition
Dopamine Hypothesis : Amphetamine and increased Dopamine
Glutamate Hypothesis : PCP and blocking Glutamate NMDA
1. Genes and Environment
Genes: Schizophrenia can be a inherited mental disease in that the
more genes you share with a family line of schizophrenics will
increase your probability of acquiring the debilitating disease.
Environment: schizophrenia can be brought on by environmental
influences such as
o Poor nutrition during maternal care (drug abuse, nutrional
deficits)
o Stress within the environment
o Viral infections during fetal and infant development.
Biochemical Hypothesis : Dopamine and Glutamate
Dopamine Hypothesis : Excessive Dopamine
Amphetamine when used increases the Dopamine levels within the
brain causing euphoria and activating the reward system of
dopamine. As addiction persists, high doses are implemented to fulfill
craving. Overdose on Amphetamine closely relates to
Schizophrenia patients.
Excessive Dopamine levels within the brain are attributed to
Schizophrenia. Psychotic states occur when levels of Dopamine
suddenly rise.
o Too many D2 (Dopamine) receptors are found, thus too much
dopamine excreted.
o Treatment involves blocking D2 receptors using neuroleptics to
lower the levels of Dopamine activity.
Glutamate Hypothesis: Reduced NMDA Glutamate receptor
PCP was previously used as a anesthetic drug but was stopped as
patients post-operative were having hallucinations and hearing voices.
Today PCP is unfortunately a illicit drug used for recreational use
Angel dust or Hog.
PCP blocks NDMA channels and causes very similar symptoms of
Schizophrenia in drug users.

 Schizophrenia includes reduced NDMA receptors within the brain.

Thus reduced cortical Glutamate within the brain.

Treatments
Conventional Neuroleptics - Chlorpromazine and Haloperidol act on
D2 within the brain to reduce the amount of Dopamine.
Heavy side effects as the Substantia Nigra affiliated for Dopamine is
down regulated a lot and exhibits Parkinsons Disease
Muscle Rigidity, impaired non-declarative memories, tremors and
difficulty in coordinating movements.
Research: Studies are in increasing the NDMA expression within the brain
together with reducing D2 receptors within the brain.

Spinal Control of Movement

Striated Muscle: Encompasses skeletal muscle and cardiac muscle.
Smooth muscle: involves gastrointestinal tract, arteries and veins.
( Innervated by ANS)

We are now looking at the Peripheral Nervous System (PNS). Where we

have voluntary control.

The dorsal horn receives sensory

information.

at

Now we are
looking
the

ventral
horn
where motor neurons
are
to travel along the ventral root to
innervate peripheral muscles.
Lower motor neurons are found
within the spinal cord. These are the neurons
receive the message from the higher neurons
brain. Contraction is exclusively taken out by
lower motor neurons.

held

which
in the

Uneven muscle distribution throughout the body eg: a lot more

individual muscles in the arms and legs. Thus enlarged areas of the
cervical (arms) area and lumber areas (legs) where a lot of spinal
nerves leave the body.
Lower Motor neurons Ventral Horn
Inside the ventral horn is where motor neurons are. Although there are
specialized motor neurons that carry out particular tasks.
Flexor motor neurons lie dorsal to the extensor muscle neurons.
Axial motor neurons that control posture are medial to the distal
muscles.

MCQ

MCQ
Alpha
neurons
innervate
muscles
are the
neurons
allow contraction
occur.

and

motor
fibers
who
to

Motor unit: Includes the single alpha

motor neuron that innervates the muscle fibers.
Motor Neuron Pool: all the alpha
that innervate a muscle.
Refer to the diagram.

neurons

Graded control the frequency of depolarizations directly effects

whether a muscle will twitch or fully contract. Temporal summation of causes
twitching of the muscle. When we reach high frequencies we see full
contraction of the muscle.
Inputs to Alpha Motor Neurons
Dorsal root sensory information (muscle spindles)(proprioception)
Interneurons ( Inhibitory and Excitatory)
Upper motor neurons (send signals to produce movement)
Muscle Spindles MCQ
You have alpha motor neurons that innervate the muscle to contract.
Inside muscles are muscle spindles that are vitally important in proprioception
and reflexes that encompass interneurons.
Gamma motor neurons innervate muscle spindles directly so that the
muscle-spindles can shorten and lengthen in movement of the muscle

Intrafusal Muscle is innervated by Gamma Motor neurons. This is

where the muscle spindles lie. Connected to muscle spindle is also 1a sensory
neurons that work with the gamma motor neurons and alpha motor neurons
in communication.

Extrafusal muscle contain our Alpha Motor

Neurons used to contract and relax the muscle.
Intrafusal Gamma Motor
Neurons
Extrafusal Alpha Motor
neurons
MCQ
1a Sensory Neurons send
information such as position in space,
length, load of contraction and so on so that
the Alpha Motor Neurons can act
accordingly.

Muscle spindle with gamma motor neuron and 1a sensory neurons.

When the muscle contracts from alpha motor neuron the muscle spindle
slackens and goes off air. 1a sensory neurons send signals off to spinal cord
and tell gamma motor neurons to contract the muscle spindle so that it is the
same length of the extrafusal muscle fibers. Now the muscle spindle is back on
air and 1a sensory receptors are firing again. Thus, the muscle spindle is
innervated by special nerves including gamma motor neurons and 1a sensory
neurons to act independently from the extrafusal muscle and alpha motor
neurons. In turn allowing us to have proprioception
Gamma Motor neurons Keep muscle spindles on air

Monosynaptic/Myotatic Reflex Arc

1. Muscle elongates due to force

2. 1a Sensory neurons fire
3. Alpha Motor neurons respond and fire
4. Contraction.

Golgi Tendon Organs send information about muscle tension. In other words,
make sure you dont rip your muscle off the bone. These Golgi tendon organs
are located in the two poles of the muscle tendon and have 1b Sensory Neurons
innervating them.
1b Sensory Neurons innervate Golgi tendon organs. Another form of
proprioception and part of the reflex arc if the muscle is under too much
tension. Although can be overridden by higher cortical areas.

Overview of Neurons
Alpha Motor Neurons Extrafusal Muscle Fibers
Gamma Motor Neurons Intrafusal Muscle Fibers (Muscle Spindles)
1a Sensory Neurons
Innervate extra and intra muscle fibers
1b Sensory Neurons
Golgi Tendon Organ
Proprioception at Joints
The combination and workings of muscle spindles, Golgi tendon organs and
skin receptors.
Interneurons Excitatory and Inhibitory
Inhibitory Effect

Interneurons a crucial role in reflexes and movement. In this example an

interneuron can be inhibitory when you contract your bicep, the interneuron
inhibits the alpha motor neuron for the tricep, thus allowing it to relax and
lengthen so you may contract your bicep.
Excitatory Effect Flexor Reflex
Interneurons in this example are involved in a reflex arc. These interneurons are
playing a crucial role in exciting the flexor muscles to contract and withdraw
from the painful stimulus.
1a Sensory neuron depolarizes as you step on thumbtack. Action potential
reaches the interneuron. Interneuron passes signal to alpha motor neuron to
contract hamstring to release foot from painful stimulus.

Cross Extensor Reflex

Cross extensor reflex is the inhibitory and
interneurons. When you step on the thumbtack

Start
questions
Brain Control of Movement

excitatory actions of
the interneurons excite
alpha motor neurons for
flexors to contract and
remove from painful
stimulus. At the same time,
interneurons cross over to
other side of the body to
inhibit the flexor action on
the other leg. Instead the
extensors are stimulated to
take load while the other
leg is being removed.
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