Functional Neuroanatomy
• Sensory System – process external stimuli
• Association Units – integrates sensory input with
internal drivers and emotional stimuli
• Motor System – manipulates external environment
Intermediate brain (paleopallium)
• Limbic system
o Emotions
Primitive brain (archioallium)
• Self preservation, aggression
Rational brain neocortex (neopallium)
• Intellectual tasks
Sensory Systems
• Somatosensory
(light touch, pressure, pain, temperature, vibration,
proprioception)
• Visual (see)
• Auditory (hear)
• Olfactory (smell)
• Gustatory (taste)
Two Paradigms on the formation of the final synaptic
arrangement
1. Genetics and Experience / Nature and Nurture
– Fiber projection arrangment organized by
fixed and diffusible chemical cues
– modeling and remodeling on the basis of
coordinated neural activity (activity-
dependent formation of synaptic
connectivity)
2. Presence of highly specialized brain cells that respond
exclusively to extremely specific stimuli (cellular
localization of specific feature extraction) e.g.
“grandmother cell”
Somatotropic organization of the Somatosensory System
(Refer to figure on the ppt)
Fiber sorting after entry to spinal cord
1. Synapse within one or two spinal segments
2. Conscious perception of touch, temperature, pain, decussate
on entry and ascend throughspinothalamic tract
• Lateral spinothalamic: localized, discrete, acute
pain
• Medial spinothalamic and spinoreticulothalamic :
diffuse, chronic pain
3. Conscious perception of touch, proprioception, vibration
ascend without immediate decussation through the
posterior columns
• All somatosensory fibers project to, and synapse in, the
thalamus
• The thalamic neurons preserve the somatotropic
representation by projecting fibers to the
somatosensory cortex
Somatotropic map (figure - refer to ppt)
Psychiatric implications
• Reciprocal connections in the somatosensory system
specifically fibers that project from and to the thalamus
and cortex serve to filter sensory input but in
pathological states may underlie psychosomatic
syndromes as conversion disorders.
Visual System
Central Visual Pathway
• Once the ganglion cell axons leave the retina, they
travel through the optic nerve to the optic chiasm, a
partial crossing of the axons.
• At the optic chiasm the left and right visual worlds are
separated.
• After the chiasm, the fibers are called the optic tract.
• The optic tract wraps around the cerebral peduncles of
the midbrain to get to the lateral geniculate nucleus
(LGN).
• The LGN is really a part of the thalamus, and remember
that nothing gets up to cortex without synapsing in
thalamus first
• Almost all of the optic tract axons, therefore, synapse in
the LGN.
• The remaining few branch off to synapse in nuclei of
the midbrain: the superior colliculi and the pretectal
area.
• The neurons in the LGN send their axons directly to V1
(primary visual cortex, striate cortex, area 17) via the
optic radiations.
• This highway of visual information courses through the
white matter of the temporal and parietal lobes, and
can be very vulnerable to strokes.
• Once the axons reach V1, they terminate primarily in a
single sub-layer of cortex.
• As the signal is transmitted to upper layers of cortex,
the information from the two eyes is mixed and
binocular vision is created
• but in yet another layer the two eyes are still entirely
separate. Therefore, if you could label the inputs from a
single eye, you would see little pillars of label which line
up next to each other and form tiger stripes. These are
the ocular dominance stripes. (stereoscopic
localization)
• Primary visual cortex: lines of specific orientation
• Secondary visual cortex: particular movements and
angles
• Inferior temporal Cortex (ITC): shape, form, and color
• Posterior parietal Cortex: location, motion, and distance
• Left ITC: facial features
• Right ITC: complex shapes
Disorders of Visual Perception
• Prosopagnosia (inability to recognize faces)
• Apperceptive Visual Agnosia
– (inability to identify and draw from visual
cues)
• Associative Visual Agnosia
PLM Med Yr 2, Section C, Class 2012
Page 1 of 9
 – (inability to name or use objects despite
ability to use them)
• Color agnosia (inability to recognize color)
• Color anomia (inability to name color)
• Central achromatopsia
– (complete inability to perceive color)
• Anton’s syndrome (inability to acknowledge blindness)
• Balint’s syndrome
– (optic ataixa, oculomotor apraxia,
simultagnosia)
• Gertmann’s syndrome
– (agraphia, aclaculia, right-left disorientation,
finger agnosia)
Auditory System
Auditory Pathway
• The auditory nerve carries the signal into the brainstem
and synapses in the cochlear nucleus.
• From the cochlear nucleus, auditory information is split
into at least two streams
• Auditory nerve fibers going to the ventral cochlear
nucleus synapse on their target cells with preservation
of the timing of the signal to the microsecond.
• The ventral cochlear nucleus cells then project to a
collection of nuclei in the medulla called the superior
olive.
• In the superior olive, the minute differences in the
timing and loudness of the sound in each ear are
compared, and from this you can determine the
direction the sound came from.
• The superior olive then projects up to the inferior
colliculus via a fiber tract called the lateral lemniscus.
• The second stream of information starts in the dorsal
cochlear nucleus.
• Unlike the exquisitely time-sensitive localization
pathway, this stream analyzes the quality of sound.
• The dorsal cochlear nucleus, with fairly complex
circuitry, picks apart the tiny frequency differences
which make "bet" sound different from "bat" and
"debt".
• This pathway projects directly to the inferior colliculus,
also via the lateral lemniscus
Summary of the Auditory Pathway
• Fibers from the cochlear nuclei and the superior olive
(not the inferior) travel up the lateral lemniscus (not
the medial) to the inferior colliculus (not the superior),
and then to the medial geniculate (not the lateral) in
the thalamus which projects to primary auditory
cortex, located on the banks of the temporal lobes.
• Try remembering the mnemonic, "S-L-I-M" .
Olfactory System
• The axons from all the thousands of cells expressing the
same odor receptor converge in the olfactory bulb.
Mitral cells in the olfactory bulb send the information
about the individual features to other parts of the
olfactory system in the brain, which puts together the
features into a representation of the odor.
• Since most odor molecules have many individual
features, the combination of features gives the
olfactory system a broad range of odors that it can
detect.
• Odor information is easily stored in long term memory
and has strong connections to emotional memory.
• This is possibly due to the olfactory system's close
anatomical ties to the limbic system and hippocarmpus,
areas of the brain that have long been known to be
involved in emotion and place memory, respectively.
Olfactory Tract and Central Pathways
• Mitral cell axons project to the olfactory cortex via the
olfactory tract.
• Medial fibers of the tract contact the anterior olfactory
nucleus and the septal area.
• Some fibers project to the contralateral olfactory bulb
via the anterior commissure.
• Lateral fibers contact third-order neurons in the
primary olfactory cortex (prepyriform and entorhinal
areas) directly.
• Third-order neurons send projections to the
dorsomedial nucleus of the thalamus, the basal
forebrain, and the limbic system.
• The thalamic connections are thought to serve as a
conscious mechanism for odor perception, while the
amygdala and the entorhinal area are limbic system
components and may be involved in the affective
components of olfaction.
• Investigations of regional cerebral blood flow have
demonstrated a significant increase in the amygdaloid
nucleus with the introduction of a highly aversive
odorant stimulus, and this has been associated with
subjective perceived aversiveness.
Olfactory System
• Olfaction is tightly associated with sexual and
reproductive responses.
• The structures of higher olfactory processing in
phylogenetically more primitive animals have evolved
in humans into the limbic system, the center of the
emotional brain and the gate through which experience
is admitted into memory according to emotional
significance.
Gustatory
• Discriminate only broad classes of stimuli
• Detection and discrimination of foods involve a
combination of other senses
Autonomic Sensory System
Unconscious monitoring of basic functions necessary for life:
visceral organ activity, blood pressure, cardiac output, blood
glucose levels, body temperature
Motor Systems
• Basal Ganglia
• Cerebellum
• Motor Cortex
Basal Ganglia and Cerebellum
PLM Med Yr 2, Section C, Class 2012
Page 2 of 9

• The basal ganglia and cerebellum are large collections
of nuclei that modify movement on a minute-to-minute
basis.
• Motor cortex sends information to both, and both
structures send information right back to cortex via the
thalamus.
• The output of the cerebellum is excitatory, while the
basal ganglia are inhibitory.
• The balance between these two systems allows for
smooth, coordinated movement, and a disturbance in
either system will show up as movement disorders.
• a collection of nuclei deep to the white matter of
cerebral cortex.
• The name includes: caudate, putamen, nucleus
accumbens, globus pallidus, substantia nigra,
subthalamic nucleus, and historically the claustrum
and the amygdala.
Basal Ganglia functions and connections
• he caudate and putamen receive most of the input
from cerebral cortex; in this sense they are the
doorway into the basal ganglia.
• There are some regional differences: for example,
medial caudate and nucleus accumbens receive their
input from frontal cortex and limbic areas, and are
implicated more in thinking and schizophrenia than in
moving and motion disorders.
• The caudate and putamen are reciprocally
interconnected with the substantia nigra, but send
most of their output to the globus pallidus
The substantia nigra can be divided into two parts:
– substantia nigra pars compacta (SNpc)
– substantia nigra pars reticulata (SNpr)
– The SNpc receives input from the caudate and
putamen, and sends information right back.
The SNpr also receives input from the caudate
and putamen, but sends it outside the basal
ganglia to control head and eye movements.
– The SNpc is the more famous of the two, as it
produces dopamine, which is critical for
normal movement.
– The SNpc degenerates in Parkinson's disease.
The globus pallidus can also be divided into two parts:
– globus pallidus externa (GPe)
– globus pallidus interna (GPi)
– Both receive input from the caudate and
putamen, and both are in communication
with the subthalamic nucleus.
– It is the GPi, however, that sends the major
inhibitory output from the basal ganglia back
to thalamus.
– The GPi also sends a few projections to an
area of midbrain (the PPPA), presumably to
assist in postural control.
Basal Ganglia
• Principal neurotransmitters: ACh, GABA, and dopamine
• the overall effect on thalamus is inhibitory
• The function of the basal ganglia is often described in
terms of a "brake hypothesis"
• To sit still, you must put the brakes on all movements
except those reflexes that maintain an upright posture.
• To move, you must apply a brake to some postural
reflexes, and release the brake on voluntary movement.
• In such a complicated system, it is apparent that small
disturbances can throw the whole system out of whack,
often in unpredictable ways.
• The deficits tend to fall into one of two categories:
• the presence of extraneous unwanted
movements or
• an absence or difficulty with intended
movements.
Lesions of the Basal Ganglia
• Parkinson's disease: the slow and steady loss of
dopaminergic neurons in SNpc.
• The three symptoms usually associated with
Parkinson's are tremor, rigidity, and bradykinesia.
• The tremor is most apparent at rest.
• Rigidity is a result of simultaneous contraction of
flexors and extensors, which tends to lock up the limbs.
• Bradykinesia, or "slow movement", is a difficulty
initiating voluntary movement, as though the brake
cannot be released.
• Huntington's disease, or chorea, is a hereditary disease
of unwanted movements.
• It results from degeneration of the caudate and
putamen, and produces continuous dance-like
movements of the face and limbs.
• A related disorder is hemiballismus, flailing movements
of one arm and leg, which is caused by damage (i.e.,
stroke) of the subthalamic nucleus.
Cerebellum
Inputs and Outputs of the Cerebellum
The cerebellum operates in 3's:
1) there are 3 highways leading in and out of the
cerebellum: the peduncles or stalks
1) inferior
2) middle
3) superior
2) there are 3 main inputs
• mossy fibers from the spinocerebellar pathways
• climbing fibers from the inferior olive
• more mossy fibers from the pons, which are carrying
information from cerebral cortex
• The mossy fibers from the spinal cord have come up
ipsilaterally
• The fibers coming down from cerebral cortex, however,
DO need to cross (the cerebrum is concerned with the
opposite side of the body, unlike the cerebellum).
• These fibers synapse in the pons (hence the huge block
of fibers in the cerebral peduncles labeled
PLM Med Yr 2, Section C, Class 2012
Page 3 of 9
 "corticopontine"), cross, and enter the cerebellum as
mossy fibers.
3) and there are 3 main outputs from 3 deep nuclei
The 3 deep nuclei are:
a. Fastigial - primarily concerned with balance, and sends
information mainly to vestibular and reticular nuclei
b. Interposed
c. Dentate
• The dentate and interposed nuclei are concerned more
with voluntary movement, and send axons mainly to
thalamus and the red nucleus.
Cerebellum
• The cerebellum is involved in the coordination of
movement.
• it compares what you thought you were going to do
(according to motor cortex) with what is actually
happening down in the limbs (according to
proprioceptive feedback), and corrects the movement if
there is a problem.
• The cerebellum is also partly responsible for motor
learning e.g. riding a bicycle.
• Unlike the cerebrum, which works entirely on a
contralateral basis, the cerebellum works ipsilaterally.
Primary Motor System
Basic Motor Pathway
• The motor pathways are pathways which originate in
the brain or brainstem and descend down the spinal
cord to control the a-motor neurons.
• These large neurons in the ventral horns of the spinal
cord send their axons out via the spinal roots and
directly control the muscles.
• The motor pathways can control posture, reflexes, and
muscle tone, as well as the conscious voluntary
movements that we think of when we hear "motor
system".
• The most famous pathway is the so called "pyramidal
system", which begins with the large pyramidal
neurons of the motor cortex, travels through the
pyramids of the brainstem, and finally ends on or near
the a-motor neurons.
• This system is extremely important clinically, as strokes
often affect the motor system. Therefore it is crucial to
understand the anatomy of the motor pathway.
Apraxia
Three levels:
• Limb-kinetic:
– inability to use the contralateral hand
• Ideomotor:
– inability to perform an isolated motor act
upon command
• Ideational:
– inability to perform in organized sequence a
series of skilled acts
Motor System Pathway (figure – refer to ppt)
Autonomic Motor System
Parasympathetic: “deactivating”
Sympathetic: activating = fight or flight
Hypothalamus: controls appetite, rage, temperature, blood
pressure, perspiration, sexual drive
Association Systems
Basic Brain Organization
• Brainstem and reticular activating system: arousal and
attention
• Posterior cortex: perception and language
• Frontal cortex: generates programs and executes plans;
determines how the brain acts on its knowledge
• Korbinian Brodmann: 47 distinct cytoarchitectural areas
• Pierre Broca and Karl Wernicke: function localization
mapping
• DOMINANT and NON DOMINANT hemispheres:
Dominant Hemisphere process information in a
sequential, analytic, linear fashion, and efficient at
processing language and other symbolic information
Non Dominant Hemisphere- process information in a
gestalt , holistic, parallel fashion, and is particularly
efficient in processing visuospatial information.,
unconscious processing, Prosody
Language
Three-level processing in language comprehension:
1. Phonological processing (inferior gyrus of frontal lobes)
2. Lexical processing (left temporal lobe)
3. Semantic processing (middle and superior gyri of left
temporal lobe)
Mirror pathways on both hemisphere:
Right = pure language skills
Left = prosody
Limbic System
• Papez believed that the experience of emotion was
primarily determined by the cingulate cortex and,
secondly, by other cortical areas.
• Emotional expression was thought to be governed by
the hypothalamus.
• The cingulate gyrus projects to the hippocampus, and
the hippocampus projects to the hypothalamus by way
of the bundle of axons called fornix.
• Hypothalamic impulses reach the cortex via relay in the
anterior thlamic nuclei.
• Emotion is not a function of any specific brain center
but of a circuit that involves four basic structures,
interconnected through several nervous bundles : the
hypothalamus with its mamillary bodies, the anterior
thalamic nucleus, the cingulate gyrus and the
hippocampus.
• This circuit (Papez circuit), acting in an harmonic
fashion, is responsible for the central functions of
emotion (affect), as well as for its peripheral
expressions (symptoms).
• More recently, Paul McLean, accepting the essential
bases of Papez proposal, created the denomination
limbic system and added new structures to circuit : the
orbitofrontal and medialfrontal cortices (prefrontal
area), the parahippocampal gyrus and important
subcortical groupings like the amygdala, the medial
PLM Med Yr 2, Section C, Class 2012
Page 4 of 9
 thalamic nucleus, the septal area, prosencephalic basal
nuclei (the most anterior area of the brain) and a few
brainstem formations.
Structures:
Amygdala Hypothalamus
Cingulate Gyrus Olfactory cortex
Fornix Thalamus
Hippocampus
Amygdala
• If you remember only one word about the amygdala,
the word is FEAR.
• The amygdala is the nucleus responsible for the lurch
you feel in your stomach when you turn around in a
dark alley and notice someone following you.
• It couples a learned sensory stimulus (man in ski mask
in alley = danger) to an adaptive response (fight or
flight).
• Inputs:
the amygdala must get sensory input, and it must be fairly highly
processed input to recognize the elements of a scene that signal
danger. The association areas of visual, auditory, and
somatosensory cortices are the main inputs to the amygdala.
• Outputs:
the amygdala must be able to control the autonomic system, to
provoke such an instant sympathetic response. The main outputs
of the amygdala are to the hypothalamus and brainstem
autonomic centers, including the vagal nuclei and the
sympathetic neurons.
• The amygdala is also involved with mood and the
conscious emotional response to an event, whether
positive or negative. To this end, the amygdala is also
extensively interconnected with frontal cortex,
mediodorsal thalamus, and the medial striatum.
Memory
• There are at least three different types of memory.
• The most short term is working memory.
• Working memory is like the RAM of a computer. It is
the type of memory that enables you to spit back the
last sentence of a conversation when someone accuses
you of not listening.
• Like the RAM of a computer, it is crucial for performing
some common operations in your head: adding
numbers, composing a sentence, following directions,
etc.
• Also like a computer, the space devoted to that
operation is recycled as soon as you turn to something
else.
• It does not become a permanent memory.
• Working memory does not require the hippocampus; it
is probably a cortical phenomenon.
Hippocampus and Memory
• The second type is what we most commonly associate
with "memory".
• This is long-term or declarative memory, and is
composed of all the facts, figures, and names you have
ever learned.
• All of your experiences and conscious memory fall into
this category.
• It is analogous to the hard drive of a computer.
• Although no one knows exactly where this enormous
database is stored, it is clear that the hippocampus is
necessary to file away new memories as they occur.
• The third type is procedural memory, and is probably
the most durable form of memory.
• These are actions, habits, or skills that are learned
simply by repetition.
• Examples include playing tennis, playing an instrument,
solving a puzzle, etc.
• The hippocampus is not involved in procedural
memory, but it is likely that the cerebellum plays a role
in some instances.
• Therefore, the hippocampus is critical in laying down
declarative memory, but is not necessary for working
memory, procedural memory, or memory storage.
• Damage to the hippocampus will only affect the
formation of new declarative memories.
Prefrontal Area
• This area comprises the entire non-motor anterior
region of the frontal lobe.
• It underwent a great deal of development during the
evolution of mammals.
• It is specially large in man and in some species of
dolphins.
• It does not belong to the traditional limbic circuit, but
its intense bi-directional connections with thalamus,
amygdala and other subcortical structures, account for
the important role it plays in the genesis and, specially,
in the expression of affective states.
• When the pre-frontal cortex suffers a lesion, the subject
looses his sense of social responsibility as well as the
capacity for concentration and abstraction. In some
cases, although consciousness and some cognitive
functions, like speech, remain intact, the subject can no
longer solve problems, even the most elementary ones.
• When pre-frontal lobotomy was used for treatment of
certain psychiatric disturbances, the patients entered
into a stage of "affective buffer", no longer showing any
sign of joy, sadness, hope or despair.
In their words or attitudes, no traces of affection could be
detected.
Psychiatric Implications
• Four A of schizophrenia = brain functions subserved in
part by limbic structures
• Reduced gray matter volume (hippocampus, amygdala,
parahippocampus)
• Decreased frontal lobe activation
• Activation of the same areas for spoken language as
that in auditory hallucination
• Frontal lobe injury impairs executieve functions:
motivation, attention, sequencing of actions
• Frontal lobe injury impairs executive functions:
motivation, attention, sequencing of actions
• frontal lobe syndrome: slowed thinking, poor judgment,
decreased curiosity, social withdrawal, irritability
Neural Development
• Migration to adult sites
• Heterotopia (incorrectly placed neurons)
• Auditory processing and language:
PLM Med Yr 2, Section C, Class 2012
Page 5 of 9
 – Temporally determined perceptual map of
phonemes
– Nueronal location of specific sounds differ
across cultures (difficulty of Japanese to
distinguish “la” from “ra”)
– Very early experiences may establish the
density and fidelity of neural circuits for
specific functions
Psychiatric Implications
• nature and nurture
• Milieu affects neural development such that a person
may either be:
– given an advantage (e.g. musically exposed
being better at mathematics and spatial
reasoning)
– or disadvantaged (e.g. pattern of trauma or
fear flood amygdala to be specifically alert to
threatening stimuli; or chaos for poor
acquisition of complex cognitive skills later)
• Tantalizing basis for development theories
• Early experiences primes the basic circuitry for
language, emotion, and other advanced behaviours
Neurophysiology and Neurochemistry
(see figures in ppt)
Synaptic Transmission
• Synaptic transmission = propagation of nerve impulses
from one nerve cell to another.
• Neurotransmitter release into synaptic space = nerve
impulses transmission
• Synapse = junction at which the axon of the presynaptic
neuron terminates at some location upon the
postsynaptic neuron.
• Terminal button = enlarged structure at end of a
presynaptic axon, where it is juxtaposed to the
postsynaptic neuron
• An axon can make contact anywhere along the second
neuron:
– on the dendrites (an axodendritic synapse)
– on the cell body (an axosomatic synapse)
– on the axons (an axo-axonal synapse).
• The neurotransmitters are a diverse group of chemical
compounds ranging from simple amines such as
dopamine and amino acids such as gaminobutyrate
(GABA), to polypeptides such as the enkephalins.
• The mechanisms by which they elicit responses in both
presynaptic and postsynaptic neurons are as diverse as
the mechanisms employed by growth factor and
cytokine receptors.
(see figures on ppt)
Presynaptic Components
• voltage gated calcium channels locally raise intracellular
Ca concentration and initiates cascade of interaction
• neurotransmitter containing vesicles fuse with the
presynaptic membrane and undergoes exocytosis
• neurotransmitter diffuse into cleft and binds to specific
receptors on external membrane of the postsynaptic
neuron.
• Tansmembrane transporter molecules return free
Mono Amine NT to nerve terminals where they are
repackaged into vesicles for release or degraded by
MAO.
(Mao type A metabolize Norepinephrine and Serotonin and
its inhibition by Mao inhibitors is associated with mood
elevation. Mao B metabolize Dopamine)
Postsynaptic Components
Receptors are the site of action of most available
psychoactive substances.
Principal functions of these receptors- to alter electrical
transmembrane potential to either increase or decrease
likelihood of triggering an action potential
Sensitivity of receptors are due to
a. number of receptors present
b. affinity of the receptor for the neurotransmitter
c. efficiency of translation of both neurotransmitter and
receptor into a neuronal message
• G Proteins
• Second Messengers
– Cyclic Nucleotides
– Calcium
– Phosphoinositol Metabolites
– Eicosanoids
– JAK-STAT
• Protein Kinases
Neurotransmitter Receptors
• Once the molecules of neurotransmitter are released
from a cell as the result of the firing of an action
potential, they bind to specific receptors on the surface
of the postsynaptic cell.
• In all cases in which these receptors have been cloned
and characterized in detail, it has been shown that
there are numerous subtypes of receptor for any given
neurotransmitter.
• As well as being present on the surfaces of postsynaptic
neurons, neurotransmitter receptors are found on
presynaptic neurons.
• In general, presynaptic neuron receptors act to inhibit
further release of neurotransmitter.
• The vast majority of neurotransmitter receptors belong
to a class of proteins known as the serpentine
receptors.
• This class exhibits a characteristic transmembrane
structure: that is, it spans the cell membrane, not once
but seven times.
• The link between neurotransmitters and intracellular
signaling is carried out by association either with G-
proteins (small GTP-binding and hydrolyzing proteins)
or with protein kinases, or by the receptor itself in the
form of a ligand-gated ion channel (for example, the
acetylcholine receptor).
• One additional characteristic of neurotransmitter
receptors is that they are subject to ligand-induced
desensitization: That is, they can become unresponsive
upon prolonged exposure to their neurotransmitter.
• The molecule is synthesized in the neuron
PLM Med Yr 2, Section C, Class 2012
Page 6 of 9
 • The molecule is present in the presynaptic neuron and Metabolism of Catecholamine Neurotransmitters
is released on depolarization in physiologically
significant amounts
• When administered exogenously as a drug, the
exogenous molecule mimics the effects of the
endogenous neurotransmitter
• A mechanism in the neuron or the synaptic cleft acts to
remove or deactivate the neurotransmitter
• The molecule is synthesized in the neuron
• The molecule is present in the presynaptic neuron and
is released on depolarization in physiologically
significant amounts
• When administered exogenously as a drug, the
exogenous molecule mimics the effects of the
endogenous neurotransmitter Dopaminergic pathway
• A mechanism in the neuron or the synaptic cleft acts to • The first is the mesolimbic pathway–the bundle of
remove or deactivate the neurotransmitter dopaminergic fibres associated with the reward circuit.
• This pathway originates in the ventral tegmental area
Transmitter Molecule Derived From Site of Synthesis and innervates several structures of the limbic system,
including the nucleus accumbens.
CNS, • The mesolimbic pathway is important for memory and
Acetylcholine Choline parasympathetic for motivating behaviours.
nerves • By blocking this pathway, antipsychotic drugs reduce
the intense emotions caused by conditions such as
Serotonin CNS, chromaffin schizophrenia.
• The mesocortical pathway also originates in the ventral
5-Hydroxytryptamine Tryptophan cells of the gut,
tegmental area, but projects to the frontal cortex and
(5-HT) enteric cells surrounding structures.
• Some evidence indicates that a malfunction in this
GABA Glutamate CNS pathway might be the cause of some of the symptoms
of schizophrenia, such as hallucinations and disordered
Glutamate CNS thinking.
• Medications that block this pathway reduce psychotic
Aspartate CNS delirium, but also reduce the overall activity of the
frontal lobes.
Glycine spinal cord • The third, nigrostriatal pathway projects axons from
the substantia nigra to the striatum (caudate nucleus
Histamine Histidine hypothalamus and putamen), which is involved in motor control.
Degeneration of the neurons in this pathway is
Epinephrine synthesis adrenal medulla, associated with the trembling and muscular rigidity
Tyrosine symptomatic of Parkinson’s disease.
pathway some CNS cells
• A fourth dopaminergic pathway worth mentioning is
the tuberoinfundibular pathway, which connects the
Norpinephrine CNS, sympathetic
Tyrosine hypothalamus to the pituitary gland, where it
synthesis pathway nerves influences the secretion of hormones such as prolactin
Serotonin
Dopamine synthesis • naturally produced in the Pineal gland which lies deep
Tyrosine CNS
pathway at the centre of the human brain.
• The average adult human possesses only 5 to 10 mg of
CNS, periperal serotonin, 90 % of which is in the intestine and the rest
Adenosine ATP in blood platelets and the brain.
nerves

sympathetic, Involved in the control of

• Appetite
ATP sensory and enteric
• Sleep
nerves • memory and learning
• temperature regulation
CNS, • Mood
Nitric oxide, NO Arginine gastrointestinal • Behaviour
tract • cardiovascular function
• muscle contraction
PLM Med Yr 2, Section C, Class 2012
Page 7 of 9
 • endocrine regulation
• depression
(see figures of ‘serotonin nerve pathways in the brain’ on ppt)
GABA
• Several amino acids have distinct excitatory or
inhibitory effects upon the nervous system. The amino
acid derivative, g-aminobutyrate, also called 4-
aminobutyrate, (GABA) is a well-known inhibitor of
presynaptic transmission in the CNS, and also in the
retina. The formation of GABA occurs by the
decarboxylation of glutamate catalyzed by glutamate
decarboxylase (GAD). GAD is present in many nerve
endings of the brain as well as in the b-cells of the
pancreas. Neurons that secrete GABA are termed
GABAergic.
• Several amino acids have distinct excitatory or
inhibitory effects upon the nervous system. The amino
acid derivative, g-aminobutyrate, also called 4-
aminobutyrate, (GABA) is a well-known inhibitor of
presynaptic transmission in the CNS, and also in the
retina. The formation of GABA occurs by the
decarboxylation of glutamate catalyzed by glutamate
decarboxylase (GAD). GAD is present in many nerve
endings of the brain as well as in the b-cells of the
pancreas. Neurons that secrete GABA are termed
GABAergic.
• GABA exerts its effects by binding to two distinct
receptors, GABA-A and GABA-B. The GABA-A receptors
form a Cl- channel. The binding of GABA to GABA-A
receptors increases the Cl- conductance of presynaptic
neurons. The anxiolytic drugs of the benzodiazepine
family exert their soothing effects by potentiating the
responses of GABA-A receptors to GABA binding. The
GABA-B receptors are coupled to an intracellular G-
protein and act by increasing conductance of an
associated K+ channel.
Monoamine neurotransamitters
• present in only a small percentage of neurons localized
in small nuclei of the brain
• have enormous impact on total brain functioning
because the diffuse projections of axons from these
monoaminergic neurons can affect virtually every brain
region.
Amino Acids
Most abundant neurotransmitter
1. GaBa – major inhibitory N. ( Bzd act on this mechanism)
2. Glutamate- major excitatory N. NMDA is the most understood
receptor of glutamate and has a role in learning memory and
psychopathology :
psychosis , Schizophrenia
• and it is possible to conceptualize the brain as reflecting
the balance between the excitatory amino acid
glutamate, and the inhibitory amino acid g-
aminobutyric acid
• all existing drugs for psychiatric conditions act through
monoamine or amino acid neurotransmitter systems
Peptides
A. Endogenous opiods
1. involved in regulation of stress, pain, mood
2. Endogenous opiods :
enkephalins, endorphins, dynorphins
3. effects of neurotransmission in hippocampus:
contributes to addiction
B. Substance P
1. Primary neurotransmitter in sensory neurons &
strianigral pathway; associated with mediation
of pain
C. Cholecystokinin
involved in pathophysiology of Schizophrenia,
eating and movement disorders
Somatostatin
1. growth hormone inhibiting factor
2. implicated in Huntington’s disease, Alzheimer’s
dementia
Vasopressin and Oxytoxin
1. synthesized in the hypothalamus
2. mood regulation
Neuropeptide Y
1. stimulate appetite
2. area of interst in Obesity
Nucleotides
Purine adenosine inhibits the release of other neurotransmitters
and ATP
Gasses
Nitric Oxide acts as both intraneuronal second messenger and
neurotransmitter. With excessive exposure to glutamate Nitric
Oxide is metabolized to toxic free radicals which may injure or
kill cells through excitotoxicity
Eicosanoids
Anandamides
Sigma receptors
Neurotrophic factors
• Growth factors that allow neurons to regenerate their
axon are also called neurotrophic factors. NGF (Nerve
Growth Factor) is the most widely-known. Recently,
other factors have been identified, such as BDNF (Brain-
Derived Neurotrophic Factor), CNTF (Ciliary
Neurotrophic Factor), GDNF (Glial Cell-line
Neurotrophic Factor), and IGF (Insulin Growth Factor),
to name only a few.
Neurotransmitters:
• Neurons can also be classified according to the
neurotransmitters they contain (e.g., the dopamine
neurons of the substantia nigra).
• neurotransmitters have defined effects on the activity
of neurons, whereas complex brain functions, such as
those disturbed in psychiatric disorders, are mediated
by the coordinated activity of ensembles of neurons.
• effects of neurotransmitters on behavioral, emotional,
or cognitive states must be viewed within the context
of the neural circuits that they influence.
Genetics and Brain Development
PLM Med Yr 2, Section C, Class 2012
Page 8 of 9
Alterations in gene expression occur both during development
and in adulthood and may be the bases for abnormal and normal
development, and for abnormal and normal adaptation to stress
The normal affective, cognitive, and behavioral processes that are
disturbed in different psychiatric disorders arise because of
specific patterns of activation in networks of neurons that are
distributed through the central nervous system. These patterns of
activation are mediated by the connections among specific brain
structures.
• Every function of the human brain is a consequence of
the activity of specific neural circuits. The circuits form
as a result of several developmental processes
• In early development, some axons initially produce an
excessive number of axon branches or collaterals and
thus contact a broader set of targets than are present in
the adult brain
• During later development the connections of particular
neurons are focused by the pruning or elimination of
axonal projections to inappropriate targets.
• the role of any particular brain region or group of
neurons in the production of specific behaviors or in
the pathophysiology of a given neuropsychiatric
disorder but must be considered within the context of
the neural circuits connecting those neurons with other
brain regions.
Illnesses in the Brain cannot be viewed in isolation
Population Genetics
provided some of the first objective data that mental
illnesses were biological illnesses, thereby helping to
destigmatize these human conditions
application of molecular neurobiological tools led to the
ability to study specific genetic linkages among individuals
and groups of individuals
application lead to the identification of a specific gene or
genes as causative agents for specific mental disorders.
Psychoneuroendocrinology
• Endocrine disorders are frequently associated with
secondary psychiatric symptoms (e.g. depression)
• A significant percentage of patients suffering from
psychiatric syndromes display regular patterns of
endocrine dysfunction
• The interactions between the neuroendocrine and
central nervous systems:
1. psychiatric symptoms that accompany some hormonal
disorders (e.g., depression in Cushing's syndrome)
2. In the identification of disorders wherein
neuroendocrine regulation is utilized as potential
markers for state or trait variables in psychiatric
conditions
• Pathological alterations in hypothalamic-pituitary-
adrenal function have been associated with mood
disorders, posttraumatic stress disroder, Alzheimer’s
dementia, substance use disorders
• Insulin: depression common in DM
• Hypothalamic-pituitary-gonadal axis
– Testosterone: increased violence and
aggression, mood improvement, sexual desire
– Estrogen: mood enhancement
– Increased Prolactin: depression, decreased
libido, stress intolerance, anxiety, increased
irritability
• Hypothalamic-pituitary-thyroid axis
– Neuronal excitability, behaviour,
neurotransmitter regulation
– Hyperthyroidism: fatigue, irritability,
insomnia, anxiety, restlessness, weight loss,
emotional lability, impairment in
concentration and memory
– Hypothyroidism: fatigue, decreased libido,
memory impairment, irritability, suicidal
ideation
Psychoneuroimmunology
• Classical conditioning paradigms have been associated
with suppression or enhancement of the immune
response
• Stressful life events can increase susceptibility to
infectious diseases
• Academic/examination stress in medical students
showed decreased natural killer cell activity, T cells,
mitogen responses, interferon production, impaired
cellular immunity
Biological Rhythms and Chronobiology
• circadian rhythms are set by zeitgebers principally
emanating from pontine reticular formation and
suprachiasmatic nuclei of the hypothalamus
• Phase advance or phase delay
• Depression is the most commonly associated symptom
in biological rhythm disruption
Conclusion
• understanding the neurobiological bases for psychiatric
disorders requires an appreciation of the major
principles governing the functional organization and
connections in the human brain.
PLM Med Yr 2, Section C, Class 2012
Page 9 of 9