Physiology of Learning

dr. Legiran, M.Kes

- S1 FK Unsri Palembang
- S2 Anatomi PPs UGM Yogyakarta
- Sekretaris Bagian Anatomi
- Komisi IV Unit Pengembangan dan Evaluasi

Pendidikan (UPEP)

Memory
Place to store information, as in: How much

memory does your hard drive have?

Information that gets stored, as in: I have fond

memories of my summer vacation.

retention of learned information

Learning: acquisition of knowledge/information

The Modal Model of Human Memory

Memory stores
Sensory Memory

Short-Term
Memory

Long-Term
Memory

Capacity

Very large

72 items

Infinite

Duration

Very short
(Fraction of
second)

Short (Fraction
Indefinite
of minute)

Format
(Coding)

Direct
representation of
sensual
experience as
action potentials

Spoken
language
format

Semantic
(meaningful)
format

Processes
Attention

Selects portion of Sensory Memory for further processing by

STM
Ex: Attend to lecture, not sound of ventilation system.

Chunking

Group items into meaningful units

Strategy to increase capacity of STM
Ex: 270-348-8-0-8-0

Rehearsal

Repeat information until no longer needed.

Strategy to increase duration of STM
Ex: 8080 8080 8080Oops, what was that number?

Encoding

Information moved from STM to LTM.

Ex: Studying to learn the answers to the test questions.

Retrieval

Information moved from LTM to STM

Ex: Remembering the answer to the question so that you can
write it down.

Four Theories of Forgetting from Long-Term

Memory
Explanation

Description

Example

Encoding
Failure

Information never encoded

from
STM to LTM.

Student studies for exam while

watching TV, cant remember
answers to test questions.

Decay

Information encoded in
LTM, but decays over time
with lack of use.
However, some memories
never decay, even though
they are not frequently used.
Decay can be explained by
interference.

Ebbinghaus memorized nonsense

words, tested his memory of these
days later, found forgetting
curve.

Four Theories of Forgetting (contd)

Explanation

Interference

Repression

Description
Information encoded in
LTM, but cannot be retrieved
because newer
information interferes.
Can be thought of as
retrieval error.
Accounts for Ebbinghauss
findings, without memories
decaying.
According to Freud, painful
memories can be pushed
below level of consciousness.
Very controversial topic;
many psychologists now
argue that repression does not
occur.

Example

Cant remember old phone

number; recall new number
instead.

Memories of child abuse suddenly

recalled during psychotherapy
(But are they accurate?)
Recovered Memory Syndrome
false memories planted during
hypnosis or drug therapy.
Loftuss Lost in the Mall
experiment.

Types of LTM

Memory and learning

Types of memory:

declarative
facts and events
conscious recollection
easy come easy go

procedural

learning to play an instrument, to ride a bike;

no conscious recollection (usually);
need repetition or training;
longer retention

Memory and learning

Subtypes of declarative memory:

short-term memory
temporary,
limited capacity,
needs rehearsal (e.g. telephone number)

long-term memory
'permanent'
greater capacity
no continual rehearsal needed

Theories of memory storage

Engram
Engram was a hypothetical structure or feature inside
of the neuron that stored information
Grandmother cell the neuron that fired when you
see your grandmother
In computers, information (memories) stored in
cells or slots of hard drive
But this is not how the nervous system stores
information!

Theories of memory storage

Long-Term Potentiation (LTP)
Recent research indicates that memories are stored in
the synapses between neurons
Learning involves formation and modification of
synapses
Neurons that fire together wire together
LTP takes days to complete learning spaced over
several days more effective at inducing LTP than
learning crammed into short period of time
Most research on LTP done on sea slug Aplysia

Memory
Thompson
many structures involved in memory formation;
memory depends on many mechanisms;
classical conditioning of eyelid responses in rabbit response
occurs in cerebellum - lateral interpositus nucleus (LIP)

Memory and learning

Plasticity paradigms:

Associative mechanisms:
classical conditioning
pairing of 2 stimuli changes the response to one of them (Pavlov)
conditioned stimulus (CS) - originally neutral (no response)
unconditioned stimulus (UCS) - automatically evokes
response unconditioned response (UCR)

after repetitive pairing of CS and UCS presentation of CS

evokes learned response - conditioned response (CR)

operant conditioning - reinforcement and punishment

Memory and learning

Nonassociative mechanisms:
habituation
decrease in response to a repeated stimulus not accompanied
by changes in other stimuli
sensitisation
an increase in response to a moderate stimuli as a result of a
previous exposure to a strong stimulus

Memory and learning

memory consolidation - storing knowledge in the
long-term memory
Hebb - reverberating circuit - prolonged excitation leads to
chemical or structural changes
Memory of meaningful or emotional facts enhanced
involvement of amygdala (stimulation of hippocampus and
cortex)
damage to amygdala impairs emotional enhancement of
memories

Memory and learning

working memory - modification of the concept of
short term memory
memory consolidation may take place with or without use of
the short-term memory
a phonological loop
a visuo-spatial sketchpad
the central executive - directs attention towards stimuli;
determines what will be stored in the working memory
working memory test - delayed response task - higher activity
in the prefrontal cortex during the delay

Physiology of Memory
Types of amnesia
1. Retrograde amnesia

Loss of memories already formed due to brain damage

But can still form new LTMs
Example: Patient has stroke and no longer recognizes
family members.
Common symptom of Alzheimers disease

Physiology of Memory
Types of amnesia
2. Anterograde amnesia

Loss of ability to form new long-term memories

Previously stored memories may still be intact
Korsakoffs syndrome You meet patient, tell him
your name, he can repeat it You leave room, come
back 2 minutes later, he doesnt know who you are.

Hippocampus
Thought to play a role in encoding information

from STM to LTM

Case of H.M.

Both hippocampi removed to control severe epilepsy

No problems with short-term memory
Lost ability to form new long-term memories
(anterograde amnesia)
LTM intact for events until shortly before surgery
Symptoms similar to Korsakoffs syndrome, but
different area of brain affected

Memory and learning

Hippocampus

H. M. - removal of hippocampus:
Retrograde amnesia (loss of memory for events occurring
shortly before brain damage)
intact short-term/working memory
acute anterograde amnesia (declarative memory) (loss of
memory for events happening after the brain damage)
intact procedural memory
better implicit than explicit memory

Memory and learning

Theories of the hippocampal function:

declarative, explicit memory

supported by the H.M. case
hippocampal damage may impair implicit memory
it does not damage all the memory in nonhumans in tasks
similar those requiring declarative memory from humans

dependence on the experimental protocol in delayed

matching-to-sample

and

sample task experiments

delayed

nonmatching-to-

Memory and learning

spatial memory
rat maze experiments
hippocampus is involved also in nonspatial aspects of the tasks

configural learning
the meaning of the stimulus depends on what other stimuli are
paired with it, e.g. A + food; B + food; AB + no food
hippocampus is involved in nonconfigural learning if its
sufficiently difficult

binding memories
input from many parts of cortex (secondary and tertiary areas)

Memory and learning

Brain damage and memory
Korsakoff's syndrome brain damage due to prolonged
deficiency in thiamine (B1).
Thiamine deficiency

loss of neurons in dorsomedial thalamus

damage to prefrontal cortex

apathy, confusion, retrograde and anterograde amnesia;
better implicit memory (good at priming tasks);
impaired reasoning about own memories;
confabulation;

Memory and learning

Alzheimer's disease
forgetfulness, proceeding into serious memory loss
confusion, depression, restlessness
hallucinations
sleeplessness, loss of appetite
impaired procedural memory, explicit memory, attention.
Genetic involvement;
excessive accumulation of beta-amyloid plaques
atrophy of cerebral cortex (esp. entorhinal), hippocampus
formation of neurofibrillary tangles

Memory and learning

Physiology of learning and memory
Hebbian learning
a cell A that successfully stimulated cell B in the past becomes
more successful in the stimulation of B in the future

Hebbian learning and classical conditioning

Single cell mechanisms of invertebrate plasticity
Aplysia

Memory and learning

habituation depends on a change in synapse between
the sensory and motor neuron

Memory and learning

Sensitisation
strong skin stimulation
excitation of facilitating interneuron
serotonine release on presynaptic terminals of sensory neurons
metabotropic effects
prolonged action potential
longer opening of voltage-gated calcium channels
greater transmitter release per action potential

Memory and learning

associative learning
similar to the sensitisation
pairing the CS and US increases presence of calcium in the
presynaptic terminal (due to CS)
Intensified metabotropic effects
More transmitter released than in sensitisation

Memory and learning

Physiology of vertebrate plasticity

long term potentiation (LTP)

a response enhancement at certain synapses due to rapid
intensive stimulus delivered simultaneously to a neuron by
several axons
underlying mechanisms vary between the brain areas
prominent in hippocampus
attractive as a cellular basis of learning and memory :
Specificity only the active synapses become strengthened
Cooperativity simultaneous (almost) stimulation produces LTP
Associativity LTP is hebbian (no need for action potential
depolarisation sufficient)

Memory and learning

Biochemistry of LTP main actors:
Glutamate receptors
AMPA opens sodium channels
NMDA allows sodium and calcium ions to enter the neuron
responds to glutamate ONLY when the membrane is partly
depolarised
removal of magnesium ions blocking NMDA
receptors
glutamate excitation of NMDA receptors opens NMDAdependent calcium channels

Memory and learning

large influx of calcium activates protein kinases:
protein kinase C (PKC)
CaMKII (calcium calmodulin-dependent protein
kinase)
alteration the structure (phosphorylation) of AMPA receptors
conversion of some NMDA receptors into AMPA receptors
creation of more AMPA receptors
increased dendritic branch growth
increased dendritic responsiveness to subsequent incoming of
glutamate

Memory and learning

Long term depression (LTD)
a prolonged decrease in response to synaptic input
repeatedly paired to another input at a low frequency
LTP (LTD) may be involved in memory formation recently questioned

Memory and learning

Potential problems with LTP/LTD as correlates of
memory formation:
Importance of protein phosphorylation
Protein phosphorylation is not permanent
protein molecules are not permanent (app. 2 weeks lifetime)

Memory and learning

Alternative mechanisms:
continual phosphorylation of proteins
main suspect: persistently active protein kinases (PKC)
large elevation of calcium activates calpain (enzyme)
breaking the peptide bond between regulatory and
catalytic parts of PKC
freeing the catalytic region (remains active) leading to
continual proteins phosphorylation
problem with PKC solution limited time (minutes to
hours but Bruces work)

Memory and learning

protein synthesis
evidence from experiments with protein synthesis
inhibitors
animals injected with these inhibitors learn normally
but fail to recall during later testing
structural changes
change in the number of synapses
morphological reorganisation