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Physiology of Memory and Learning

Memory an LearningMemory an Learning

Learning and memory are higher-level functions of the nervous system.

Learning is the neural mechanism by which a person changes his or her behavior as a result of experiences.

Memory is the mechanism for storing what is learned.

LearningLearning ♦ DefIt is the ability of previous experiences to modify the inborn

reactions or create new ones or It is the acquisition of knowledge or skills as a result of experiences

and consequently it can alter behavior on basis of this experiences Learning is the process by which we acquire knowledge about the

world (Eric Kandel, 2000)Learning refers to a more or less permanent change in behavior which

occurs as a result of practice (Kimble, 1961)

LearningLearning Types

Associative LearningAssociative Learning In this type of learning, the subject learns about the

relationship that can associate one stimulus to another It is a conditioned process which results in the

formation of learned responses called conditioned reflexes

Conditioned reflex is an automatic response to a stimulus (conditioned stimulus) which did not previously evoke response acquired by repeatedly associating this stimulus with another stimulus (unconditioned stimulus)

a) Classic Conditioninga) Classic ConditioningThis type of conditioned reflexes was 1st described

by Pavlov (Russian Physiologist) He noticed that his experimental dogs salivate just

on seeing the animal house keeper who used to feed Some sort of association had developed in the brains

of these animals between visual stimuli related to seeing the housekeeper (conditioned stimulus) and food ingestion (unconditioned stimulus for salivation when food is placed in mouth)

a) Classic Conditioninga) Classic Conditioning

a) Classic Conditioninga) Classic ConditioningThis type of conditioning can be integrated a

different levels of CNSRequirements:1) CS applied before US2) Pairing must occur several times 3) No separation between the CS and US

a) Classic Conditioninga) Classic Conditioning

b) Operant Conditioningb) Operant ConditioningIn this type of conditioning the subject is taught to

perform some voluntary action in response to a particular stimulus (visual or sound stimulus) that alert him to perform the learned action in order to obtain reward to avoid punishment

Alerting signal acts as conditioned stimulus whereas pleasant or unpleasant event that follow performance of learned response represents unconditioned stimulus

b) Operant Conditioningb) Operant Conditioning

b) Operant Conditioningb) Operant Conditioning

Example:Car driver and traffic light The car driver stops the car on seeing the red traffic light and drives on seeing the green light

Integration:Hippocampus and amygdala are important in linking the stimulus to the operation Integration occurs in CC especially orbitofrontal cortex

Non-associative LearningNon-associative Learning In this type of learning, the subject learns whether

to ignore or react to a certain stimulus It is a simple way of learning that does not need

association between 2 stimuliIt is 2 types;A) HabituationB) Sensitization

HabituationHabituation It is a gradual decrease in the response to stimulus

when it is frequently repeated It is simple and widespreadExamples:A loud and unexpected sound produces looking

towards the source of sound, change in heart rate, and change in blood pressure

If the sound turns to be insignificant, its repetition results in little or no response

HabituationHabituation It is a stimulus specific e.g. traffic noise and mother

and babyMechanism:Repetition of the stimulus close Ca channels in

presynaptic neurons →↓ Ca influx →↓ release of neurotransmitters →↓ behavioral responses to the stimulus

HabituationHabituation Experiments performed in Aplysia californica

SensitizationSensitization It is a potentiation in the response to stimulus (painful

or pleasant) when it is frequently repeated It is simple and widespreadExamples:One normally ignore stray dogs by habituation, but if

he is bitten, he will become more attentive and develop aversion reaction to them for long time

Stimulus specific:One who is bitten by dogs will not be afraid of

donkeys or cows

SensitizationSensitization Mechanism:Strong or noxious stimulus → facilitating

interneurons (serotonin) →↑ cAMP in presynaptic neurons → block of K channels → depolarization of presynaptic neurons → keep Ca channels open →↑ Ca influx →↑ release of neurotransmitters →↑ behavioral response to mild stimuli

SensitizationSensitization

SensitizationSensitization

MemoryMemory Def memory is the process by which that knowledge of the world

is encoded, stored, and later retrieved (Kandel (2000), Memory is a phase of learning

learning has three stages: 1. acquiring, wherein one masters a new activity . . . or memorizes verbal material . . . 2. retaining the new acquisition for a period of time; and 3. remembering, which enables one to reproduce the learned act or memorized material

MemoryMemory Def It is the ability of the brain to store information and recall it

at later time or

Capacity of the brain: It is limited (total capacity of brain is 3x 108 bits) So, informations entering brain are either;

A.Selected and stored (1%) → most important

B.Other (99%) → are neglected and forgotten

MemoryMemory Information Unit: It is bit A bit is the simplest form of sensory experience i.e. figure,

sound, touch , or smell All sensory systems send information to brain at 50 bit/sec E.g. during reading 40 bits/sec, during mental calculation 12

bits/ sec, and during counting 3 bits /sec Average rate of flow of information is 20 bits/sec For learning a language about 40- 50 millions bits should be

stored in memory To store 1 bit, 10 neurons are required

MemoryMemory Classification of memory:

11 . .Sensory MemorySensory Memory• Duration: very short (about 0.5 seconds)• Capacity: very small (15-20 bits)• Entry into storage: automatic during perception• Access to storage: very rapid 1. Vision: iconic memory

2. Hearing: echoic memory

• Mechanism: • 1. Stimulation of reverberating circuits → repeated

activation of neurons • 2. Synaptic sensitization if sensory experience coupled with

painful stimuli

11 . .Sensory MemorySensory Memory

• Mechanism:• 3. Posttetanic potentiation: multiple stimuli at

presynaptic terminal →↑ Ca content in presynaptic terminal →↑ release of neurotransmitters

• Mechanism of forgetting: • 1. Fading (spontaneous and gradual decline in the amount

of information)• 2. Extinction (spont. disappearance of information from

memory)

2. Short-term Memory2. Short-term MemoryDuration: (min to hours) Capacity

– Small bits of informations – Miller’s magical number: 7±2 chunks of information

Entry into storage: verbalization (describing the items in words)

Recall or access to storage: rapid Mechanism: Made by formation of temporary memory traces

2. Short-term Memory2. Short-term MemoryMemory trace: Is a newly developed pathway or signal transmission

resulting from facilitation of new synapses → creation of new circuits in the brain

This occurs by 1. Long term potentiation of synapses 2. Changes in physical properties of postsynaptic

membrane → ↑ sensitivity to chemical transmitters Mechanism of forgetting: New information replaces old

3. Long-term Memory3. Long-term MemoryDuration: (hours to years ) Capacity

– Very large – Information stored according to its significance

Entry into storage: practice or and punishment or reward

Recall or access to storage: slow Mechanism: Made by formation of memory engrams (long-

lasting memory traces) formed by structural changes in presynaptic terminals

Long-term potentiationLong-term potentiation 1. The binding of glutamate to its NMDA receptors and

simultaneous depolarization of the postsynaptic membrane causes the NMDA receptor channels to open.

2. This opening of the NMDA receptor channels allows Ca2+ to enter.

3. The entry of Ca2+ into the postsynaptic neuron causes long-term potentiation in that neuron.

4. The entry of Ca2+ into the postsynaptic neuron also activates nitric oxide synthase, causing nitric oxide production.

5. The nitric oxide then acts as a retrograde messenger, diffusing into the presynaptic neuron and somehow causing it to release more neurotransmitter.

3. Long-term Memory3. Long-term MemoryMechanism: memory engrams made up by;1. increase in number of vesicles2. increase in number of presynaptic terminals3. increase in release sites of chemical transmitters4. generation of new receptor sites 5. long term potentiation Engrams remain for long time up to several yearsFormation of new engrams requires protein

synthesis

3. Long-term Memory3. Long-term Memory

Mechanism of forgetting:

1. Proactive inhibition by previously stored materials (more common)

2. Retroactive inhibition by subsequently stored material

4. Permanent Memory4. Permanent Memory

Duration: (permanent) Capacity

– Very large

Entry into storage: very frequent practiceRecall or access to storage: very rapid (recall not

affected by brain injury (like name, write, and read) Mechanism: Advanced stage of long-term(permanent engrams)

Mechanism of forgetting : No forgetting

Phases of memoryPhases of memory Encoding-information for each memory is assembled from the

different sensory systems and translated into whatever form necessary to be remembered. This is presumably the domain of the association cortices and perhaps other areas.

Consolidation-converting the encoded information into a form that can be permanently stored. The hippocampal and surrounding areas apparently accomplish this.

Storage-the actual deposition of the memories into the final resting places–this is though to be in association cortex.

Retrieval-memories are of little use if they cannot be read out for later use. Less is known about this process.

Encoding of memoryEncoding of memory It means classification and placing memory items in their proper

memory stores in brain Brain areas concerned with encoding of long term memory; 1. Hippocampus (major central role) all bits of information go to

it first 2. Amygdala (emotional memory) 3. Basal forebrain (Nucleus basalis or Meynerts nucleus) 4. Noecortex 5. Mammillary body of hypothalamus 6. Orbitofrontal cortex

Encoding of memoryEncoding of memory

Hippocampus store

Mamillary body

Orbitofrontalcortex

Basal forebrain Meynerts Nucleus

Amygdala store

(Temporal lobe)

Neocortex store

All bitsSelect important informations

(reward or punishment)

Cholinergic projections

Cholinergic projections

Cholinergic projections

Consolidation of memoryConsolidation of memory It means the process of conversion

of STM to LTM It takes from 5 min to 2 hrs It is interrupted by

1. Deep anaesthesia

2. Brain concussion

3. Electroconvulsive therapy

Brain Regions involved in Consolidation of Brain Regions involved in Consolidation of memorymemory

• Hippocampus• Anterior & lateral

temporal lobe,• Medial temporal lobe • Amygdala

Hippocampus and Consolidation of memoryHippocampus and Consolidation of memory

• The hippocampal region is critical for the consolidation of information in long-term memory

Evidence

• Three major excitatory neural components of the hippocampus

Perforant pathway• forms excitatory connections between the parahippocampal cortex

and the granule cells of the dentate gyrus

Mossy fibers

• connect the granule cells of the dentate gyrus to the CA3 pyramidal cells

Schaffer collaterals• connect the CA3 pyramidal cells to the CA1 pyramidal cells

Disorders of MemoryDisorders of Memory

1) Amnesia → loss or impairment of memoryIt may be;

a) Retrograde amnesia•It means inability to recall memories from the past

(retrograde: going backwards), that is from the long- term memory stores.

•Transient brain malfunction erase 1ry memory •It usually follows a traumatic event that interferes with the

normal activity of the brain, such as a strong brain concussion and vascular strokes

Disorders of MemoryDisorders of Memory

b)Anterograde amnesia• It is the inability to store new information in the long-term

memory for later recall. • It usually results from lesions of the medial portions of the

temporal lobe, a region that include the hippocampus, amygdala, and the adjacent areas of the temporal

c) psychogenic or hysterical amnesia• Rare

• Sudden loss of memory of all information• Exposure to severe psychological stress

Disorders of MemoryDisorders of Memory

2) Senile dementia and Alzheimer diseaseIt occurs in old age (senile dementia) and middle age

(Alzheimer), but it can occur at any age •It is characterized by impairment of memory, lack of

concentration, inattentiveness •Incidence: 10-15 % after age of 65 years

•Mechanism:•Loss of cholinergic terminals that diffuse from nucleus

basalis to neocortex, amygdala and hippocampus

THANKSTHANKSTHANKSTHANKS

Dr. Abdel Aziz Hussein, Mansoura Faculty of Medicine