Physiology of Memory and Learning Abdel Aziz Mohamed

Physiology of Memory and Learning Abdel Aziz Mohamed Hussein lecturer of physiology Mansoura faculty of medicine Member of American Society of Physiology

Memory an Learning l Learning and memory are higher-level functions of the nervous system. l Learning is the neural mechanism by which a person changes his or her behavior as a result of experiences. l Memory is the mechanism for storing what is learned.

Learning l♦ Def l It is the ability of previous experiences to modify the inborn reactions or create new ones l It or is the acquisition of knowledge or skills as a result of experiences and consequently it can alter behavior on basis of this experiences l Learning is the process by which we acquire knowledge about the world (Eric Kandel, 2000) l Learning refers to a more or less permanent change in behavior which occurs as a result of practice

Learning l Types 1. Associative 2. Non-associative (Relation of one stimulus to another) (ignore or react ) a. Classic conditioning a. Habituation b. Operant conditioning b. Sensitization

l In Associative Learning this type of learning, the subject learns about the relationship that can associate one stimulus to another l It is a conditioned process which results in the formation of learned responses called conditioned reflexes l 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)

l This a) Classic Conditioning type of conditioned reflexes was 1 st described by Pavlov (Russian Physiologist) l He noticed that his experimental dogs salivate just on seeing the animal house keeper who used to feed l 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 Conditioning

a) Classic Conditioning l This type of conditioning can be integrated a different levels of CNS l Requirements: l 1) CS applied before US l 2) Pairing must occur several times l 3) No separation between the CS and US

a) Classic Conditioning

b) Operant Conditioning l In 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 l Alerting signal acts as conditioned stimulus whereas pleasant or unpleasant event that follow performance of learned response represents unconditioned stimulus

b) Operant Conditioning

b) Operant Conditioning Example: l Car driver and traffic light l The car driver stops the car on seeing the red traffic light and drives on seeing the green light Integration: l Hippocampus and amygdala are important in linking the stimulus to the operation l Integration occurs in CC especially orbitofrontal cortex

l In Non-associative Learning this type of learning, the subject learns whether to ignore or react to a certain stimulus l It is a simple way of learning that does not need association between 2 stimuli l It is 2 types; l A) Habituation l B) Sensitization

l It Habituation is a gradual decrease in the response to stimulus when it is frequently repeated l It is simple and widespread l Examples: l A loud and unexpected sound produces looking towards the source of sound, change in heart rate, and change in blood pressure l If the sound turns to be insignificant, its repetition results in little or no response

Habituation l It is a stimulus specific e. g. traffic noise and mother and baby l Mechanism: l Repetition of the stimulus close Ca channels in presynaptic neurons →↓ Ca influx →↓ release of neurotransmitters →↓ behavioral responses to the stimulus

Habituation l Experiments performed in Aplysia californica

l It Sensitization is a potentiation in the response to stimulus (painful or pleasant) when it is frequently repeated l It is simple and widespread l Examples: l 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 l Stimulus specific: l One who is bitten by dogs will not be afraid of donkeys or cows

Sensitization l Mechanism: l Strong or noxious stimulus → facilitating interneurons (serotonin) →↑ c. AMP 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

Sensitization

Sensitization

Memory l Def memory is the process by which that knowledge of the world is encoded, stored, and later retrieved (Kandel (2000), l Memory is a phase of learning l l 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

Memory l Def l It is the ability of the brain to store information and recall it at later time or l Capacity of the brain: It is limited (total capacity of brain is 3 x 108 bits) l So, informations entering brain are either; l Selected and stored (1%) → most important B. Other (99%) → are neglected and forgotten A.

Memory l Information l l l l 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

l Classification Memory of memory:

1. Sensory 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 • Vision: iconic memory 2. Hearing: echoic memory 1. Mechanism: • 1. Stimulation of reverberating circuits → repeated activation of neurons • 2. Synaptic sensitization if sensory experience coupled with painful stimuli •

1. Sensory 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 Memory l Duration: (min to hours) l Capacity – Small bits of informations – Miller’s magical number: 7± 2 chunks of information l Entry into storage: verbalization (describing the items in words) l Recall or access to storage: rapid l Mechanism: l Made by formation of temporary memory traces

2. Short-term Memory l l l l 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 Memory l Duration: (hours to years ) l Capacity – Very large – Information stored according to its significance l Entry into storage: practice or and punishment or reward l Recall or access to storage: slow l Mechanism: l Made by formation of memory engrams (longlasting memory traces) formed by structural changes in presynaptic terminals

Long-term potentiation l l l 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 Ca 2+ to enter. 3. The entry of Ca 2+ into the postsynaptic neuron causes long-term potentiation in that neuron. 4. The entry of Ca 2+ 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 Memory l Mechanism: l memory engrams made up by; l 1. increase in number of vesicles l 2. increase in number of presynaptic terminals l 3. increase in release sites of chemical transmitters l 4. generation of new receptor sites l 5. long term potentiation l Engrams remain for long time up to several years l Formation of new engrams requires protein synthesis

3. Long-term Memory l Mechanism of forgetting: 1. Proactive inhibition by previously stored materials (more common) 2. Retroactive inhibition by subsequently stored material

4. Permanent Memory l Duration: (permanent) l Capacity – Very large l Entry into storage: very frequent practice l Recall or access to storage: very rapid (recall not affected by brain injury (like name, write, and read) l Mechanism: l Advanced stage of long-term(permanent engrams) l Mechanism of forgetting : l No forgetting

Phases 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. l Consolidation-converting the encoded information into a form that can be permanently stored. The hippocampal and surrounding areas apparently accomplish this. l Storage-the actual deposition of the memories into the final resting places–this is though to be in association cortex. l Retrieval-memories are of little use if they cannot be read out for later use. Less is known about this process. l l

Encoding of memory l l l l 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 memory Select important informations (reward or punishment) All bits Hippocampus store Amygdala store (Temporal lobe) Mamillary body Cholinergic projections Basal forebrain Meynerts Nucleus Neocortex store Orbitofrontal cortex

Consolidation of memory l l l 1. 2. 3. It means the process of conversion of STM to LTM It takes from 5 min to 2 hrs It is interrupted by Deep anaesthesia Brain concussion Electroconvulsive therapy

Brain Regions involved in Consolidation of memory • Hippocampus • Anterior & lateral temporal lobe, • Medial temporal lobe • Amygdala

Hippocampus 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 CA 3 pyramidal cells Schaffer collaterals • connect the CA 3 pyramidal cells to the CA 1 pyramidal cells

Disorders of Memory 1) Amnesia → loss or impairment of memory l It 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 1 ry 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 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 l • • • c) psychogenic or hysterical amnesia Rare Sudden loss of memory of all information Exposure to severe psychological stress

Disorders of Memory 2) Senile dementia and Alzheimer disease l It 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

S K N A H T Dr. Abdel Aziz Hussein, Mansoura Faculty of Medicine