Neurobiology of Memory

Dr Parth GoyalDr Priyal Desai

Important Definitions• Learning: A process by which new information is acquired by

the nervous system and is observable through changes in behaviour

• Memory: Refers to the encoding, storage and retrieval of learned information

• Synaptic Plasticity: The ability of the synapses to strengthen or weaken over time.

• Strengthening of synapses over time is known as Long Term Potentiation (LTP)

• Weakening of synapses over time is known as Long Term Depression (LTD)

Neuro-Plasticity • Synaptic connections between neurons

provide a basic wiring of the brains circuitry.

• This connectivity between neurons is dynamic and is constantly changing in response to neural activity and other influences.

• Synaptic Plasticity is of 2 forms: Short term and Long term.

Long term Plasticity • Two forms: LTP and LTD

• Long term Potentiation: It is a candidate for long term memory function in mammalian brains.

• Occurs when a post synaptic neuron is “Persistently Depolarised" after a “High Frequency” burst from pre synaptic neuron.

Features of LTP• Established quickly and lasts for a long

time (days to years)

• Associative in nature; occurs only at “Potentiated synapses”, terminating at the post synaptic cells

• Occurs prominently at the hippocampus; structure that is pivotal to memory formation.

Associativity and Specificity at Synapses

State of NMDA Receptors at Rest and while being Depolarized

Mechanism of LTP

• http://sites.sinauer.com/neuroscience5e/animations08.02.html

Long Term Depression

• If synapses would simply increase in strength due to LTP, eventually it would be difficult to encode new information

• Thus it is necessary to selectively weaken specific set of synapses.

• LTD occurs when schaffer collaterals are stimulated at 1 Hz for long periods.

• LTD can erase the increase in EPSP size due to LTP.

LTD In Hippocampu

s

LTD in Cerebellum

Types of Memory• There are 2 main types of “Qualitative”

memory systems:

• a) Declarative: Storage and retrieval of material that is available to the consciousness and can be expressed in language.

• b) Non Declarative: Also k/a “Procedural Memory”, something that is not available to the consciousness. It involves “skills and associations”.

Categories of Memory

Temporal Memory Systems

• Memory can also be classified on the basis of the “time” over which it is effective

• a) Immediate Memory

• b) Working Memory

• c) Long Term Memory

Temporal Categories of Memory

Memory Consolidation

• The way by which immediate and short term memories are encoded into long term memories is known as memory consolidation.

• Steps involved in memory consolidation:

• 1) The event is experienced and encoded by a virtue of the cortical regions involved.

• 2) At the same time, the Hippocampus and the adjacent cortices receive pertinent information

• 3) Later when the original event is recalled, the same set of cortical regions get activated.

Contd..• In case a subset of a cortical region is activated, the hippocampus and

the other structures can facilitate recall by activating the remaining cortical region. This is known as “Pattern Completion”.

• If on retrieving the original event, it becomes associated with new information, the Hippocampal-Cortical networks can be modified accordingly.

• In this way a gradual consolidation process occurs which can change the nature of memory storage.

• The neo-cortical components over a period of time and on repeated recall can become so efficiently linked, that the original event can be recalled without any help from the hippocampus and the associated structures.

• Areas in the Frontal Lobe and the Temporal lobe are important in facilitating this long term recall of information.

Techniques used in Consolidation of Memory

• Some of the most commonly used methods are

• a) Priming

• b) Associative Learning

• C) Conditioned Learning.

Priming• It is defined as: “ A change in the processing of a

stimulus due to a previous encounter with the same or a related stimulus with or without conscious awareness of the original encounter.

• However the information stored in priming is not particularly reliable.

• Priming is resistant to brain injury, aging and dementia.

• Priming shows that previously presented information always influences our subsequent behaviour.

Priming Test

Fallibility of Human Memory

Associative Learning • Normal human capacity to remember a string of numbers is

limited to max 7-9 numbers.

• However some people are able to remember larger strings, by employing other techniques that enhance memory.

• By “associating” the object in question with some meaningful form of information, memory can be enhanced significantly.

• The capacity of memory depends very much on

• a) what the information means to the individual

• b) how it can be associated with the information already stored.

• Motivation also plays an important role in memory formations.

Role of Past experience, Context and Relevance in Memory

Motivation in Memory

Conditioned Learning • It is a category of non declarative memory that has

been most extensively studied in the past.

• It is defined as: “Generation of novel responses that is gradually elicited by repeatedly pairing a novel stimulus with a stimulus that normally elicits the response being studied”

• Two main types:

• a) Classical Conditioning

• b) Operant conditioning

Conditioned Learning

• Conditioned Response

• Unconditioned Stimulus

• Conditioned Stimulus

• Unconditioned Response.

Operant Learning

• It refers to altered probability of a behavioural response engendered by associating the response with a reward or punishment.

Sleep and Memory• Memory storage appears to be specifically

aided during deep sleep within a few hours after learning (mostly prominent in stage 3 & 4, SWS)

• Some data indicates that the SWS facilitates the storage of declarative memories and not non declarative ones

Forgetting • Initially it was believed that everything that is learnt is

stored in the brain, although sometimes particular details are not accessible.

• However this hypothesis has been proved wrong.

• People tend to gradually forget what they have stored in long term memory, thus giving us more proof that our memory is unreliable at best.

• Memories that are unused, unrehearsed and have not particular importance deteriorate over time.

• Forgetting unimportant information is a crucial ability for leading a normal life.

Brain systems involved in storage of Declarative

Memory• Learning about the various structures of the brain

involved in storage of declarative memories is a challenge

• Much of the information is based on studies from individuals who have sustained brain injuries.

• Taken together, these cases implicate the role of

• a) Midline diencephalic structures (Thalamus, Hypothalamus)

• b) Medial temporal lobe structures (Hippocampus, Peri-rhinal, Enterorhinal cortex and Para hippocampal region)

Contd..• The studies discussed subsequently

suggest that primates and other mammals depend on medial temporal structures, to encode and consolidate memories of events and objects in time and space,

• Just as humans use these same brain regions for the initial encoding and consolidation of declarative memories.

Contd. • Studies (PET and fMRI) have shown that the neurons in

the hippocampus and para hippocampal cortex are selectively recruited by tasks that involve declarative memory formation.

• Studies have shown that the posterior hippocampus appears to be particularly useful in remembering spatial information. This is exhibited in the case of London Taxi Drivers.

• Confirming the role of experience in performance the size of the posterior hippocampus in cab drivers scales positively with the number of months spent driving a cab.

Contd..• Neuronal activation within the

hippocampus and the allied cortical areas of the medial temporal lobe largely determine the “transfer of declarative information into long term memory”

• and that the robustness with which such memories are encoded, depends on structural and functional changes, that occur as a result of experience.

Structures involved in Storage of Declarative Memory

Role of Hippocampus in Memory

Long term Storage of Declarative Memories

• We have seen that the immediate storage of declarative memories occurs in the structures of the medial temporal lobe

• However when these structures are damaged, due to injury or illness, the patient “does not” forget the memories that he acquired earlier in life

• This implicates the involvement of other regions of the cortex in the long term storage of declarative memories

Lines of Evidence• There are multiple evidences that are available

to prove the following:

• a) Lashley’s “Mass action principle”, which states that any degradation in learning and memory depends on the amount of cortex destroyed; the more complex the learning task the more disruptive the lesion should be.

• b) Patients undergoing ECT, usually show impairments in retrograde memories ranging from a few hours to days.

Contd..• c) Patients with damage to the regions of

association cortex e.g the association cortex of the inferior temporal lobe is involved in linking images (faces/objects) with meanings. Damage to this region affects the ability of the person to recognise the objects, indicating that memory is also stored in this region.

• d) Neuro-imaging Evidence: when subjects were asked to recall words associated with images, cortical areas got activated on recall.

Hippocampus and possible declarative memory storage sites.

fMRI Studies to locate memory sites.

Frontal Lobe and its Contributions

• Role of Frontal Lobe: The association cortices located particularly in the frontal lobe are associated with retrieval of memories.

• The dorsolateral and anterolateral aspects of Frontal lobe are activated when declarative memories from long term storage are retrieved.

• Patients with damage to these areas fail to recall these memories accurately and often resort to confabulation.

Brain Systems involved in Non-Declarative Memory acquisition and

storage.• Non declarative memories involve the:

• a) Basal Ganglia

• b) Prefrontal Cortex

• c) Amygdala

• d) Sensory association cortices

• e) Cerebellum

• They don’t involve the midline temporal lobe structures.

Lines of Evidence• Ischemic damage to the cerebellum

produces profound deficits in classical eye-blink conditioning but does not interfere with formation of new declarative memories.

• Lesions in visual association cortex produce profound impairment in visual priming but leave declarative memory intact.

Contd.. • The basal ganglia and the prefrontal cortex are profoundly

important in non declarative memory recall.

• Evidence: Patients with huntington’s perform poorly on motor skill learning tests, such as manually tracking a spot of light, tracing curves using a mirror or reproducing the sequence of finger movements.

• Patients with Parkinson’s as well as Prefrontal lesions caused by strokes or tutors, show similar deficits on these tasks.

• Neuroimaging studies have corroborated these findings. Normal individuals show activation of these brain regions while performing these tasks.

Summary of Storage Sites

Disorders of Memory• Memory disorders can be classified into 2

main types:

• a) Physiological: Infantile Amnesia

• b) Pathological: Amnesia’s (Retrograde or Anterograde)

• Amnesia’s most commonly occur due to brain injuries, but some can also be Psychogenic in origin.

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Infantile Amnesia• The absence of conscious memories fro the first 3 years of

life is known as Infantile Amnesia

• Traditional Views: Regression and Retrieval Failure.

• Present View: Declarative memories do not become fully available by the age of 3 years, whereas non declarative emerges early in infancy.

• Thus currently it is considered as a “failure of storage” rather than failure of retrieval.

• The amnesia in this period is linked with the under development of the neocortex, rather than that of the medial temporal structures.

Psychogenic Amnesia

• Memory problems arising due to psychological factors is known as “psychogenic amnesia”

• It is important to differentiate psychological and organic amnesia in a patient. Some of the points of difference are:

Sr.No Features Psy Amnesia Organic

Conditions

1 New Learning Capacity Intact Impaired

2 Retrograde Amnesia

Severe(autobiographical recall impaired)

Autobiographical memory is intact

3Formal

Neuropsychological Tests

Results variable Results in sync with the deficits

4 CourseVariable (Can persist or can

resolve)Usually

persistent.

Psychological Amnesia V/S Malingering

• Features in favour of genuine psychological amnesia:

• 1) Tests scores are not as low as possible, nerver worse than chance level

• 2) Memory access is improved by Amytal Interviews

• 3) Significant premorbid psychiatric history.

Example of Psychogenic Amnesia

Retrograde and Anterograde Amnesia’s.

• Inability to recall previously learned information is known as Retrograde Amnesia

• Inability to learn new information across all sensory modalities and stimulus domains is known as Anterograde Amnesia

• Ribot’s Law: Deficits are most severe for information that was most recently learned.

Case of H.M.• Condition: intractable temporal lobe epilepsy. Got operated

for a bilateral temporal lobectomy.

• Structures removed: Hippocampus, Parahippocampus corticies, Enterorhinal corticies, Piriform cortices, Amygdala.

• Pattern of memory deficits: Severe anterograde amnesia, with impairments in explicit memory. b) Problems of committing new events to his explicit memory c) impaired new semantic knowledge d) moderate retrograde amnesia, upto 11 years

• Intact Domains: Intact working and procedural memory. b) Intact motor learning skills c) Autobiographical memory recall

Case of K.C.• Injury: Due to fall from motor cycle.

• Structure involved: Medial temporal lobe along with complete B/L Hippocampus.

• Type of Amnesia: a) Severe anterograde with temporally graded retrograde amnesia, which covers his whole life b) Retrograde episodic memory c) Loss of emotional details from past memories d) Loss of autonoetic consciousness (unable to envision himself in the future)

• Intact Domains: Priming was intact. b) Semantic Memory was intact

Case of N.A.• Injury: Resulted from a mock duel from another

service man. Miniature fencing foil entered the right nostril and then punctured the base of the brain.

• Structures involved: L-Thalamus, Posterior Hypothalamus, Mamillary nuclei, Rt anterior temporal lobe with amygldaloid complex.

• Patterns of amnesia: Severe anterograde amnesia for declarative memory, more verbal than spatial. Fails badly on formal tests of new learning ability. Deficits in semantic memory seen.

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