Learning and memory (Courteney Fisher)

Describe what happened to patient H.M

• has tissue removed from temporal lobes (hippocampus)

• short-term memory intact

• he was unable to remember events that happened several years before the surgery

• unable to form new memories

• unable to learn to navigate a new neighbourhood

• short-term memory stayed intact

• older memories are more preserved

Describe how patient H.M did in the mirror tracing task

• traced a star while only looking at his hand in a mirror

• despite having no conscious memory of practicing, his performance improved over time

What did the results from the mirror tracing task that patient H.M did show

showed that procedural memory was intact, even though declarative memory was impaired

• procedural memory relies on the basal ganglia and cerebellum, which was unaffected by H.M’s surgery

• this distinction is often summarised at “knowing that” vs. "knowing how” and underpins modern memory research

What is procedural memory

skills like riding a bike or playing an instrument

What is declarative memory

facts, names, dates

What happened to H.M’s brain during surgery

• removed large portions of both medial temporal lobes

  • most hippocampus, entorhinal, perirhinal, parahippocampus cortices, and part of the amygdala

• some posterior hippocampus and other areas remained

• cerebellum was unaffected

What does H.M’s memory show

that different memory types rely on different brain systems

• hippocampus and surrounding cortex are critical for a new declarative memory

What happened to patient N.A.

• became amnesic after an accident where a miniature fencing foil injured his brain through entering his nostril and damaged his dorsomedial

• his accident happen in 1960, he had almost normal recall of events in the 40s and 50s

What is Korsakoff’s syndrome

• causes memory loss and confabulation (making up events)

• the damage is mostly irreversible

How does Korsakoff’s syndrome occur

• mainly due to thiamine (vitamin B1) deficiency

  • often from alcoholism or malnutrition

• mammillary bodies shrink, with additional damage in the dorsomedial thalamus and sometimes frontal lobes

• in malnourished populations, sudden high-glucose intake can trigger similar brain damage

Two main divisions of long-term memory

• declarative memory (conscious)

• non-declarative (unconscious)

Types of declarative memory (conscious)

• episodic: personal experiences

  • e.g. your last birthday

• semantic: factual knowledge

  • e.g. Paris is the capital of France

Types of non-declarative memory (unconscious)

• procedural: skills and habits

  • e.g. riding a bike

• priming: exposure to one stimulus influences response to another

• classical conditioning: associating one stimulus with another

• habituation/sensitisation: simple reflexive learning

What do different memory types rely on

distinct brain circuits and mechanisms

What is memory

can be defined as an experience-dependent alteration in behaviour that persists beyond the environmental stimuli that produced it

• memory is a lasting change in behaviour caused by past experiences

  • it allows experiences to leave a lasting mark on the brain

Memory is a multi-stage process with four key steps:

1. encoding: taking in new information

• e.g. adding a book to a library catalogue

2. consolidation: stabilising and storing information

• e.g. shelving the book

3. retrieval: finding and using the stored information when needed

4. forgetting: when information fades or is lost

• e.g. a missing or overwritten book

What is an engram

the physical basis of a memory, represented by a network of neurones activated by a specific experience

What happens during encoding

certain neurones become active as the experience occurs

What happens during consolidation

these neurones stabilise their activity to store the memory

What happens during retrieval

the same neurones are reactivated, producing recall

What happens to memory after each recall

each recall temporarily destabilises the memory, which must then be reconsolidated

Where are memories stored (think of neurones)

in synaptic connections between neurones as coordinated patterns of activity, not in individual cells

An engram should satisfy four core criteria

• persistance

  • an engram is a persistent change in the brain, resulting from a specific experience

• ecphory

  • an engram is subjected to ecphory, meaning that an engram can be behaviourally reactivated

• content

  • an engram is content-specific to faithfully recall what has been encoded

• dormancy

  • an engram may exist in a formant state during the offline period between encoding and retrieval

Neurones are selectively recruited into memory engrams based on

their intrinsic cellular excitability

What type of cells are more likely to participate in memory encoding

cells with higher excitability, those with greater protein synthesis and metabolic readiness

During learning what happens to the synaptic strength

it increases among co-activated neurones, producing a distinct circuit that represents the memory trace

What minimises overlap between memories

the enormous number of neurones and synapses in the brain

What is the Hebbian theory

it is the principle that neurones that fire together, wire together, meaning the connection between two neurones strengthens when they are activated simultaneously

How can recently encoded memories be temporarily maintained

via learning-induced increased activity

What are recently encoded memories liable to

• easily altered (labile)

• highly susceptible to interference

• will rapidly decay without additional maintenance

What is required to transform a short-term, labile memory into one that persists long-term

gene expression and protein synthesis

What is long-term potentiation (LTP) defined as

a long-lasting strengthening of the synaptic response of a neurone following a brief high-frequency stimulation or similar induction protocol

Describe step 1 of long-term potentiation

• the presynaptic neurone releases glutamate into the synapse

• glutamate binds to AMPA receptors on the postsynaptic neurone, opening them and allowing Na⁺ ions to enter

• this depolarises the postsynaptic cell, which removes the Mg²⁺ block from NMDA receptors

• once unblocked, NMDA receptors are ready to let Ca²⁺ flow in during strong stimulation

• this sets the stage for LTP, the postsynaptic neurone is now ‘primed’ to strengthen the connection

Describe step 2 in long-term potentiation

• calcium (Ca²⁺) enters through the now-open NMDA receptors

• inside the postsynaptic neurone, Ca²⁺ triggers signalling cascades that lead to:

  • creation of new AMPA receptors

  • insertion of these receptors into the postsynaptic membrane

• with more AMPA receptors, the postsynaptic cell become more responsive to glutamate

• the same signal from the presynaptic neurone now produces a stronger response

Describe step 3 in long-term potentiation

• calcium inside the postsynaptic neurone activates nNOS, an enzyme that makes nitric oxide (NO)

• nitric oxide diffuse backwards across the synapse to the presynaptic neurone

• this retrograde signal tells the presynaptic neurone to release more glutamate in the future

• both neurones now work together - stronger release on one side, stronger response on the other

Describe step 4 in long-term potentiation

• dopamine marks important experiences, boosting long-term changes

• dopamine increases cAMP, which activated Protein Kinase A (PKA) → MAPK (mitogen-activated protein kinase) → CREB in the nucleus

• CREB turns on genes that make new proteins and structural components for the synapse

• this converts temporary strengthening into a long-term, stable memory through new protein synthesis and synaptic growth

Summary of long-term potentiation

• induction: when activity between two neurones tiggers the start of stronger communication

• maintenance: the connection is kept strong through chemical and structural changes

• expression: the strengthened connection makes it easier for the neurones to talk to each other in the future

Early studies showed that blocking NMDA receptors …

disrupts learning and memory

What did Morris et al., (1986)

• injecting APV (an NMDA blocker) into the hippocampus impaired spatial learning in animals

  • this proved the NMDA receptors are crucial for long-term potentiation, a key process for memory formation

  • blocking NMDA receptors prevents LTP, showing that LTP is a physiological basis for memory

  • these findings are important because many drugs target NMDA/glutamate pathways

What else does memory consolidation depend on

protein synthesis

What happened to the animals when tested later in Morris et al., (1986) study

• control animals show freezing behaviour, indicating memory retention

• in contrast, animals given the inhibitor fail to freeze, showing no memory of the conditioning event

• these findings demonstrate that new protein synthesis in the nucleus is essential for memory consolidation, enabling the stabilisation of synaptic changes

What happens if protein synthesis gets blocked

it prevents the formation of long-term memory, leaving only short-term which decays quickly

• this demonstrates that memory depends on structural changes in the brain, reflecting the creation of new synaptic components

• the evidence supports the concept of the engram - the physical representation of memory within neural circuits

What does memory retrieval involve

reactivation of the neurones that were originally recruited during learning

What happens if engram neurones are silenced

it selectively disrupts retrieval of that specific memory without affecting the ability to form new memories

How was patient S. memory like

exceptionally high memory capacity and retention, with virtually no forgetting

What happened to patient S. because of their virtually no forgetting

it led to functional impairments, including difficult filtering irrelevant information and recognising individuals after minor changes in appearance

From patient S. the case provides evidence that forgetting is a critical cognitive process that enables:

• generalisation of knowledge across contexts

• updating of memories to maintain accuracy with current experiences

• prevention of cognitive overload by discarding excessive or irrelevant details

What is forgetting

• an adaptive phenomenon

• can occur if the memory is no longer available

  • a storage deficit

  • complete engram degradation

What is the tendency of neural systems to degrade rather than to preserve information

natural

What are the multiple levels of analysis of an engram

• network (neighbourhood)

  • memories arise from coordinated activity across networks of neurones

• population (town square)

  • groups of neurones collectively encode a memory

  • no single neurone tells the whole story

• cellular (inside a house)

  • each neurone has thousands of synaptic connections integrating inputs

• synaptic (spark of connection)

  • synaptic plasticity strengthens or weakens connections to encode memory

• nuclear (city hall/memory HQ)

  • gene expression and protein synthesis consolidate long-term memories