Week 8 ELM 16: Learning and Memory I

Introduction to Memory

• Learning:
  • Acquisition of new knowledge or skills.
  • Adaptive.
• Memory:
  • Retention of learned information.
  • Linked to storage and retrieval.

Types of Memory

• Declarative (Explicit):
  • Facts.
  • Events.
• Non-Declarative (Implicit):
  • Procedural skills/habits.
  • Associative: Conditioning (e.g., salivation).

Brain Regions Involved in Memory

• Hippocampus: Explicit (declarative) memory.
• Cerebellum and Basal Ganglia: Procedural memory.
• Amygdala: Emotional responses.
• Cortex: Short- and long-term explicit memory.

Hippocampus and Navigation

• Place cells: Hippocampal neurons that fire when an animal is in a specific location (place field).
• Cognitive maps: Internal neural representation of the landscape.
• Taxi drivers:
  • London taxi drivers have more grey matter in the hippocampus compared to bus drivers.
  • Grey matter levels correlate with years of navigation experience.
  • Spatial knowledge is associated with hippocampal grey matter volume.

Formation of Memories

• Short-Term Memory:
  • Lasts seconds to hours.
  • Repetition promotes retention.
  • Limited capacity.
  • Labile (sensitive to disruption).
  • Does not require new RNA or protein synthesis.
• Long-Term Memory:
  • Lasts days to years.
  • Unlimited capacity.
  • Consolidated (insensitive to disruption).
  • Requires new RNA or protein synthesis.
• Consolidation: Process of stabilizing a memory trace after its initial acquisition.
• Working Memory: Holds information "in mind."

Stages of Memory

• Encoding: Brain receives information (sensory stimulus).
• Storage: Brain retains information.
• Retrieval: Brain retrieves and utilizes information.

Basic Mechanisms of Memory

• Learning and memory involve changes in existing neural circuits.
• Changes include altered synaptic strength and neuronal excitability.
• Intracellular signaling pathways play a key role.

Activity-Dependent Synaptic Plasticity (Hebbian Plasticity)

• "Neurons that fire together, wire together." (Hebb, 1949)
• A’s efficiency in firing B increases when axon of cell A excites cell B repeatedly.

Long-Term Potentiation (LTP)

• Persistent strengthening of synapses following high-frequency stimulation.
• Produces a long-lasting increase in signal transmission between two neurons.
• Mechanism of synaptic plasticity.
• Principal model of mechanisms underlying learning and memory.

Diagram of a Synapse

• Dendrites contain spines for synaptic contacts.
• Axon terminal releases neurotransmitters.
• Synaptic cleft is the space between neurons.
• Postsynaptic density has receptors.

Glutamate Receptors

• AMPA receptor:
  • Requires glutamate to open, allows Na^+ influx.
• NMDA receptor:
  • Requires glutamate + glycine + depolarization to open, allows Na^+ and Ca^{2+} influx.

LTP Mechanisms

• AMPA and NMDA receptors involved.
• Presynaptic changes:
  • Increased neurotransmitter vesicles.
  • Increased neurotransmitter release.
• Postsynaptic changes:
  • Increased dendritic area and spines (increased sensitivity).
  • Increased AMPA receptors.

Postsynaptic Mechanisms

• Diverse signaling pathways involved.
• PKA plays an important role.
• Different pathways converge on common targets (e.g., ERK).
• Requires protein synthesis.
• ERK = Extracellular signal-regulated protein kinases

Long-Term Potentiation and Morphological Changes

• Changes in size of dendritic spines.
• Increase in the number of neurotransmitter receptors.
• Increase in presynaptic vesicles.
• Increase in postsynaptic ribosomes.
• Changes in calcium compartmentalization.
• Increase in independent synaptic release sites.
• Increase in transmission.

Long-Term Depression (LTD)

• Synaptic transmission occurring with weak postsynaptic neuron depolarization causes LTD.
• LTD expressed by a long-lasting decrease in the efficiency of synaptic transmission.
• A rise in postsynaptic Ca^{2+} can trigger both LTP and LTD.
  • Strong depolarization leads to high levels of Ca^{2+} (LTP).
  • Weak depolarization leads to little Ca^{2+} influx (LTD).

Physiological Functions of LTD

• Hippocampus-dependent learning and memory.
• Fear conditioning in amygdala.
• Recognition memory in perirhinal cortex.
• Cerebellar learning.

Pathological States Involving LTD

• Psychiatric disorders (e.g., depression, schizophrenia).
• Drug addiction.
• Mental retardation (fragile X syndrome).
• Neurodegenerative diseases (e.g., Alzheimer's disease).

Memory Problems

Amnesia

• Loss of memories.
• Often result from trauma.
• Can be transient or permanent.
• Anterograde amnesia: difficulty learning new information.
• Retrograde amnesia: difficulty remembering past information.

Patient HM

• The most studied individual in neuroscience.
• Bilateral medial temporal lobe resection led to anterograde amnesia.
• Could not remember anything after the operation, but memory before surgery was intact.
• Case helped discriminate between short- vs. long-term memory and declarative vs. non-declarative memory.

Dementia

• Group of symptoms affecting memory, thinking, and social abilities.
• Different causes; Alzheimer’s disease is most common.
• More than 850,000 people in the UK diagnosed with dementia.
• Progressive; symptoms get worse with time.
• Health and social care costs around £26.3bn per year.

Different Causes of Dementia

• Affect different parts of the brain, leading to different symptoms.

Alzheimer’s Disease (AD)

• Accounts for >80% of total dementia cases in the elderly.
• One new case diagnosed every 3.2 minutes in England and Wales.
• Characterized by intracellular neurofibrillary tangles and extracellular Beta-amyloid plaques.
• Memory loss is the key symptom, with continuous decline in thinking, behavioral, and social skills.
• No cure currently.

Vascular Dementia (VD)

• Second most common cause of dementia.
• Can develop after a stroke or from conditions damaging blood vessels (e.g., atherosclerosis, high blood pressure, or diabetes).
• Symptoms vary, affecting memory, reasoning, planning, or judgment.
• Treatment focuses on managing contributing health conditions and risk factors.

Summary

• Different types of memory are stored in different brain areas.
• Learning and memory involve changes in existing neural pathways.
• Synaptic strength is altered following experience: activity-dependent synaptic plasticity.
• LTP and LTD are different types of synaptic plasticity and are key for learning and memory.