Learning + Memory

Learning and Memory

Overview

  • Learning is: The process of acquiring new information.

  • Memory is: The ability to store and retrieve information.

Historical Context

  • Oracle of Trophonius

  • Spring of Mnemosyne

  • Spring of Lethe

Memory Organization in the Brain

Karl Lashley, 1930s

  • Proposed the Law of mass action: The severity of memory impairment correlates with the size of the cortical lesion.

Key Researchers

  • William B Scoville

  • Brenda Milner

  • Research from Scoville and Milner, 1957.

The Case of Patient H.M.

Patient Profile

  • Name: Henry Molaison (H.M.)

  • Underwent bilateral temporal surgery in 1953 at age 27 to treat epilepsy.

  • Died in 2008 at age 82 without forming new conscious memories.

  • Resulted in Anterograde amnesia.

  • Ablated areas: hippocampus, parahippocampal gyrus, and amygdala.

Findings from H.M.'s Case

  • Severe (complete) deficits in acquiring new declarative memory:
      - Episodic memory (personal/autobiographical knowledge)
      - Semantic memory (facts/knowledge)

  • Old declarative memory (events before surgery) remained intact.

  • Non-declarative (implicit) memory largely intact:
      - Improved performance on motor tasks without conscious recollection of prior performance.

Testing Hippocampal Function in Animals

Morris Water Maze

  • A behavioral test to assess spatial memory in animals:
      - Demonstrates that the hippocampus is crucial for encoding and consolidating memories.

Types of Memory

Memory Storage Duration

  • Sensory Register:
      - Vision: 1 second
      - Auditory: 5 seconds

  • Short-term Memory:
      - Duration: 30 seconds
      - Capacity: 7 ± 2 items before displacement

  • Long-term Memory:
      - Involves synaptic modifications, timelessness, rehearsal-consolidation, and retrieval.

Working Model for Memory

  • Components:
      - Visual
      - Auditory
      - Motor
      - Olfactory
      - Gustatory

  • Central Executive Functions: Oversee and integrate various types of memory.

Two Main Types of Memory

  • Declarative Memory (conscious):
      - Episodic: Daily episodes, personal experiences.
      - Semantic: Facts and meanings.

  • Non-declarative Memory (generally not conscious):
      - Skills (motor skills)
      - Priming (associations)
      - Conditioning (associative learning)

The Case of Patient K.C.

Patient Profile

  • Lesions due to a motorcycle accident at age 30.

  • Normal intellectual abilities but suffered severe deficits in:
      - Anterograde and retrograde episodic memory (unable to form new memories or remember personal life events).

  • Largely intact:
      - Semantic memory (acquisition of some new knowledge).

Detailed Memory Types

Declarative Memory

  • Can be verbally expressed:
      - Episodic: Remembering personal events (e.g., first day of school).
      - Semantic: Knowing factual information (e.g., capital of France).

Non-declarative (Procedural) Memory

  • Skills: Performance through practice (e.g., riding a bicycle).

  • Priming: Enhanced ability to recall information.

  • Conditioning: Emotional responses to stimuli.

Non-declarative (Implicit) Memory: Priming

Experiment Overview

  • Test Conditions:
      - Recall after exposure to List A vs. List B.
      - Completion rates of word stems showed priming effects when List A items were presented previously.

  • Priming completion rates observed for various words.

Learning through Conditioning

Classical Conditioning (Pavlov)

  • Involves associating a neutral stimulus with a reflexive response.
      - Example: Pavlov's dogs drooled at the sound of a bell associated with food.

Instrumental (Operant) Conditioning

  • Behavior is modified by consequences (reinforcements and punishments).
      - Reinforcement increases behavior frequency.
      - Punishment decreases behavior frequency.
      - Extinction occurs without reinforcement.

  • Skinner Box interpretation of behavior conditioning.

The Role of Previous Knowledge and Motivation

  • Examples:
      - Hungry subjects performed better on recognition tests involving food-related items, reflecting motivated memory.

  • Recognition influenced by preconceived knowledge and current state.

Areas Involved in Implicit Memory

  • Explicit (conscious) Memory
      - Types:
        - Episodic: Personal experiences
        - Semantic: Factual knowledge

  • Implicit (unconscious) Memory
      - Types:
        - Skills: Motor habits
        - Emotional responses

  • Neural Correlates:
      - Basal ganglia, premotor cortex, thalamus, amygdala, substantia nigra, cerebellum.

Areas Involved in Declarative Memory

  • Significant brain structures:
      - Prefrontal cortex, basal forebrain, mammillary bodies, fornix, thalamus, cingulate gyrus, hippocampus, CA regions (1-4), and associated pathways.

Consolidation of Memory

  • Detailed structural organization showing how neocortical areas intersect with the hippocampal region to consolidate memories.

Types of Amnesia

Definitions

  • Anterograde Amnesia: Inability to form new memories.

  • Retrograde Amnesia: Loss of old memories.

Mechanisms Underlying Memory

Synaptic Plasticity

  • Involves changes at synapses through dendritic spines reconstruction.

Long-term Potentiation (LTP)

  • Key features:
      - Rapid triggering
      - New protein synthesis requirement
      - Lasts for months

  • Fit as a candidate for cellular mechanisms of learning
      - Hebb's principle: "Cells that fire together, wire together."

Experimental Observations on LTP

Bliss and Lømo, 1973

  • Demonstrated LTP in hippocampal CA3 to CA1 connections through high-frequency stimulation.

  • Measurement of EPSP membrane potential changes associated with LTP.

Molecular Mechanisms of LTP

Factors Involved

  • Calcium ions (Ca2+Ca^{2+}) role in activating NMDA and AMPA receptors at the synapse.

  • Key molecules involved:
      - Calmodulin, Protein kinases, Transcriptional regulators, e.g., CREB.

Aging and Its Effects on Memory

Factors Affecting Memory

  • Age-related changes in brain structure:
      - Loss of grey and white matter
      - Changes in neurovascular function
      - Impact of neurotransmitter levels

  • Other contributing factors:
      - Education, life experience, stress, genetics, exercise, diet.

Memory Decline with Aging

  • Notable decrease in brain volume mostly due to loss of synapses rather than neurons.

  • Decline in executive functions impacting tasks related to attention and memory.

  • Stress-induced oxidative damages and dopamine loss contributing to memory impairments.

Alzheimer's Disease

Overview

  • Most common form of dementia, accounting for 60-80% of cases.

  • Statistics:
      - Affects 5-10% of individuals over 65 years old and up to 45% over 85 years old.

  • Symptoms include loss of recent memory, attention, language skills, spatial orientation, abstract thinking, personality changes, and motor control deficits.

Pathological Hallmarks of Alzheimer's

  1. Amyloid Plaques: Accumulation of beta-amyloid peptides; mutations in presenilin genes increase risk.

  2. Neurofibrillary Tangles: Aggregates of hyperphosphorylated tau proteins which stabilize microtubules.

  3. Diffuse Neuronal Loss: Associated with synaptic dysfunctions and neurodegeneration.