Learning and Memory

Associative Learning

• Non-declarative memory involves associative learning.

• Classical (Pavlovian) conditioning: Learning through associating a neutral stimulus with significant events.

• Operant (instrumental) conditioning: Learning through associating behavior with significant events.

Classical Conditioning (Pavlovian Conditioning)

• Associative learning: Involves the association between two stimuli or between a stimulus and a response.

• Classical conditioning: A neutral stimulus, when paired with a stimulus that elicits a response, can elicit the same response when presented alone.

• Unconditioned Stimulus (US): Naturally evokes a response without training. The response is the Unconditioned Response (UR).

• Conditional Stimulus (CS): Does not naturally evoke the response but does after training. The learned response to the CS is the Conditioned Response (CR).

• Timing: CS and US must be presented simultaneously, or CS must precede US for conditioning to occur.

• Exceptions: Aversion

• Requires intact circuits in the cerebellum.

Pavlov's Experiments

• Before conditioning:

  • US leads to UR

  • Neutral Stimulus (NS) yields no conditioned response

• During conditioning: NS paired with US leads to UR

• After conditioning: CS leads to CR

Stimulus vs. Response: A conditioned response is elicited by the conditioned stimulus after the association is established, demonstrating the learned connection.

• Stimulus: What is sensed.

• Response: Behavior or physiological change.

Fear Conditioning and PTSD

• Fear conditioning is related to Post Traumatic Stress Disorder (PTSD).

Operant Conditioning

• Instrumental/Operant conditioning: Association between behavior and its consequences.

• Reinforcers:

  • Increase the frequency of preceding behavior.

  • Positive reinforcement: Introduction of an event or activity that increases behavior frequency.

  • Negative reinforcement: Removal of an event or activity that increases behavior frequency.

• Punishers:

  • Decrease the frequency of preceding behavior.

  • Positive punishment: Introduction of an event or activity that decreases behavior frequency.

  • Negative punishment: Removal of an event or activity that decreases behavior frequency.

Examples of Operant Conditioning

• Positive reinforcement

• Negative reinforcement

• Positive punishment

• Negative punishment

Hippocampal Spatial Neurons

• Place cells: Neurons in the hippocampus fire when an animal is in a specific location.

Memory consolidation during sleep:

• The correlation of cell activity during sleep is similar to activity during food searches when previously awake.

• $Wilson \ and \ McNaughton, 1994$

Three Processes of the Memory System

• Encoding: Sensory information goes to short-term memory.

• Consolidation: Information is consolidated into long-term storage.

• Retrieval: Stored information is retrieved.

• Reconsolidation: Return of a memory trace to stable, long-term storage after recall.

Stages of Memory

• Retrieving information from Long-Term Memory (LTM) can cause memories to become unstable and susceptible to disruption or alteration.

Memory Systems

• Long-term memory

  • Declarative (explicit):

    • Episodic: Medial temporal lobe, neocortex

    • Semantic: Medial temporal lobe, neocortex

  • Nondeclarative (implicit):

    • Skill learning (procedural): Striatum, motor cortex, cerebellum

    • Priming: Neocortex

    • Classical conditioning: Amygdala and cerebellum

    • Nonassociative learning: Reflex pathways

    • Spatial memory: Hippocampus and cortex

• Short-term memory (working memory): Prefrontal cortex

Neuroplasticity

• Neuroplasticity: The ability of the nervous system to change in response to experience or environment. It's the basis of learning.

• Synaptic plasticity: Plastic changes at the level of synapses that can be physiological and/or structural.

Synaptic Changes

• Synaptic changes can be measured physiologically and may be presynaptic, postsynaptic, or both:

  • Increased neurotransmitter release

  • Inactivation of the transmitter is decreased

  • A greater effect is due to changes in receptors

  • Influence by other neurons

Long-Term Memories

• Long-term memories may also involve structural changes:

  • New synaptic contacts can form, or some might disappear

  • Synapses can be reorganized

Brain Changes Due to Experiences and Learning

• Interaction with an enriched environment has measurable effects on the brain, stress reactions, and learning.

Dendritic Branching

• Different housing conditions change dendritic branching.

• Enriched condition: More branches

• Standard condition: Baseline branches

• Impoverished condition: Fewer branches

Brain Changes in Enriched Conditions (EC)

• Animals housed in EC developed:

  • Heavier, thicker cortex

  • Enhanced cholinergic activity

  • More dendritic branches and spines on cortical neurons

  • Larger cortical synapses

  • More neurons in the hippocampus

  • Enhanced recovery from brain damage

Synaptic Plasticity During Habituation in Aplysia

• Non-associative learning: Involves only one stimulus.

Habituation

• Habituation: A decrease in response to a repeated stimulus.

  • A squirt of water on its siphon causes it to retract its gill. After repeated squirts, the animal retracts the gills less.

Sensitization

• Sensitization: An increase in response to the same or a smaller stimulus following a repeated stimulus.

Aplysia Habituation

• After repeated squirts, Aplysia retracts the gills less: short-term habituation involves synaptic changes between the sensory cell in the siphon and the motor neuron that retracts the gill.

• With repeated habituation over several days, each day the animal habituates faster than it did before: long-term habituation.

Short-term vs. Long-term

• Less transmitter released by sensory neuron → short-term habituation

• Fewer synapses → long-term habituation

Hebb Rule

• D. Hebb proposed that when two neurons are repeatedly activated together, their synaptic connection will become stronger.

• Hebbian synapses could act together to store memory traces.

• "Neurons that fire together, wire together"

Long-Term Potentiation (LTP)

• LTP occurs at pathways in the hippocampal formation—including the dentate gyrus—as well as in other brain regions.

LTP in the Hippocampus

• Electrodes are placed within the perforant path for stimulation of presynaptic axons.

• Record the electrical response of a group of postsynaptic neurons in the dentate gyrus.

Long Term Potentiation (LTP)

• Low-level activation of the presynaptic cells produces stable and predictable Excitatory Postsynaptic Potentials (EPSPs).

• When a brief high-frequency burst of electrical stimuli (tetanus) is applied to the presynaptic cells, causing them to produce a high rate of action potentials, the response of the postsynaptic neurons changes.

• LTP can last for weeks or more.

Receptors

• NMDA and AMPA receptors on the postsynaptic membrane – both are permeable to $Na^+$

• NMDA is also permeable to $Ca^{2+}$

• NMDA receptor is blocked by $Mg^{2+}$

LTP Process

• Before LTP, the presynaptic neuron is firing at a lower rate. Glutamate binds to the postsynaptic cell, allowing for some $Na^+$ to come in (AMPA).

• Repeated stimulation causes a higher frequency action potential → more glutamate is released (tetanus).

• $AMPA$ receptors remain open longer because there’s more glutamate which causes influx of $Na^+$

• Postsynaptic cell depolarizes.

• $Mg^{2+}$ ions pop out due to the repelling positive charges since the inside of the cell is highly depolarized.

• Once the $Mg^{2+}$ ion block pops out, an influx of $Ca^{2+}$ and $Na^+$ comes in through the NMDA.

Induction of LTP

• Influx of $Ca^{2+}$ activates intracellular enzymes, causing changes in AMPA receptors:

  • Existing receptors move to the active synapse (increased conductance of ions)

  • Activate retrograde signal to increase neurotransmitter release

Enhanced Synapse After Induction of LTP

• More AMPA receptors → postsynaptic neuron is more reactive to glutamate

Synaptic Strengthening

• Synapses that are strengthened will drive postsynaptic cell.

• Synapses that are not strengthened will become weaker and fade away.

• "Neurons that fire together, wire together"