Foundations of Neuroscience week 14 Notes

Major Concepts in Learning and Memory

1. Memory Systems and Structures

• Focus Areas: Memory, Structures, and Systems, including directed learning through the temporal lobe and hippocampal system.

• Role of the Medial Temporal Lobe (MTL):

  • Function: Initially links diverse cortical attributes of events, allowing the integration of various sensory experiences into a coherent memory.

  • Stimulation: Activation in this area can evoke vivid memories and sensations, indicating its critical role in memory recall.

  • Post-consolidation: After the process of consolidation, these links revert to cortical areas for more efficient recall of previously learned information.

2. Experimental Insights

• Lashley’s Rat Lesion Experiments (1920s):

  • Key Findings: Investigated the relationship between lesions in the cortex and memory deficits in rats completing maze tasks.

  • Observation: Severity of memory impairment correlated with lesion size rather than specific location in the cortex.

  • Equipotentiality Theory: Proposed that multiple cortical areas contribute equally to memory functions, challenging ideas that specific areas are strictly responsible for memories.

• Penfield’s Experiments:

  • Findings: Direct electrical stimulation of the MTL in patients evoked hallucinatory sensations or vivid recollections, reinforcing the significance of this area in episodic memory formation.

• Patient H.M.:

  • Background: An individual with severe epilepsy underwent surgical removal of portions of his bilateral medial temporal lobes (including the hippocampus and amygdala).

  • Outcome: Resulted in profound anterograde amnesia (inability to form new memories) and retrograde amnesia (loss of past memories), despite intact procedural memory (skills learned).

  • Implications: Provided crucial insights into the differential roles of various brain regions in types of memory.

3. Learning Mechanisms

• Hebbian Learning:

  • Hebb Rule: A foundational principle describing how synaptic strength increases when an action potential in one neuron is followed by an action potential in another. Essentially states: “Cells that fire together, wire together.”

  • Cell Assembly: A network of interconnected cortical neurons that activates as a unit to represent external events, facilitating memory formation.

• Neurobiological Mechanisms:

  • Long-term potentiation (LTP):

  • Induction: Resulting from high-frequency stimulation leading to sustained increases in synaptic strength, an essential process for memory encoding and retention.

  • Long-term depression (LTD):

  • Induction: Resulting from low-frequency stimulation, leading to a decrease in synaptic strength, crucial for clearing out excess connections to refine learned information.

  • NMDA Receptors:

  • Critical for mediating calcium influx during neuronal depolarization, necessary for synaptic modifications that underpin learning and memory.

  • BCM Theory:

  • Synaptic strength adjustments are contingent on calcium levels in postsynaptic cells, dictating whether LTP or LTD occurs based on the firing rate of presynaptic neurons.

4. Physiological Studies on Learning

• Radial Arm Maze Studies:

  • Normal rats can effectively remember food locations within the maze, visiting each arm only once and demonstrating the hippocampus's role in working memory and spatial navigation.

  • Rats with hippocampal lesions exhibit deficits, often revisiting arms after collecting food, showcasing the hippocampus's functionality in memory retention.

• Aplysia Studies:

  • Known for its simple nervous system, the sea slug Aplysia was utilized to study the gill withdrawal reflex.

  • Experiments by Eric Kandel: Mechanical stimulation leads to gill withdrawal as a defense mechanism, providing insights into synaptic changes related to learning and memory, earning him a Nobel Prize in 2000.

  • Habituation and Sensitization:

  • Habituation: A decrease in response to a repeated stimulus due to synaptic modifications;

  • Sensitization: An enhanced response to a stimulus following a strong or noxious stimulus, illustrating changes in synaptic strength.

5. Molecular Mechanisms

• Synaptic Transmission:

  • The process involves several key steps including:

  1. Vesicle Docking: SNARE proteins facilitate the fusion of synaptic vesicles with the presynaptic membrane.

  2. Presynaptic Calcium Influx: Triggered by action potentials arriving at the axon terminal.

  3. Exocytosis: The release of neurotransmitters into the synaptic cleft.

  4. Membrane Recycling: Endocytosis of vesicular membrane after neurotransmitter release back into the presynaptic terminal.

• Neurotransmitter Release Dynamics:

  • Repeated stimulation of a synapse can lead to progressively smaller excitatory postsynaptic potentials (EPSPs) in the motor neuron, indicating changes in synaptic efficacy.

• Long-term Memory Consolidation Mechanisms:

  • Key drivers include:

  1. Persistent protein kinases that support continuous phosphorylation, necessary for maintaining memory traces.

  2. Genetic expression regulators like CREB that modulate gene expression to facilitate long-term changes in cells.

  3. Formation of new synapses through environmental stimulation, indicating a dynamic process of memory encoding influenced by external factors.

• New Synapse Formation:

  • Environmental changes stimulate the formation of dendritic spines, enhancing synaptic connections and thereby promoting memory consolidation demonstrated in rats upon exposure to novel environments.

Summary

• A comprehensive overview of the various mechanisms and stages involved in the processes of learning and memory formation, melding insights from both invertebrate and vertebrate studies focusing on synaptic changes and neural pathways involved in complex behaviors and cognitive functions