Lecture Notes on Synaptic Plasticity and the Hippocampus

Introduction

• Focus on long-term synaptic plasticity in the hippocampus.
• Importance of the hippocampus in memory functions.
• Anatomy: Located at the temporal lobe, with three main regions: CA1, CA3 (pyramidal neurons), and the dentate region (granule neurons).

Hippocampal Circuitry

• Input Pathways:
  • Perforant pathway connects to granule and CA1 cells.
  • Mossy fiber pathway from granule cells to CA3 cells.
  • Schaffer collateral pathway from CA3 to CA1 cells.
• Textbooks often flip hippocampal diagrams, actual orientation based on coronal sections.

Long-Term Plasticity

• Types:
  • Long-Term Potentiation (LTP): Strengthens synaptic connections.
  • Long-Term Depression (LTD): Weakens synaptic connections.

Mechanism of LTP

• Key Experiment: Shaffer collateral synapse between CA3 and CA1.
• Excitatory synapse mediated by glutamate.
• Protocol:
  • Low-frequency stimulation results in baseline EPSP.
  • High-frequency stimulation (tetanus) increases EPSP, showing potentiation.
• Role of NMDA Receptors:
  • Dependent on both glutamate binding and postsynaptic depolarization.
  • AP5 blocks NMDA receptors, preventing LTP.
• Calcium Signaling:
  • Calcium entry through NMDA receptors activates kinases (PKC, CAMKII).
  • Leads to phosphorylation, AMPA receptor insertion, and enhanced postsynaptic response.

Early vs. Late LTP

• Early LTP:
  • Lasts a few hours, involves AMPA receptor trafficking.
• Late LTP:
  • Requires gene expression and protein synthesis.
  • Involves PKA, MAPK, and CREB.
  • New synaptic contacts form over longer periods.

Properties of LTP

• Input Specificity: LTP occurs only at stimulated synapses.
• Cooperativity: Multiple weak pathways can together induce postsynaptic firing.
• Associativity: Strong pathway can aid weak pathways in inducing LTP.
• Homosynaptic vs. Heterosynaptic Plasticity:
  • Homosynaptic: Changes occur at stimulated synapse.
  • Heterosynaptic: Changes at unstimulated synapse.

Mechanism of LTD

• Induced by low-frequency stimulation.
• Requires calcium entry through NMDA receptors.
• Activates phosphatases (PP1, calcineurin) which lead to AMPA receptor removal.

Spike Timing-Dependent Plasticity (STDP)

• Mechanism:
  • Involves precise timing of pre- and postsynaptic spikes.
  • LTP induced if presynaptic spike precedes postsynaptic.
  • LTD induced if presynaptic spike follows postsynaptic.

Underlying Mechanism

• Based on NMDA receptor activation.
• Back Propagation: Action potentials can travel back to dendrites, aiding NMDA receptor activation.

Hebbian Learning Principle

• Hebb’s Postulate: "Cells that fire together wire together."
• Extension: Synaptic efficacy decreases if presynaptic cell does not contribute to postsynaptic firing.

Conclusion

• Key Concepts: Cooperativity, associativity, input specificity are crucial for memory formation.
• STDP: Refines synaptic connections in development, explained by NMDA receptor activity.

These notes summarize the key points discussed in the lecture on synaptic plasticity and the hippocampal circuitry.