Physiology · Neurophysiology (Synapse, Action Potential, Tracts, Reflexes)

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is critical for memory formation. The initial requirement for NMDA receptor activation during LTP induction depends on which co-requirement?

  • A Presynaptic vesicle release of glycine to co-activate NMDA receptors in place of glutamate
  • B Retrograde NO signaling from the postsynaptic cell enhancing presynaptic glutamate release first
  • C Simultaneous postsynaptic depolarization sufficient to relieve Mg2+ block of NMDA receptor channels, allowing Ca2+ influx
  • D mGluR activation leading to IP3-mediated intracellular Ca2+ release that then opens NMDA receptors
Correct answer: C. Simultaneous postsynaptic depolarization sufficient to relieve Mg2+ block of NMDA receptor channels, allowing Ca2+ influx

Explanation

NMDA receptors are coincidence detectors: they require simultaneous glutamate binding AND postsynaptic depolarization. At resting membrane potential, the NMDA receptor channel pore is physically blocked by Mg2+ ions. Only when the postsynaptic membrane is sufficiently depolarized (typically by concurrent AMPA receptor activation from strong stimulation) is Mg2+ expelled from the channel, allowing Ca2+ influx. This Ca2+ influx activates CaMKII and other kinases, which phosphorylate AMPA receptors and promote their insertion into the synapse, increasing synaptic strength — the synaptic basis of Hebbian learning.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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