Synaptic long-term potentiation (LTP) in the hippocampus requires co-activation of AMPA and NMDA receptors. Which of the following correctly explains the 'coincidence detector' function of the NMDA receptor?

• A NMDA receptor channels are blocked by Mg²⁺ at resting membrane potential; simultaneous AMPA-mediated depolarization displaces the Mg²⁺ block, allowing Ca²⁺ influx through NMDA channels only when both presynaptic glutamate release and postsynaptic depolarization occur together ✓
• B NMDA receptors require simultaneous binding of glutamate and glycine without any voltage dependence, making them constitutively active once both agonists bind
• C NMDA channels open only when presynaptic and postsynaptic neurons fire within 50 ms in an anti-Hebbian pattern (postsynaptic before presynaptic)
• D NMDA receptor activation requires prior phosphorylation by CaMKII, which accumulates only after repeated presynaptic firing, establishing a molecular coincidence requirement

Explanation

NMDA receptors function as coincidence detectors because they require two simultaneous signals: (1) presynaptic glutamate release binding to the receptor, and (2) sufficient postsynaptic depolarization to relieve the voltage-dependent Mg²⁺ block of the channel pore. At resting potential (−70 mV), Mg²⁺ physically occludes the NMDA channel even when glutamate is bound. AMPA receptor activation by prior/concurrent synaptic input depolarizes the membrane, expelling the Mg²⁺. When both conditions are met simultaneously, the NMDA channel opens and allows Ca²⁺ (and Na⁺/K⁺) influx. Ca²⁺ activates CaMKII and other kinases, leading to AMPA receptor insertion and LTP expression. Option B is incorrect — NMDA receptors require voltage relief in addition to glutamate + glycine binding. Option C incorrectly describes the temporal requirement (LTP uses Hebbian plasticity: pre-before-post within ~20 ms). Option D reverses cause and effect; CaMKII is activated by NMDA-mediated Ca²⁺ influx, not a prerequisite for it.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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