Long-term potentiation (LTP) in the hippocampus requires NMDA receptor activation. Which molecular event is the essential gate that allows NMDA receptors to conduct current?

• A Coincidence detection: simultaneous glutamate binding AND post-synaptic depolarization (to relieve Mg2+ block of the channel pore) is required ✓
• B Glutamate binding alone is sufficient to open NMDA receptors at resting membrane potential
• C Glycine binding as a co-agonist is the sole rate-limiting step for NMDA receptor activation
• D Phosphorylation of the NR2B subunit by CAMKII is required before glutamate can bind

Explanation

NMDA receptors are molecular coincidence detectors: they require both ligand binding (glutamate at the NR2 subunit and glycine/D-serine at the NR1 subunit) AND post-synaptic membrane depolarization. At resting potential (~-70 mV), the channel pore is blocked by Mg2+; sufficient depolarization (from AMPA receptor activation) removes this Mg2+ block. When both conditions are met simultaneously, Ca2+ enters the post-synaptic neuron through the NMDA channel, activating CaMKII and other kinases that phosphorylate AMPA receptors and trigger LTP induction — the cellular basis of learning and memory.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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