Long-term potentiation (LTP) in the hippocampus requires activation of NMDA receptors. The NMDA receptor's unique 'coincidence detector' property means it requires both:

• A Glutamate binding (ligand-gated) AND postsynaptic membrane depolarization to relieve Mg2+ block (voltage-gated) — both required simultaneously ✓
• B Simultaneous GABA binding and membrane hyperpolarization to activate
• C Dopamine binding and cAMP generation to phosphorylate the receptor
• D Only presynaptic glutamate release — no postsynaptic conditions are required

Explanation

NMDA receptors are dual-gated channels requiring both ligand binding (glutamate + glycine as co-agonist) AND postsynaptic membrane depolarization. At resting membrane potential, a Mg2+ ion blocks the NMDA channel pore. When the membrane is depolarized (by AMPA receptor activation from high-frequency stimulation), Mg2+ is expelled, allowing Ca2+ influx through the now-unblocked NMDA channel. This Ca2+ influx triggers kinase-dependent changes that increase AMPA receptor numbers and conductance, forming the basis of LTP and hippocampal-dependent memory formation.

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

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