Long-term potentiation (LTP) at glutamatergic synapses in the hippocampus requires coincident activity in both pre- and postsynaptic neurons. The molecular 'coincidence detector' that enables this is:

• A AMPA receptor, which depolarizes the postsynaptic membrane only when sufficient presynaptic glutamate binds
• B Metabotropic mGluR5 receptor activating IP3 cascade only during repetitive stimulation
• C NMDA receptor, which requires both glutamate binding (presynaptic activity) AND postsynaptic depolarization (to remove Mg2+ block) for Ca2+ influx — acting as a Hebbian coincidence detector ✓
• D Kainate receptor selectively activated during high-frequency stimulation patterns

Explanation

The NMDA (N-methyl-D-aspartate) receptor is the critical coincidence detector for LTP induction. At resting membrane potential, NMDA receptor channels are blocked by Mg2+ (voltage-dependent block). NMDA receptors require two simultaneous conditions to open: (1) glutamate binding from presynaptic release (ligand-gating); (2) sufficient postsynaptic depolarization (usually via AMPA receptor activation) to expel the Mg2+ block. When both conditions are met (coincident pre- and postsynaptic activity), Ca2+ flows through NMDA channels, activating CaMKII, which phosphorylates AMPA receptors to increase their conductance and drives AMPA receptor insertion into the synapse — thus potentiating synaptic transmission. This NMDA receptor property embodies Hebb's postulate ('cells that fire together, wire together').

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

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