Long-term potentiation (LTP) in hippocampal CA1 neurons requires coincident pre- and postsynaptic activity. The molecular detector of this coincidence is the NMDA receptor acting as a 'coincidence detector' because:

• A It requires both glutamate binding (presynaptic signal) AND postsynaptic depolarization to relieve Mg²⁺ block, allowing Ca²⁺ influx that activates CaMKII ✓
• B It is activated only by AMPA receptor-mediated depolarization that opens GABA channels, linking pre- and postsynaptic activity
• C It detects coincidence through PKA phosphorylation of AMPA receptors triggered by simultaneous dopamine and glutamate binding
• D It requires co-activation of mGluR1 (metabotropic) and kainate receptors for IP3-mediated Ca²⁺ release to trigger LTP

Explanation

The NMDA receptor is the molecular coincidence detector for LTP. At resting membrane potential, the NMDA receptor channel is blocked by Mg²⁺ even when glutamate is bound. Postsynaptic depolarization (typically by prior AMPA receptor activation) displaces the Mg²⁺ block. When BOTH conditions are met simultaneously — glutamate from the presynaptic terminal AND postsynaptic depolarization — the NMDA channel opens, allowing massive Ca²⁺ influx. Elevated Ca²⁺ activates CaMKII (Ca²⁺/calmodulin-dependent kinase II), which phosphorylates AMPA receptors and triggers their trafficking to the synapse, increasing synaptic strength. This Hebbian 'fire together, wire together' mechanism underlies memory encoding.

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

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