Long-term potentiation (LTP) at hippocampal synapses requires initial AMPA receptor activation to relieve Mg2+ block from NMDA receptors. Which molecule acts as the 'coincidence detector' in LTP induction?
- A AMPA receptor, which undergoes Ca2+ permeability change on repeated stimulation
- B NMDA receptor, which requires simultaneous glutamate binding (ligand) and membrane depolarisation (voltage) for Ca2+ entry ✓
- C mGluR5 (metabotropic glutamate receptor), activating IP3 to release intracellular Ca2+
- D Kainate receptor, which provides high-frequency summation for LTP threshold
Explanation
The NMDA receptor is the classic coincidence detector of LTP. At resting membrane potential, the channel pore is blocked by Mg2+. When presynaptic glutamate is released AND the postsynaptic membrane is simultaneously depolarised (by AMPA-mediated EPSPs), the Mg2+ block is relieved. Only then can glutamate open the NMDA channel to allow Ca2+ influx, which activates CaMKII, triggers AMPA receptor phosphorylation and insertion, and initiates the signalling cascade for LTP. This dual requirement (ligand + voltage) is the molecular basis of associativity in Hebbian learning.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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