Long-term potentiation (LTP) in hippocampal CA1 neurons requires NMDA receptor activation. Which molecular event is the essential gate for NMDA receptor opening that makes LTP coincidence-dependent (Hebbian)?

• A Presynaptic release of dopamine alongside glutamate is required to displace the Zn²⁺ block of NMDA receptors before Ca²⁺ entry can occur
• B Postsynaptic hyperpolarisation is required to remove the Na⁺ block and allow Ca²⁺ to enter through NMDA channels
• C AMPA receptor phosphorylation by PKC is required before NMDA receptor Mg²⁺ block is relieved, making LTP depend on prior PKC activation rather than membrane voltage
• D Postsynaptic membrane depolarisation (produced by prior AMPA receptor activation) expels the Mg²⁺ ion blocking the NMDA receptor channel pore; only then can glutamate + glycine co-binding open the channel to allow Ca²⁺ influx that activates CaMKII for LTP ✓

Explanation

NMDA receptors have a voltage-dependent Mg²⁺ block: at resting membrane potential, Mg²⁺ physically occludes the ion channel pore despite ligand binding. Only when the postsynaptic membrane is sufficiently depolarised (by AMPA receptor-mediated Na⁺ entry or back-propagating action potentials) does the electrostatic force expelling the Mg²⁺ block allow glutamate and its co-agonist glycine (or D-serine) to open the channel and permit Ca²⁺ influx. This voltage-and-ligand coincidence requirement makes NMDA receptors 'coincidence detectors' — they open only when both pre- and postsynaptic neurons are simultaneously active (Hebb's rule). Ca²⁺ influx activates CaMKII → AMPA receptor phosphorylation/insertion → LTP. Dopamine modulates LTP but is not required for Mg²⁺ block removal.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.