Long-term potentiation (LTP) in the hippocampus is the cellular substrate of declarative memory formation. Which molecular sequence is correct for the induction of LTP?

• A Presynaptic GABA release → GABA-A receptor activation → Cl− influx → postsynaptic depolarization → NMDA activation → LTP
• B AMPA receptor activation leads directly to gene expression changes without requiring NMDA receptor involvement
• C Ca2+ influx via voltage-gated Ca2+ channels on presynaptic terminal → increased glutamate release → postsynaptic AMPA receptor upregulation
• D Strong presynaptic stimulation → sufficient glutamate release → AMPA receptor activation depolarizes postsynaptic membrane → Mg2+ block removed from NMDA receptor → Ca2+ influx through NMDA receptor → activation of CaMKII → AMPA receptor phosphorylation/insertion → LTP ✓

Explanation

LTP induction requires coincident presynaptic and postsynaptic activity (Hebb's rule). Glutamate acts on both AMPA receptors (causing depolarization) and NMDA receptors (normally blocked by Mg2+ at rest). When sufficient AMPA-mediated depolarization occurs, the Mg2+ block is relieved, allowing Ca2+ to flow through NMDA receptors. Ca2+ activates CaMKII (and other kinases), which phosphorylates existing AMPA receptors and recruits additional ones to the synapse, increasing synaptic strength. Longer-term LTP involves PKA, MAPK pathways, CREB-driven gene expression, and dendritic spine growth.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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