Which of the following best characterizes the canonical mechanism of NMDA receptor–dependent long-term depression (LTD) in hippocampal CA1 neurons?

Question

BlackTom AI · Accepted Answer

Question restatement: The prompt asks which option best characterizes the canonical mechanism of NMDA receptor–dependent long-term depression (LTD) in hippocampal CA1 neurons.
Option 1: 'Activation of mGluR triggers MAPK signaling, leading to postsynaptic removal of NMDA receptors.' While metabotropic glutamate receptor (mGluR) signaling can contribute to other forms of synaptic plasticity, this description does not match the classic NMDA receptor–dependent LTD mechanism in CA1, which centers on calcium-dependent phosphatase activity rather than mGluR-MAPK pathways.
Option 2: 'AMPA receptor phosphorylation by PKA promotes receptor recycling and stabilizes synaptic weakening.' Phosphorylation by PKA generally biases toward receptor trafficking that can support LTP-like processes or receptor recycling, not the canonical LTD pathway driven by phosphatases removing AMPA receptors; thus this option mischaracterizes the main LTD mechanism.
Option 3: 'Large calcium influx through NMDA receptors activates CaMKII, strengthening AMPA receptor insertion at the postsynaptic density.' This describes a mechanism more aligned with long-term potentiation (LTP), where CaMKII activity promotes AMPA receptor insertion and synaptic strengthening, not LTD. Therefore, it describes the opposite of LTD.
Option 4: 'Modest, sustained calcium influx through NMDA receptors activates protein phosphatases such as PP1 and calcineurin, leading to AMPA receptor internalization.' This aligns precisely with the canonical NMDA receptor–dependent LTD in CA1: a limited, prolonged Ca2+ signal preferentially activates phosphatases (PP1, calcineurin) that dephosphorylate substrates and promote internalization of AMPA receptors, resulting in synaptic weakening.
In summary, options 1–3 describe pathways that either do not match NMDA receptor–dependent LTD or describe processes characteristic of other forms of plasticity (mGluR-related signaling, PKA-led recycling, or CaMKII-mediated LTP). Option 4 accurately reflects the well-established LTD mechanism involving modest Ca2+ influx, phosphatase activation, and AMPA receptor internalization.

Which of the following best characterizes the canonical mechanism of NMDA receptor–dependent long-term depression (LTD) in hippocampal CA1 neurons?单项选择题

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