NR2B tyrosine phosphorylation modulates fear learning as well as amygdaloid synaptic plasticity

Phosphorylation of neural proteins in response to a diverse array of external stimuli is one of the main mechanisms underlying dynamic changes in neural circuitry. The NR2B subunit of the NMDA receptor is tyrosine‐phosphorylated in the brain, with Tyr‐1472 its major phosphorylation site. Here, we generate mice with a knockin mutation of the Tyr‐1472 site to phenylalanine (Y1472F) and show that Tyr‐1472 phosphorylation is essential for fear learning and amygdaloid synaptic plasticity. The knockin mice show impaired fear‐related learning and reduced amygdaloid long‐term potentiation. NMDA receptor‐mediated CaMKII signaling is impaired in YF/YF mice. Electron microscopic analyses reveal that the Y1472F mutant of the NR2B subunit shows improper localization at synapses in the amygdala. We thus identify Tyr‐1472 phosphorylation as a key mediator of fear learning and amygdaloid synaptic plasticity.