摘要：SummaryTargeting memory reconsolidation is an effective intervention for treating posttraumatic stress disorder (PTSD). Disrupting unconditioned stimulus (US)-retrieval-induced fear memory reconsolidation has become an effective therapeutic approach to attenuate fear memory, but the underlying molecular mechanisms remain unknown. Here, we report that US-retrieval-dependent increase in phosphatidylinositol 4-kinase IIα (Pi4KIIα) promotes early endosomal trafficking of AMPA receptors, leading to the enhancement of synaptic efficacy in basolateral amygdala (BLA) neurons. The inhibition of Pi4KIIα by an inhibitor or short hairpin RNA impaired contextual fear memory reconsolidation. This disruptive effect persisted for at least 2 weeks, which was restored by Pi4KIIα overexpression with TAT-Pi4KIIα. Furthermore, the blockade of early endosomal trafficking following US retrieval reduced synaptosomal membrane GluA1 levels and decreased subsequent fear expression. These data demonstrate that Pi4KIIα in the BLA is crucial for US-retrieval-induced fear memory reconsolidation, the inhibition of which might be an effective therapeutic strategy for treating PTSD.Graphical AbstractDisplay OmittedHighlights•Unconditioned stimulus (US) retrieval induces a transient increase in Pi4KIIα expression•Pi4KIIα regulates early endosomal trafficking of AMPARs during memory reconsolidation•Pi4KIIα contributes to US-retrieval-induced synaptic enhancement in rat BLA•Pi4KIIα inhibition after US retrieval impairs fear expression and shows long-term effectsBehavioral Neuroscience; Molecular Neuroscience; Cellular Neuroscience
