Prelimbic proBDNF Facilitates Retrieval-Dependent Fear Memory Destabilization by Regulation of Synaptic and Neural...

Fear regulation changes as a function of the early life is a key developmental period for the continued maturation of fear neural circuitry. The mechanisms of fear retrieval-induced reconsolidation have been investigated but remain poorly understood. The involvement of prelimbic proBDNF in fear memory extinction and its mediated signaling have been reported previously. Specifically, blocking the proBDNF/p75^NTR pathway during the postnatal stage disrupts synaptic development and neuronal activity in adulthood. Given the inherent high expression of proBDNF during the juvenile period, we tested whether the prelimbic proBDNF regulated synaptic and neuronal functions allowing to influencing retrieval-dependent memory processing. By examining the freezing behavior of auditory fear-conditioned rats, we found the high level of the prelimbic proBDNF in juvenile rats enhanced the destabilization of the retrieval-dependent weak but not strong fear memory through activating p75^NTR-GluN2B signaling. This modification of fear memory traces was attributed to the increment in the proportion of thin-type spine and promotion in synaptic function, as evidenced by the facilitation of NMDA-mediated EPSCs and GluN2B-dependent synaptic depression at the prelimbic projection. Furthermore, the strong prelimbic theta- and gamma-oscillation coupling predicted the suppressive effect of juvenile proBDNF on the recall of postretrieval memory. Our results critically emphasize the importance of developmental proBDNF for modification of retrieval-dependent memory and provide a potential critical targeting to inhibit threaten memories associated with neurodevelopment disorders.