Prelimbic proBDNF facilitates memory destabilization by regulation of neuronal function in juveniles

Abstract

Fear regulation changes as a function of age and adolescence is a key developmental period for the continued maturation of fear neural circuitry. The involvement of prelimbic proBDNF in fear memory extinction and its mediated signaling were reported previously. Given the inherent high level of proBDNF during juvenile period, we tested whether prelimbic proBDNF regulated synaptic and neuronal functions allowing to influencing retrieval-dependent memory processing. By examining freezing behavior of auditory fear conditioned rats, we found high levels of prelimbic proBDNF in juvenile rats enhanced destabilization of the retrieval-dependent weak but not strong fear memory through activating p75NTR-GluN2B signaling. This modification was attributed to the increment in proportion of thin type spine and promotion in synaptic function, as evidence by facilitation of NMDA-mediated EPSCs and GluN2B-dependent synaptic depression. The strong prelimbic theta- and gamma-oscillation coupling predicted the suppressive effect of proBDNF on the recall of post-retrieval 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.