Reduction of Excitatory Synaptic Transmission Efficacy in the Infralimbic Prefrontal Cortex Potentially Contributes to Impairment of Contextual Fear Memory Extinction in AgedMice.

Abstract

Human beings are living longer than ever before and thecognitive decline experienced by aged adults, such as compromise in cognitive flexibility, has been attracting more and more attention. One such example is the aging-related impairment of memory extinction. However, its underlying neural basis, especially its functional basis at the synapse level, is largely unknown. This study verifies that Pavlovian contextual fear memory extinction is impaired in aged mice. Alarge body of previous studies has shown that the infralimbic prefrontal cortex (ilPFC) plays a pivotal role in memory extinction. Correspondingly, this study reveals an aging-related reduction in the efficacy of excitatory synaptic transmission onto the ilPFC pyramidal neurons via electrophysiology recordings. This study further suggests that this reduced excitation potentially contributes to the aging-related impairment of contextual fear memory extinction: chemogenetically suppressing the activity of the ilPFC pyramidal neurons in young mice impairs contextual fear memory extinction, whereas chemogenetically compensating forthe reduced excitation of the ilPFC pyramidal neurons in aged mice restores contextual fear memory extinction. This study identifies a functional synaptic plasticity in the ilPFC pyramidal neurons that potentially contributes to the aging-related impairment of contextual fear memory extinction, which would potentially help to develop a therapy to treat related cognitive decline in aged human adults.