The Role Of The Medial Prefrontal Cortex In The Contextual Fear Memory Of Rats Using Optogenetics

Jeffrey B. RosenThe medial prefrontal cortex (mPFC) has previously been shown to play various roles in different phases of fear-learning and memory, particularly in extinction. While there has been substantial progress in understanding how the mPFC regulates fear to discrete cues (e.g., tones and lights), less is known about the mPFC’s involvement in learning fear to a context. Therefore, this study examined the effects of mPFC inhibition during the acquisition phase of contextual fear conditioning on the long-term retention and extinction of contextual fear. Twenty-four rats received bilateral infusions of a pan-cellular optogenetic neural silencer CAG-ArchT-EGFP (ArchT, n=12) or a CAG-EGFP (control, n=12) virus. Three weeks later, optic fiber assemblies (OFAs) were bilaterally implanted over the injection site. After an additional week of recovery, rats were conditioned using a contextual fear conditioning paradigm administering 5 shocks, each 3 minutes apart on day one and tested for freezing to the context-alone on days two and three. The mPFC was optogenetically inhibited on day one during contextual fear acquisition. Optogenetic inhibition of mPFC during the acquisition phase of contextual fear conditioning (Day 1) did not significantly affect the increases in freezing to the context or the rate of acquisition. The control rats showed significantly decreased freezing levels compared to the sustained increased freezing levels of the ArchT rats during day 2 of the extinction retention test. On the second extinction retention test, there was a similar trend in decreased freezing of the control rats. In an alternate context, rats were subsequently reconditioned and extinction tested. ArchT rats showed significantly higher freezing levels before shocks began, but showed no significantly different training and extinction testing behavior compared to controls, indicating that optogenetic silencing did not cause permanent inhibition to the mPFC. These data suggest that inhibition of the mPFC activity during acquisition interferes with later extinction and facilitates fear generalization to a novel context.Neuroscienc