High Gamma Activity in the Infralimbic Cortex to Nucleus Accumbens Shell Pathway Modulates Innate Aversion Differentially across Sex

Aversion modulation is a key component of hedonic processing, and its dysfunction is evident in psychiatric illnesses. The infralimbic cortex (IL) to nucleus accumbens shell (NAcSh) pathway is essential in hedonic processing in rodents but operates differentially across sex, with beta (20 Hz) oscillatory activity involved in learned aversion in male but not female rats. In this study, we used taste reactivity (TR) and electrophysiology to examine the role of high gamma (80 Hz) activity in affect modulation, specifically innate (quinine) and learned (conditioned taste aversion, CTA) aversion, in male and female Sprague Dawley rats. Local field potential (LFP) recordings in males showed no changes in IL or NAcSh activity, or in IL→NAcSh functional connectivity, in the high gamma frequency band during innate or learned aversion. In contrast, in females, quinine elicited an increase in IL and NAcSh 80 Hz LFP activity and IL→NAcSh functional connectivity. Interestingly, LFP directionality analyses in females indicated that top-down modulation from IL to NAcSh was associated with innate aversive behavior expression. To confirm a causal link of 80 Hz activity in aversion processing in females, optogenetics was used. Here, optogenetic stimulation of the IL→NAcSh pathway did not affect learned (CTA) aversion but it selectively decreased innate (quinine) aversion. Collectively, these results highlight sex- and frequency-specific differences in aversion modulation by the IL→NAcSh pathway, with high gamma frequencies involved in modulating innate aversion, specifically in female rats.