Sex differences in oscillatory signaling dynamics in the prelimbic cortex and nucleus accumbens core during negative affect.

Affective processing is important for guiding behavior and its dysfunction can lead to several psychiatric illnesses, including depression and substance use disorders. Conditioned taste aversion (CTA) is used to study learned shifts in affect, and taste reactivity (TR) can effectively track the hedonic properties of appetitive and aversive tastants before and after CTA. While the infralimbic cortex (IL) and its projections to the nucleus accumbens (NAc) shell play a key role in learned negative affect, this role is unique to males. Here, we sought to determine if the prelimbic cortex (PrL) to nucleus accumbens (NAc) core circuit, another prefrontal cortex-accumbens system, tracks innate versus learned negative affect using electrophysiological (local field potential, LFP) methods in male and female rats. As expected, CTA elicited a hedonic shift from an appetitive to an aversive TR profile, regardless of sex. However, time-frequency analyses revealed differential activity in the PrL and NAc core during innate and learned negative affect across sex. Specifically, we found that beta oscillations in the NAc core encode learned negative affect in males, while neither brain region seems to be selectively attuned to innate or learned aversion in females. Importantly, LFP functional connectivity (coherence) indicated that the PrL-NAc core circuit does not track any aspect of learned negative affect in either sex but may be involved in innate aversion in males only. Collectively, these data provide a sex-specific understanding of real-time oscillatory signaling dynamics in the PrL and NAc core during innate versus learned negative affect.