eLife Assessment: Functional specialization of mPFC–BLA and mPFC–NAc pathways in affective state representation

Effective emotional processing, crucial for adaptive behavior, is mediated by the medial prefrontal cortex (mPFC) via connections to the basolateral amygdala (BLA) and nucleus accumbens (NAc), traditionally considered functionally similar in modulating reward and aversion responses. However, the functional specialization of the mPFC→BLA and mPFC→NAc pathways in representing affective states remains unclear. We found that while overall firing patterns appeared consistent across emotional states, deeper analysis revealed distinct variabilities. Specifically, mPFC→BLA neurons, especially “center-ON” neurons, exhibited heightened activity during behaviors classically associated with anxiety-like states, suggesting their involvement in aversive behavioral regulation. Conversely, mPFC→NAc neurons were more active during exploratory and approach-related behaviors, implicating them in the processing of positively valenced behavioral states. Notably, mPFC→NAc neurons showed significant pattern decorrelation during social interactions, suggesting a pivotal role in processing social preference. Additionally, chronic emotional states affected these pathways differently: positively valenced contexts enhanced mPFC→NAc activity, while negatively valenced conditions boosted mPFC→BLA activity. These findings challenge the assumed functional similarity and highlight distinct correlational patterns, suggesting potential, but not yet causally established, roles of mPFC→BLA and mPFC→NAc pathways in shaping emotional states.