Decoding the hidden variabilities in mPFC descending pathways across emotional states.

Effective emotional regulation, 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, how the mPFC balances these descending pathways to control behavioral outcomes 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 anxiety-related behaviors, highlighting their role in anxiety encoding. Conversely, mPFC→NAc neurons were more active during exploratory behaviors, implicating them in processing positive emotional states. Notably, mPFC→NAc neurons showed significant pattern decorrelation during social interactions, suggesting a pivotal role in encoding social preference. Additionally, chronic emotional states affected these pathways differently: positive states enhanced mPFC→NAc activity, while negative states boosted mPFC→BLA activity. These findings challenge the assumed functional similarity and highlight distinct contributions to emotional regulation, suggesting new avenues for therapeutic interventions.