Serotonergic control of valence processing in amygdalo- striaterminalis circuits

Valence, a hedonic value assigned to sensory stimuli that determines subsequent behaviors, is a fundamental organizing principle of affective states and emotional behaviors. Valence influences physiological processes across multiple organ systems — effects that may be mediated in part by the serotonergic (5-HT) system, which itself has widespread distribution throughout the body. The brain serotonergic system projects to the amygdala and its extended structure, the bed nucleus of the stria terminalis (BNST), regions heavily implicated in valence encoding. Despite their anatomical and functional connectivity, the amygdala and BNST express distinct 5-HT receptor subtypes, receive heterogeneous 5-HT projections, and process valence differently. The current study examines the significance of 5-HT projections in the computation of valence in the CeA and BNST. Here, multi-site in vivo electrophysiology was combined with anterograde chemogenetic modulation of 5-HT terminals in either the BNST or the CeA, while recording from both regions during valence presentation tasks where mice were exposed to the odorants of saline (neutral), opposite-sex urine (positive), and trimethylthiazoline (TMT, negative valence) in a counterbalanced manner. Neural responses were then compared across the neutral, appetitive, and aversive stimuli. Our results showed dorsal raphe 5-HT activation in the BNST supported valence coding in the CeA and BNST during stimulus presentation. During the post-stimulus phase, this modulation engaged only CeA-supported valence coding. Conversely, the inhibition of 5-HT terminals in the BNST supported local valence coding. Dorsal raphe 5-HT activation in the CeA enhanced valence coding in both the CeA and BNST only after stimulus offset. However, its suppression in the CeA enhanced valence coding in both the CeA and BNST during and after stimulus presentation. Taken together, our results showed that dorsal raphe serotonergic modulation creates a phasic response pattern in the CeA/BNST circuit by moderating response timing relative to stimulus valence.