Degree

Doctor of Philosophy (PhD)

Department

Comparative Biomedical Sciences

Document Type

Dissertation

Abstract

The serotonergic (5-HT) system is a broadly interconnected neural network that regulates valence-guided behaviors. Its prominent nucleus, the dorsal raphe nucleus (DRN), projects to brain regions including the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST), implicated in valence processing. Despite their anatomical and functional connectivity, the CeA and BNST express distinct 5-HT receptor subtypes, receive heterogeneous 5-HT projections, and play different roles in processing valence. Here, we examined the significance of distinct DRN 5-HT projections on valence processing in the BNST-CeA circuit. We sought to investigate how modulation of BNST- and CeA-projecting DRN-5-HT neurons affects neural representations of valence in the CeA and BNST, respectively, and whether these dynamics reflect valence-guided behavior.

In chapter 2, multi-site in vivo electrophysiology was combined with anterograde chemogenetic modulation of 5-HT terminals in the CeA and BNST during valence stimuli presentation. Our results showed that activation of DRN 5-HT terminals in the BNST supported valence coding in the CeA and BNST during stimulus presentation. Following stimulus termination, this modulation engaged only CeA-supported valence coding. Conversely, the inhibition of 5-HT terminals in the BNST supported local valence coding. Activation of DRN 5-HT terminals in the CeA enhanced 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 DRN 5-HT modulation creates a phasic response in the CeA-BNST circuit by moderating the timing of responses relative to stimulus presentation.

In chapter 3, synchronized behavioral assessments and in vivo recordings were combined with modulation of CeA- and BNST-projecting DRN 5-HT neurons, alongside pharmacological manipulation of 5-HT1A and 5-HT2A receptors during valence presentation tasks. Our results suggest that distinct DRN 5-HT projections play different roles in coding valence. The DRN5-HT-CeA pathway appears to dynamically suppress valence discrimination via 5-HT1A receptor signaling. Conversely, the DRN5-HT-BNST pathway seems to provide a critical serotonergic input that preserves discriminative coding in the CeA. Silencing this input abolishes both neural and behavioral discrimination, with selective receptor activation insufficient to rescue these processes.

Date

8-24-2026

Committee Chair

Ogundele, Olalekan M.

LSU Acknowledgement

1

LSU Accessibility Acknowledgment

1

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