TOPOGRAPHICALLY STRUCTURED DORSAL RAPHE ACTIVITY COORDINATES FOREBRAIN DYNAMICS AND DEFENSIVE BEHAVIORS

The dorsal raphe nucleus (DRN) is essential for shaping diverse behaviors, including mood, motivation, appetite, sleep, and social interactions. Consistent with these broad functions, the DRN is composed of molecularly distinct and topographically organized neuronal populations that project to specific regions of the forebrain. Despite this organizational complexity, fundamental questions remain about how DRN neurons process sensory information, what signals they convey to the forebrain, and how these inputs influence forebrain computations and behavior. To address these questions, we examined the spatiotemporal activity patterns of DRN neurons, their axonal projections, and their target regions in the juvenile zebrafish forebrain. We found a striking topographic organization of ongoing activity and sensory–motor responses within the DRN. A subset of DRN neurons was strongly driven by locomotor activity, while an anterior Gad1-expressing population showed distinct activity patterns during rest, movement, and sensory stimulation. DRN axons broadly innervating the forebrain exhibited topographically organized excitation and inhibition in response to sensory inputs and motor activity. Notably, we observed rapid and robust covariation between DRN axon activity and forebrain neuronal dynamics. Chemogenetic ablation of the DRN significantly reduced synchrony and sensory–motor responsiveness across forebrain neurons, and it enhanced sustained defensive behaviors following transient sensory stimuli. Together, these findings reveal the functional diversity of DRN neurons and demonstrate that the DRN transmits sensory and locomotor signals through topographically organized projections that shape forebrain activity and regulate defensive behavior.