Topographically organized dorsal raphe activity modulates forebrain sensory-motor representations and contributes to defensive behaviors

The dorsal raphe nucleus (DRN) shapes behaviors including mood and motivation. The DRN contains molecularly distinct and topographically organized neurons that target specific forebrain regions. To understand how DRN neurons process sensory information, we investigated the spatiotemporal activity patterns of DRN neurons, DRN axons, and their forebrain targets in zebrafish. We found a remarkable topographic organization of ongoing activity and sensory-motor responses within the DRN. A subset of DRN neurons was driven by locomotion and sensory stimuli. Gad1-positive DRN neurons exhibited distinct activity during rest and sensory-motor stimulation. DRN axons in the forebrain showed topographically organized excitation and inhibition in response to sensory stimulation and locomotion. DRN axons covaried with forebrain neuronal activity. DRN ablation reduced the synchrony and sensory-motor responses of forebrain neurons and enhanced defensive behaviors. We revealed the functional diversity of DRN neurons and their role in transmitting sensory and locomotor signals via topographically organized forebrain projections.