Topographically organized dorsal raphe activity modulates forebrain sensory-motor representations and contributes to defensive behaviors
4 affiliations
- 1Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Olav Kyrres gata 9, Trondheim, Norway
- 2National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK
- 3Kavli Institute for Systems Neuroscience and Centre for Neural Computation, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Olav Kyrres gata 9, Trondheim, Norway. [email protected]
- 4Koç University Research Center for Translational Medicine, Koç University School of Medicine, Istanbul, Turkey. [email protected]
Abstract
The dorsal raphe nucleus (DRN) plays an important role in shaping a wide range of behaviors, including mood, motivation, appetite, sleep, and social interactions. Reflecting these diverse roles, the DRN is composed of molecularly distinct and topographically organized groups of neurons that target specific regions of the forebrain. Despite these insights, fundamental questions remain regarding how DRN neurons process sensory information, what do DRN communicate to forebrain, and the role of DRN inputs in forebrain computations and animal behavior. To address these questions, we investigated the spatiotemporal activity patterns of DRN neurons, along with DRN axons and their targets in the juvenile zebrafish forebrain. Our findings revealed a remarkable topographic organization of ongoing activity and sensory-motor responses within the DRN. We discovered that a large fraction of DRN neurons are primarily driven by animals’ locomotor activity. We also observed that an anterior group of DRN neurons, marked by Gad1, exhibited distinct activity patterns during rest, locomotor activity and sensory stimulation. DRN axons broadly innervating the forebrain exhibit topographically organized excitation and inhibition in response to sensory stimulation and motor activity. Notably, we observed significant and rapid covariation between the activity of DRN axons and nearby forebrain neurons. Chemogenetic ablation of the DRN led to a marked reduction in the synchrony and sensory-motor responses across forebrain neurons, accompanied by significant deficits in adaptive behaviors. Collectively, our findings revealed the functional diversity of DRN neurons and their role in transmitting sensory and locomotor signals via topographically organized projections, which can regulate forebrain activity and play a crucial role in modulating animal behavior.
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BibTeX
@article{mutlu2026topographically,
title = {{Topographically organized dorsal raphe activity modulates forebrain sensory-motor representations and contributes to defensive behaviors}},
author = {Aytac Kadir Mutlu and Bram Serneels and Christoph Wiest and Anh‐Tuan Trinh and Ricarda Bardenhewer and Fabrizio Palumbo and Oda Bjornevik Frisvold and Inger Kristine Fjeldskaar Aukrust and Anna Maria Ostenrath and Emre Yaksi},
journal = {Nature Communications},
year = {2026},
month = jul,
doi = {10.1038/s41467-026-75490-y},
url = {https://doi.org/10.1038/s41467-026-75490-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Topographically organized dorsal raphe activity modulates forebrain sensory-motor representations and contributes to defensive behaviors
AU - Aytac Kadir Mutlu
AU - Bram Serneels
AU - Christoph Wiest
AU - Anh‐Tuan Trinh
AU - Ricarda Bardenhewer
AU - Fabrizio Palumbo
AU - Oda Bjornevik Frisvold
AU - Inger Kristine Fjeldskaar Aukrust
AU - Anna Maria Ostenrath
AU - Emre Yaksi
PY - 2026
DA - 2026/07/16
JO - Nature Communications
DO - 10.1038/s41467-026-75490-y
UR - https://doi.org/10.1038/s41467-026-75490-y
AB - The dorsal raphe nucleus (DRN) plays an important role in shaping a wide range of behaviors, including mood, motivation, appetite, sleep, and social interactions. Reflecting these diverse roles, the DRN is composed of molecularly distinct and topographically organized groups of neurons that target specific regions of the forebrain. Despite these insights, fundamental questions remain regarding how DRN neurons process sensory information, what do DRN communicate to forebrain, and the role of DRN inputs in forebrain computations and animal behavior. To address these questions, we investigated the spatiotemporal activity patterns of DRN neurons, along with DRN axons and their targets in the juvenile zebrafish forebrain. Our findings revealed a remarkable topographic organization of ongoing activity and sensory-motor responses within the DRN. We discovered that a large fraction of DRN neurons are primarily driven by animals’ locomotor activity. We also observed that an anterior group of DRN neurons, marked by Gad1, exhibited distinct activity patterns during rest, locomotor activity and sensory stimulation. DRN axons broadly innervating the forebrain exhibit topographically organized excitation and inhibition in response to sensory stimulation and motor activity. Notably, we observed significant and rapid covariation between the activity of DRN axons and nearby forebrain neurons. Chemogenetic ablation of the DRN led to a marked reduction in the synchrony and sensory-motor responses across forebrain neurons, accompanied by significant deficits in adaptive behaviors. Collectively, our findings revealed the functional diversity of DRN neurons and their role in transmitting sensory and locomotor signals via topographically organized projections, which can regulate forebrain activity and play a crucial role in modulating animal behavior.
SN - 2041-1723
ER -