Serotonergic neurons in the dorsal raphe nucleus scale O2 utilization in response to traumatic stress

Zhu, X.-h.; Zhang, Y.; Pan, Y.-d.; Zheng, W.-y.; Wen, Q.-q.; Zhu, M.-z.; Li, H.-y.; Liang, W.-q.; Zhu, Z.-y.; Liu, B.-c.; Yuan, X.-r.; Wu, Y.; Dong, J.-h.; Davoli, M. A.; Turecki, G.; Mechawar, N.

doi:10.64898/2026.01.14.699586

bioRxiv · 10.64898/2026.01.14.699586

Serotonergic neurons in the dorsal raphe nucleus scale O2 utilization in response to traumatic stress

Zhu, X.-h.·Zhang, Y.·Pan, Y.-d.·Zheng, W.-y.·Wen, Q.-q.·Zhu, M.-z.·Li, H.-y.·Liang, W.-q.·Zhu, Z.-y.·Liu, B.-c.·Yuan, X.-r.·Wu, Y.·Dong, J.-h.·Davoli, M. A.·Turecki, G.·Mechawar, N.

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Abstract

Trauma is a main cause of psychiatric disorders. Approximately 24% of trauma-exposed individuals suffer from posttraumatic stress disorder throughout their lifetime, however, the vast majority of people are resilient. Why some people are resilient while others develop mental disorders in face of trauma in a short timescale? Here, we show that O2 actively initiates a cell-signaling pathway that regulates behavioral outcomes in response to traumatic stress. We found that serotonergic neurons in the dorsal raphe nucleus (DRN5-HT neurons) projecting to the ventral caudate putamen and the ventral tegmental area exhibit distinct physiological patterns of O2 utilization. In response to traumatic stress, O2 utilization in these neurons changed individually, following either a susceptible or resilient pattern, thereby modulating corresponding behaviors. This O2 scaling was regulated by ferroptosis within the DRN5-HT neurons. Thus, we identify a previously unrecognized function of O2, opening an avenue for the treatment and prevention of stress-related disorders.

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Zhu, X.-h., Zhang, Y., Pan, Y.-d., Zheng, W.-y., Wen, Q.-q., Zhu, M.-z., Li, H.-y., Liang, W.-q., Zhu, Z.-y., Liu, B.-c., Yuan, X.-r., Wu, Y., Dong, J.-h., Davoli, M. A., Turecki, G., Mechawar, N.. 2026-01-15. Serotonergic neurons in the dorsal raphe nucleus scale O2 utilization in response to traumatic stress. https://doi.org/10.64898/2026.01.14.699586

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