The Serotonergic Dorsal Raphe Promotes Emergence from Propofol Anesthesia in Zebrafish

• DOI: 10.1523/jneurosci.2125-23.2025
• Publication Date: 2025-02-13T18:50:30Z
• Authors: Xiaoxuan Yang; Shan Zhu; Miaoyun Xia; Le Sun; Sha Li; Peishan Xiang; Funing Li; Qiusui Deng; Lijun Chen; Wei Zhang; Ying Wang; Qiang Li; Zhuochen Lyu; Xufei Du; Jiulin Du; Qianzi Yang; Yan Luo
• Keywords: Dorsal raphe nucleus; Premovement neuronal activity

The mechanisms through which general anesthetics induce loss of consciousness remain unclear. Previous studies have suggested that dorsal raphe nucleus serotonergic (DRN 5-HT ) neurons are involved in inhalational anesthesia, but the underlying neuronal and synaptic not well understood. In this study, we investigated role DRN propofol-induced anesthesia larval zebrafish (sex undetermined at developmental stage) using a combination vivo single-cell calcium imaging, two-photon laser ablation, optogenetic activation, glutamate imaging whole-cell recording. We found activity reversibly decreased during propofol perfusion. Ablation prolonged emergence from 30 μM while induction times were affected under concentrations 1 μM, 3 μM. Additionally, activation strongly promoted anesthesia. Propofol application to suppressed both spontaneous current injection-evoked spike firing, abolished excitatory postsynaptic currents, membrane input resistance. Presynaptic release events also by propofol. Furthermore, hyperpolarization caused was picrotoxin, GABA A receptor antagonist, shortened time when locally applied DRN. Our results reveal inhibiting presynaptic inputs inducing receptor-mediated hyperpolarization. Significance Statement neural studied zebrafish, employing single-neuron resolution, induction. suppresses via receptors blocking inputs. These findings further support as an ideal model for investigating