Orexin signalling in the nucleus accumbens promotes arousal from isoflurane anaesthesia and restores communication between the nucleus accumbens and frontal cortex.
British journal of anaesthesia May 28, 2025 Jia Huo, Huiming Li, Dan Wang et al. 4 citations
Orexin promotes arousal from general anaesthesia, but the mechanisms are unclear. The nucleus accumbens (NAc), a target of orexin neurons, helps regulate consciousness. During isoflurane anaesthesia, orexinergic afferents in the NAc were wake-active. Optogenetic activation of these terminals prolonged induction time, shortened emergence time, and reduced the burst suppression ratio from 67.4% to 14.5% during 1.4 vol% isoflurane anaesthesia. Microinjection of orexin-A into the NAc promoted arousal. Orexin-1 receptors were expressed mainly in NAc D1 receptor-positive neurons. Activation increased D1R+ neuron firing from 0.77 to 2.53 spikes per second and restored NAc-to-frontal cortex coherence. Orexin restores communication between the NAc and frontal cortex by upregulating D1R+ neuron activity, thereby promoting arousal from isoflurane anaesthesia.