Feedforward Inhibition Mediated by Preoptic Area Parvalbumin Neurons Contributes to Orexin-Induced Active Arousal from Anesthesia
6 affiliations
- 1Department of Anesthesiology, The Fourth Medical Center, PLA General Hospital, Beijing, China .
- 2Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China .
- 3Key Laboratory of Anesthesiology (The Fourth Military Medical University), Ministry of Education, Xi’an, Shaanxi, China .
- 4Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, China .
- 5Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China .
- 6Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China .
Abstract
The orexinergic system can actively promote arousal from general anesthesia, but the downstream circuit mechanisms that mediate this effect remain poorly defined. Orexin neurons densely innervate the sleep-promoting preoptic area (POA) of the hypothalamus, yet whether and how the POA contributes to orexin-induced arousal from general anesthesia is unknown. Using fiber photometry, optogenetics, neuropharmacology, and in vitro and in vivo electrophysiology in mice, we examined the orexin-to-POA circuit during isoflurane anesthesia and arousal process. We found that orexinergic inputs to the POA are suppressed by isoflurane anesthesia and recover before behavioral arousal. Enhancing POA orexinergic afferents markedly accelerated both behavioral and electrocorticographic arousal. This effect was mediated specifically by orexin type-1 receptors because local blockade of these receptors within the POA attenuated the arousal response. In situ hybridization and in vitro electrophysiology further implicated POA GABAergic neurons in this process. In vivo recordings revealed heterogeneous firing responses among POA GABAergic neurons, with excitation of a subset of parvalbumin-positive neurons preceding suppression of other GABAergic neurons, consistent with a feedforward inhibitory process contributing to orexin-induced arousal. These findings define a specific circuit mechanism for the transition from anesthesia to consciousness and suggest that parvalbumin neuron-associated feedforward inhibition within the POA mediates orexin-induced active arousal.
Related
- Reduced inhibition of hippocampal adult-born granule cells by parvalbumin interneurons after TBI
- Hippocampal CA3 connectomics reveals a gradient of mossy fiber inputs and selective feedforward inhibition onto pyramidal cells
- Notch-independent Her6 contributes to control of neural stem cell maintenance by shifting Notch signaling from lateral inhibition towards lateral induction mode
- Phase Separation Contributes to Pathogenicity for Nonsense Mediated Decay-Escaping Variant Alleles
- Local proximal tubule complement contributes to maladaptive repair in rhabdomyolysis-induced acute kidney injury and escapes systemic inhibition
BibTeX
@article{ran2026feedforward,
title = {{Feedforward Inhibition Mediated by Preoptic Area Parvalbumin Neurons Contributes to Orexin-Induced Active Arousal from Anesthesia}},
author = {Mingzi Ran and Rui Li and Haopeng Zhang and Huiming Li and Yuting He and Jing Zhen and Juan Guo and Guangchao Zhao and Mengmeng Li and Min Cai and Jiannan Li},
journal = {Research},
year = {2026},
month = nov,
doi = {10.34133/research.1474},
url = {https://doi.org/10.34133/research.1474},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Feedforward Inhibition Mediated by Preoptic Area Parvalbumin Neurons Contributes to Orexin-Induced Active Arousal from Anesthesia
AU - Mingzi Ran
AU - Rui Li
AU - Haopeng Zhang
AU - Huiming Li
AU - Yuting He
AU - Jing Zhen
AU - Juan Guo
AU - Guangchao Zhao
AU - Mengmeng Li
AU - Min Cai
AU - Jiannan Li
PY - 2026
DA - 2026/11/05
JO - Research
DO - 10.34133/research.1474
UR - https://doi.org/10.34133/research.1474
AB - The orexinergic system can actively promote arousal from general anesthesia, but the downstream circuit mechanisms that mediate this effect remain poorly defined. Orexin neurons densely innervate the sleep-promoting preoptic area (POA) of the hypothalamus, yet whether and how the POA contributes to orexin-induced arousal from general anesthesia is unknown. Using fiber photometry, optogenetics, neuropharmacology, and in vitro and in vivo electrophysiology in mice, we examined the orexin-to-POA circuit during isoflurane anesthesia and arousal process. We found that orexinergic inputs to the POA are suppressed by isoflurane anesthesia and recover before behavioral arousal. Enhancing POA orexinergic afferents markedly accelerated both behavioral and electrocorticographic arousal. This effect was mediated specifically by orexin type-1 receptors because local blockade of these receptors within the POA attenuated the arousal response. In situ hybridization and in vitro electrophysiology further implicated POA GABAergic neurons in this process. In vivo recordings revealed heterogeneous firing responses among POA GABAergic neurons, with excitation of a subset of parvalbumin-positive neurons preceding suppression of other GABAergic neurons, consistent with a feedforward inhibitory process contributing to orexin-induced arousal. These findings define a specific circuit mechanism for the transition from anesthesia to consciousness and suggest that parvalbumin neuron-associated feedforward inhibition within the POA mediates orexin-induced active arousal.
SN - 2639-5274
ER -