{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology, The Fourth Medical Center, PLA General Hospital, Beijing, China .",
    "Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China .",
    "Key Laboratory of Anesthesiology (The Fourth Military Medical University), Ministry of Education, Xi’an, Shaanxi, China .",
    "Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, China .",
    "Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China .",
    "Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China ."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mingzi Ran"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Rui Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Haopeng Zhang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Huiming Li"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Yuting He"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jing Zhen"
    },
    {
      "affs": [
        1,
        2,
        4
      ],
      "name": "Juan Guo"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Guangchao Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengmeng Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Min Cai"
    },
    {
      "affs": [
        1,
        2,
        5
      ],
      "name": "Jiannan Li",
      "orcid": "0000-0002-0748-957X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dhyghyzesr36n.bib",
  "cited_by": 0,
  "doi": "10.34133/research.1474",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735207/",
  "id": "dhyghyzesr36n",
  "issns": [
    "2639-5274"
  ],
  "landing_url": "https://doi.org/10.34133/research.1474",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Health Science"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2805|Sleep and Wakefulness Research"
    ]
  ],
  "openalex": "W7222913733",
  "pdf_url": null,
  "pmcid": "PMC13735207",
  "pmid": "42990727",
  "published": "2026-11-05",
  "publisher": "AAAS Science Partner Journal Program",
  "ris": "https://research.draconitic.com/paper/dhyghyzesr36n.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:20:55Z",
      "native_id": "PMC13735207",
      "source": "pmc",
      "url": "https://doi.org/10.34133/research.1474"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2805|Sleep and Wakefulness Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Feedforward Inhibition Mediated by Preoptic Area Parvalbumin Neurons Contributes to Orexin-Induced Active Arousal from Anesthesia",
  "title_text": "Feedforward Inhibition Mediated by Preoptic Area Parvalbumin Neurons Contributes to Orexin-Induced Active Arousal from Anesthesia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:20:55Z",
  "url": "https://research.draconitic.com/paper/dhyghyzesr36n",
  "venue": "Research",
  "versions": []
}