{
  "abstract": "GABAergic neurons critically regulate epileptic seizures, yet circuit mechanisms mediated by subtype-specific GABAergic neurons in the zona incerta (ZI) remain unclear. Here we reveal the essential role of ZI somatostatin⁺ GABAergic neurons in seizure modulation in the mouse hippocampal kindling model. In vivo Ca²⁺ fiber photometry and optogenetics show that ZI GABAergic neurons are gradually activated during seizure progression. Opto-activation inhibits seizure progression, especially the spread of generalized seizures at the later phase, whereas opto-inhibition accelerates it. Although both somatostatin⁺ and parvalbumin⁺ neurons are dynamically recruited during seizure progression, only somatostatin⁺ neurons exert bidirectional seizure modulation. Circuitry mapping and functional modulation demonstrate that ZI somatostatin⁺ neurons projecting to the ventromedial hypothalamus (VMH) glutamatergic neurons suppress the spread of generalized seizures by inhibiting the excitability of VMH-related downstream seizure-spread regions. These findings uncover a cell-type-specific circuit mechanism for seizure regulation by ZI somatostatin⁺ neurons, highlighting these neurons as a potential therapeutic target for epilepsy.",
  "abstract_shown": true,
  "affiliations": [
    "Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.",
    "Medical Research Center, Shandong Medical and Pharmaceutical University Hospital, Binzhou, China.",
    "College of Pharmaceutical Sciences, Zhejiang Pharmaceutical University, Ningbo, China.",
    "Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. fei-fan@zju.edu.cn.",
    "Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. xucenglin5zz@zju.edu.cn.",
    "Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China. wang-yi@zju.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Mengdi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Zhou"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yeping Ruan"
    },
    {
      "affs": [
        0
      ],
      "name": "Dongxiao Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lilong Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajia Ying"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenjing Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianyu Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Menghan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhong Chen",
      "orcid": "0000-0003-4755-9357"
    },
    {
      "affs": [
        3
      ],
      "name": "Fan Fei"
    },
    {
      "affs": [
        4
      ],
      "name": "Cenglin Xu",
      "orcid": "0000-0002-4337-3777"
    },
    {
      "affs": [
        5
      ],
      "name": "Yi Wang",
      "orcid": "0000-0002-1350-2961"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1j2nb9r769y7z.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78174-9",
  "fulltext_url": "https://europepmc.org/articles/PMC13720055",
  "id": "1j2nb9r769y7z",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42957689",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2738|Epilepsy research and treatment"
    ]
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  "openalex": "W7214709493",
  "pdf_url": "https://europepmc.org/articles/PMC13720055?pdf=render",
  "pmcid": "PMC13720055",
  "pmid": "42957689",
  "published": "2026-09-29",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/1j2nb9r769y7z.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:44Z",
      "native_id": "MED:42957689",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42957689"
    },
    {
      "first_seen": "2026-11-02T12:23:54Z",
      "native_id": "PMC13720055",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78174-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Epilepsy research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Zona incerta somatostatin⁺ neurons modulate seizure progression through hypothalamic circuits.",
  "title_text": "Zona incerta somatostatin⁺ neurons modulate seizure progression through hypothalamic circuits.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:00Z",
  "url": "https://research.draconitic.com/paper/1j2nb9r769y7z",
  "venue": "Nature communications",
  "versions": []
}