{
  "abstract": "Electrical signaling across distinct populations of brain cells underpins cognitive and emotional function; however, approaches that selectively regulate electrical signaling between two cellular components of a mammalian neural circuit remain sparse. Here, we engineered an electrical synapse composed of two connexin proteins found in Morone americana (white perch fish) – connexin34.7 and connexin35 – to accomplish mammalian circuit modulation. By exploiting protein mutagenesis, devising a new in vitro system for assaying connexin hemichannel docking, and performing computational modeling of hemichannel interactions, we uncovered a structural motif that contributes to electrical synapse formation. Targeting these motifs, we designed connexin34.7 and connexin35 hemichannels that dock with each other to form an electrical synapse, but not with other major connexins expressed in the mammalian central nervous system. We validated this electrical synapse in vivo using C. elegans and mice, demonstrating that it can strengthen communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish ‘ L ong-term in tegration of C ircuits using conne x ins’ (LinCx) for precision circuit-editing in mammals.",
  "abstract_shown": true,
  "affiliations": [
    "Deparment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA",
    "Howard Hughes Medical Institute, Chevy Chase, MD, USA",
    "Department of Neurobiology, Duke University Medical Center, Durham, NC, USA",
    "Department of Neuroscience and Department of Cell Biology, Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT, USA",
    "Department of Biomedical Engineering, Duke University, Durham, NC, USA",
    "Salk Institute for Biological Studies, La Jolla, CA, USA",
    "Department of Neuroscience, University of Connecticut School of Medicine, Farmington, CT, USA",
    "Instituto de Neurobiología, Recinto de Ciencias Médicas, Universidad de Puerto Rico, San Juan, Puerto Rico",
    "Department of Molecular Physiology and Biophysics, Department of Psychiatry, University of Iowa, Iowa City, IA, USA",
    "Deparment of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. kafui.dzirasa@duke.edu",
    "Department of Biomedical Engineering, Duke University, Durham, NC, USA. kafui.dzirasa@duke.edu",
    "Department of Neurobiology, Duke University Medical Center, Durham, NC, USA. kafui.dzirasa@duke.edu",
    "Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. kafui.dzirasa@duke.edu",
    "Howard Hughes Medical Institute, Chevy Chase, MD, USA. kafui.dzirasa@duke.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Elizabeth Ransey",
      "orcid": "0000-0002-8118-466X"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Gwenaëlle E. Thomas"
    },
    {
      "affs": [
        3
      ],
      "name": "Elias M. Wisdom",
      "orcid": "0000-0002-7549-4127"
    },
    {
      "affs": [
        3
      ],
      "name": "Agustin Almoril-Porras",
      "orcid": "0000-0002-6949-6783"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryan Bowman"
    },
    {
      "affs": [
        4,
        1
      ],
      "name": "Elise Adamson"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kathryn K. Walder-Christensen",
      "orcid": "0000-0001-6757-0698"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Jesse A White"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Dalton N. Hughes",
      "orcid": "0000-0001-6227-5497"
    },
    {
      "affs": [
        0
      ],
      "name": "Hannah T. Schwennesen",
      "orcid": "0000-0003-2410-7630"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Caly Ferguson"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Kay M. Tye",
      "orcid": "0000-0002-2435-0182"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Stephen D. Mague"
    },
    {
      "affs": [
        6
      ],
      "name": "Longgang Niu",
      "orcid": "0000-0001-7209-7436"
    },
    {
      "affs": [
        6
      ],
      "name": "Zhao‐Wen Wang",
      "orcid": "0000-0003-3574-8556"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Daniel Colón-Ramos",
      "orcid": "0000-0003-0223-7717"
    },
    {
      "affs": [
        8
      ],
      "name": "Rainbo C. Hultman",
      "orcid": "0000-0002-6232-7602"
    },
    {
      "affs": [
        4
      ],
      "name": "Nenad Bursac",
      "orcid": "0000-0002-5688-6061"
    },
    {
      "affs": [
        9,
        10,
        11,
        12,
        13
      ],
      "name": "Kafui Dzirasa",
      "orcid": "0000-0003-4280-9994"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/05t362mz8dvzv.bib",
  "cited_by": 6,
  "doi": "10.1038/s41586-026-10501-y",
  "fulltext_url": null,
  "id": "05t362mz8dvzv",
  "issns": [
    "0028-0836",
    "1476-4687"
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  "landing_url": "https://doi.org/10.1038/s41586-026-10501-y",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "openalex",
      "1312|Connexins and lens biology"
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  "pdf_url": null,
  "pmcid": "PMC11974911",
  "pmid": "40196531",
  "published": "2026-05-13",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/05t362mz8dvzv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
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      "url": "https://doi.org/10.1038/s41586-026-10501-y"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Connexins and lens biology",
      "subfield": "molecular-biology"
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  ],
  "title": "Long-term editing of brain circuits using an engineered electrical synapse",
  "title_text": "Long-term editing of brain circuits using an engineered electrical synapse",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T13:20:30Z",
  "url": "https://research.draconitic.com/paper/05t362mz8dvzv",
  "venue": "Nature",
  "versions": []
}