{
  "abstract": "Background and hypothesis\n\nThe neurodevelopmental hypothesis of schizophrenia posits that early-acting genetic risk factors precipitate pathological neurodevelopmental processes that result in neural network dysfunctions during adolescence. Human gene variants of the epidermal growth factor-like ligand Neuregulin 1 (NRG1) and its tyrosine kinase receptor ErbB4 are putative risk factors in schizophrenia, and aberrant NRG1 signaling has been implicated in schizophrenia-relevant endophenotypes. However, insight into associated pathomechanisms remains limited.Study design\n\nWe modeled embryonic glutamatergic neuron-specific NRG1 type I overexpression in a conditional transgenic mouse line to investigate the impact of early hyperactive NRG1 type I signaling on neuronal network functions in the hippocampus in vivo.Study results\n\nNRG1 type I transgenic mice display abnormal gamma-frequency network oscillations in the adolescent hippocampus, in the absence of neuroinflammation or changes in hippocampal morphology. Instead, we found extra-synaptic NRG1 type I accumulation, which was associated with ErbB4 hyperphosphorylation, an increased size and number of Kv2.1 potassium channel-marked endoplasmic reticulum (ER)-plasma membrane (PM) junctions, and a reduction of A-type potassium channel currents in pyramidal cells.Conclusions\n\nTogether, these findings suggest a model in which early-onset extra-synaptic NRG1 type I accumulation at ER-PM junctions causes sustained changes in neuronal excitability, ultimately contributing to deficits in neuronal network oscillations as observed in various neuropsychiatric disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurogenetics, Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Lower Saxony, Germany.",
    "Paul Flechsig Institute, Centre for Neuropathology and Brain Research, Medical Faculty, Leipzig University, 04103 Leipzig, Saxony, Germany.",
    "Center for Research in Biotechnology (CIB), Costa Rica Institute of Technology (TEC), 30109 Cartago, Costa Rica.",
    "Department of Neurobiology, Max-Planck-Institute for Multidisciplinary Sciences, 37075 Göttingen, Lower Saxony, Germany.",
    "Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Lower Saxony, Germany.",
    "Neuroscience Research Center (CIN), University of Costa Rica (UCR), 11501-2060 San José, Costa Rica.",
    "Department of Physiology, School of Medicine, University of Costa Rica (UCR), 11501 San José, Costa Rica.",
    "National Center of Biotechnological Innovations (CENIBiot)/National Center of High Technology (CENAT), 1174-1200 San Jose, Costa Rica.",
    "Institute of Anatomy, Leipzig University, 04103 Leipzig, Saxony, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "María Clara Soto-Bernardini"
    },
    {
      "affs": [
        3
      ],
      "name": "Sua Jeong"
    },
    {
      "affs": [
        1
      ],
      "name": "Hadiseh Hosseinnia"
    },
    {
      "affs": [
        3
      ],
      "name": "Bekir Altas"
    },
    {
      "affs": [
        3
      ],
      "name": "Hong Jun Rhee"
    },
    {
      "affs": [
        3
      ],
      "name": "Chungku Lee"
    },
    {
      "affs": [
        4
      ],
      "name": "Yvonne Schill"
    },
    {
      "affs": [
        1
      ],
      "name": "Ulrike Zeitschel"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Tilmann Götze"
    },
    {
      "affs": [
        1
      ],
      "name": "Julia Hellriegel"
    },
    {
      "affs": [
        1
      ],
      "name": "Maria Lehning"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Oscar Brenes",
      "orcid": "0000-0003-3830-9364"
    },
    {
      "affs": [
        5
      ],
      "name": "Jaime Fornaguera"
    },
    {
      "affs": [
        7
      ],
      "name": "José Aníbal Mora-Villalobos"
    },
    {
      "affs": [
        8
      ],
      "name": "Robert Fledrich"
    },
    {
      "affs": [
        1
      ],
      "name": "Ruth M Stassart"
    },
    {
      "affs": [
        3
      ],
      "name": "Jeong Seop Rhee"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Markus H Schwab"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0s2shmft336ex.bib",
  "cited_by": 0,
  "doi": "10.1093/schbul/sbag168",
  "fulltext_url": "https://europepmc.org/articles/PMC13720722",
  "id": "0s2shmft336ex",
  "issns": [
    "1787-9965",
    "1745-1701",
    "0586-7614"
  ],
  "landing_url": "https://europepmc.org/article/MED/42960987",
  "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",
      "AcademicSubjects/MED00810"
    ],
    [
      "heading",
      "Regular Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://europepmc.org/articles/PMC13720722?pdf=render",
  "pmcid": "PMC13720722",
  "pmid": "42960987",
  "published": "2026-10-01",
  "publisher": "Oxford University Press",
  "ris": "https://research.draconitic.com/paper/0s2shmft336ex.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:46Z",
      "native_id": "MED:42960987",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42960987"
    },
    {
      "first_seen": "2026-11-03T12:21:33Z",
      "native_id": "PMC13720722",
      "source": "pmc",
      "url": "https://doi.org/10.1093/schbul/sbag168"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:2738|Schizophrenia research and treatment",
      "subfield": "psychiatry"
    }
  ],
  "title": "Extra-Synaptic Functions of NRG1 Type I Signaling in Hippocampal γ-Oscillations.",
  "title_text": "Extra-Synaptic Functions of NRG1 Type I Signaling in Hippocampal γ-Oscillations.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:33Z",
  "url": "https://research.draconitic.com/paper/0s2shmft336ex",
  "venue": "Schizophrenia bulletin",
  "versions": []
}