{
  "abstract": "Homeostatic synaptic downscaling is a compensatory form of synaptic plasticity that stabilizes neuronal activity in response to sustained synaptic potentiation. Here, we investigated the involvement of Toll-like receptor (TLR) signaling in synaptic downscaling induced by bicuculline, a GABAA receptor antagonist. In cultured hippocampal neurons, bicuculline altered mitochondrial morphology and reduced the colocalization of TLR9 with mitochondrial DNA, an endogenous TLR9 ligand. Pharmacological inhibition of TLR9 mimicked bicuculline-induced reductions in surface expression of the AMPA receptor subunit GluA1 (sGluA1), and co-application of bicuculline and TLR9 inhibitors produced no additive effect, suggesting a shared pathway. Inhibition of SARM1, a downstream effector of TLR9, prevented bicuculline-induced sGluA1 reduction. Bicuculline also upregulated another upstream effector of SARM1, TLR7, which is negatively regulated by TLR9. TLR7 inhibition blocked, whereas TLR7 activation mimicked, bicuculline-induced decreases in sGluA1. These findings indicate that the shift from TLR9 to TLR7 signaling contributes to homeostatic synaptic downscaling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Engineering Science, Graduate School of Informatics and Engineering, The University of Electro-Communications, Tokyo, 182-8585, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Akira Koga"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuhei Kishi"
    },
    {
      "affs": [
        0
      ],
      "name": "Shinji Matsuda"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7j7895zffn79v.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jphyss.2026.100112",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718798/?tool=EBI",
  "id": "7j7895zffn79v",
  "issns": [
    "1880-6546",
    "1880-6562"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13718798",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7222932440",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13718798/pdf/?tool=EBI",
  "pmcid": "PMC13718798",
  "pmid": "42913314",
  "published": "2026-10-19",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/7j7895zffn79v.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:38Z",
      "native_id": "PMC:PMC13718798",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13718798"
    },
    {
      "first_seen": "2026-11-02T12:22:45Z",
      "native_id": "PMC13718798",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jphyss.2026.100112"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "Toll-like receptor signaling modulates AMPA receptor trafficking in homeostatic synaptic downscaling",
  "title_text": "Toll-like receptor signaling modulates AMPA receptor trafficking in homeostatic synaptic downscaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:45Z",
  "url": "https://research.draconitic.com/paper/7j7895zffn79v",
  "venue": "The journal of physiological sciences : JPS",
  "versions": []
}