{
  "abstract": "Both phasic and tonic GABAergic activities in the cortex are shaped by the clearance of GABA from the extracellular space by GABA transporters (GATs). However, estimates of the time-course of GAT activity from GAT currents, GABAA, and GABAB electrophysiological recordings range from tens of milliseconds to multiple seconds. These estimates may reflect receptor properties rather than extracellular GABA dynamics. Understanding how long GABA is free in the extracellular space is key to understanding how inhibition controls activity but has been technically challenging. Here, we utilize the fluorescent GABA sensor, iGABASnFr, to enable us to optically assay extracellular GABA dynamics following bursts of synaptic activity. In the mouse cerebral cortex of either sex, we show that GABA rapidly disperses from release sites via diffusion, with very little role for active transport by GATs. Following diffusion from the sites of release, GABA then accumulates in the extracellular space, where GATs require hundreds of milliseconds to remove it. For areas of high-density GABA release or during bursts of activity, this clearance is further slowed. Continued GABA release and summation in the extracellular space for bursts of activity contrasts with recorded inhibitory postsynaptic current (IPSC) signals, which rapidly depress with additional stimuli, suggesting a disconnect between IPSCs and extracellular GABA. Lastly, the resulting extracellular accumulation of GABA can act heterosynaptically by activating and/or desensitizing GABAA receptors. Together, this raises new questions about how GABAergic inhibition works to shape network function and suggests a spatiotemporal continuum of extracellular GABA.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111",
    "Neuroscience Program, Tufts Graduate School of Biomedical Sciences, Boston, Massachusetts 02111",
    "Synaptic Physiology Section, NINDS Intramural Research Program, National Institutes of Health, Bethesda, Maryland 20892"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Reyna L. Gariepy"
    },
    {
      "affs": [
        0
      ],
      "name": "Jesse B. Blackman",
      "orcid": "0009-0001-1403-9577"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anushree S. Gupte"
    },
    {
      "affs": [
        2
      ],
      "name": "Jeffrey S. Diamond",
      "orcid": "0000-0002-1770-2629"
    },
    {
      "affs": [
        0
      ],
      "name": "Chris G. Dulla",
      "orcid": "0000-0002-6560-6535"
    },
    {
      "affs": [
        0
      ],
      "name": "Moritz Armbruster",
      "orcid": "0000-0003-2341-513X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4d75m80yyvhc6.bib",
  "cited_by": 0,
  "doi": "10.1523/jneurosci.0354-26.2026",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735383/",
  "id": "4d75m80yyvhc6",
  "issns": [
    "0270-6474",
    "1529-2401"
  ],
  "landing_url": "https://doi.org/10.1523/jneurosci.0354-26.2026",
  "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",
      "Cellular/Molecular"
    ],
    [
      "heading",
      "Research Articles"
    ],
    [
      "openalex",
      "2804|Neuroscience and Neuropharmacology Research"
    ]
  ],
  "openalex": "W7221783899",
  "pdf_url": "https://www.jneurosci.org/content/jneuro/early/2026/10/12/JNEUROSCI.0354-26.2026.full.pdf",
  "pmcid": "PMC13735383",
  "pmid": "42875181",
  "published": "2026-10-14",
  "publisher": "Society for Neuroscience",
  "ris": "https://research.draconitic.com/paper/4d75m80yyvhc6.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:04Z",
      "native_id": "PMC13735383",
      "source": "pmc",
      "url": "https://doi.org/10.1523/jneurosci.0354-26.2026"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Neuroscience and Neuropharmacology Research",
      "subfield": "neuroscience"
    }
  ],
  "title": "iGABASnFr Imaging Reveals that GABA Clearance Is Rapidly Overwhelmed in the Cerebral Cortex",
  "title_text": "iGABASnFr Imaging Reveals that GABA Clearance Is Rapidly Overwhelmed in the Cerebral Cortex",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:04Z",
  "url": "https://research.draconitic.com/paper/4d75m80yyvhc6",
  "venue": "The Journal of Neuroscience",
  "versions": []
}