Evidence map›Paper›PMID 41443375›Full record

ArticleNeurobiology of disease2026

Astrocytic GABA controls fidelity of temporal cortical processing in Fragile X Syndrome.

Victoria A Wagner, Ritika Thapa, Anna O Norman, Alexandra Varallo, Jordan Wimberly, Maham Rais, Dmytro Gerasymchuk, Timo P Piepponen, Khaleel A Razak, Maija L Castren and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurobiology of disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Victoria A WagnerNeuroscience Graduate Program, University of California Riverside, Riverside, CA, USA; Division of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Ritika ThapaNeuroscience Graduate Program, University of California Riverside, Riverside, CA, USA; Division of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Anna O NormanDivision of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Alexandra VaralloDivision of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Jordan WimberlyDivision of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Maham RaisDivision of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA.
Dmytro GerasymchukDepartment of Physiology, Medical Faculty, and Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.
Timo P PiepponenDepartment of Physiology, Medical Faculty, and Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.
Khaleel A RazakNeuroscience Graduate Program, University of California Riverside, Riverside, CA, USA; Department of Psychology, University of California Riverside, Riverside, CA, USA.
Maija L CastrenDepartment of Physiology, Medical Faculty, and Division of Pharmacology and Pharmacotherapy, University of Helsinki, Helsinki, Finland.
Iryna M EthellNeuroscience Graduate Program, University of California Riverside, Riverside, CA, USA; Division of Biomedical Sciences and Biomedical Sciences Graduate Program, School of Medicine, University of California Riverside, Riverside, CA 92521, USA. Electronic address: iryna.ethell@medsch.ucr.edu.

Funding

UC Riverside MARC U* Star Undergraduate Research ProgramT34GM062756 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MARTINEZ, ERNEST · 2001 to 2022
$8.7M
Molecular and cellular mechanisms of inhibitory synapse developmentR01NS129555 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Iryna M Ethell · 2024 to 2026
$1.4M
Cellular and molecular mechanisms of auditory processing deficits in a mouse model of Fragile X SyndromeF31NS117178 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI RAIS, MAHAM · 2020 to 2021
$56k
FRAXA Research FoundationNIGMS NIH HHS T34 GM062756NINDS NIH HHS F31 NS117178NINDS NIH HHS R01 NS129555
6 · The paper itself

Abstract

Astrocytes control neural communications by influencing GABAergic transmission through uptake and synthesis of GABA. Impaired GABAergic signaling is thought to underlie cortical hyperexcitability in autism. Here we show that dysregulation of astrocyte GABA transport in Fragile X syndrome (FXS), a leading genetic cause of autism, contributes to circuit hyperexcitability. Human FXS astrocytes derived from patient-specific induced pluripotent stem cells and mouse Fmr1 knockout (KO) astrocytes display a significant increase in levels of GABA and GABA-synthesizing enzyme GAD65/67. Our astrocyte-specific Fmr1 KO (cKO) mouse model reveals reduced inhibitory connectivity and impaired cortical responses to sound. Abnormal GABA transport in cortical astrocytes contributes to impaired fidelity of temporal processing and abnormal behaviors in cKO mice. Blocking astrocyte GABA transport enables higher PV expression, improves EEG responses to frequency-modulated sound, and corrects aberrant exploratory behavior. Our findings suggest astrocyte GABA transport plays a key role in regulating cortical inhibition, and contributes to autism-associated phenotypes.

Indexed as

AstrocytesFragile X Syndromegamma-Aminobutyric AcidTemporal LobeAnimalsDisease Models, AnimalFragile X Messenger Ribonucleoprotein 1HumansMaleMiceMice, KnockoutFmr1 protein, mouseFragile X Messenger Ribonucleoprotein 1gamma-Aminobutyric AcidAstrocytesAutismCortical circuitsElectrocortical activityFragile X SyndromeGABA transportNeurodevelopmental disordersParvalbumin inhibitory interneurons

Identifiers

PMID41443375
PMCPMC13371466

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.