ArticleProceedings of the National Academy of Sciences of the United States of America2015
Compromising the phosphodependent regulation of the GABAAR β3 subunit reproduces the core phenotypes of autism spectrum disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Motor cortex excitability and inhibitory imbalance in autism spectrum disorder assessed with transcranial magnetic stimulation: a systematic review.Translational psychiatry · 2019Pooled it
- Early postnatal exposure to bicuculline modulates E/I balance and induces ASD-like behavioral phenotypes in mice.Animal cells and systems · 2025Article
- Pleiotropic neurotransmitters: neurotransmitter-receptor crosstalk regulates excitation-inhibition balance in social brain functions and pathologies.Frontiers in neuroscience · 2025Review
- Spontaneous Calcium Transients Recorded from Striatal Astrocytes in a Preclinical Model of Autism.Neurochemical research · 2024Article
- The PDE4 inhibitor apremilast modulates ethanol responses in Gabrb1-S409A knock-in mice via PKA-dependent and independent mechanisms.Neuropharmacology · 2024Article
- VHH Nanobody Versatility against Pentameric Ligand-Gated Ion Channels.Journal of medicinal chemistry · 2024Review
- Selective PDE4B and PDE4D inhibitors produce distinct behavioral responses to ethanol and GABAergic drugs in mice.Neuropharmacology · 2023Article
- Apremilast-induced increases in acute ethanol intoxication and decreases in ethanol drinking in mice involve PKA phosphorylation of GABANeuropharmacology · 2022Article
- Generational synaptic functions of GABAJournal of biomedical science · 2022Article
- FMRP regulates GABACell reports · 2022Article
- Analyzing the mechanisms that facilitate the subtype-specific assembly ofFrontiers in molecular neuroscience · 2022Article
- Preventing Phosphorylation of the GABAFrontiers in molecular neuroscience · 2022Article
- Channelopathies in fragile X syndrome.Nature reviews. Neuroscience · 2021Review
- A critical residue in the αeLife · 2021Article
- Overlaps, gaps, and complexities of mouse models of Developmental and Epileptic Encephalopathy.Neurobiology of disease · 2021Review
- Genetic Code Expansion and Click-Chemistry Labeling to Visualize GABA-A Receptors by Super-Resolution Microscopy.Frontiers in synaptic neuroscience · 2021Article
- GABAergic System Dysfunction in Autism Spectrum Disorders.Frontiers in cell and developmental biology · 2021Review
- Metabotropic, but not allosteric, effects of neurosteroids on GABAergic inhibition depend on the phosphorylation of GABAThe Journal of biological chemistry · 2019Article
- Identification of a Core Amino Acid Motif within the α Subunit of GABACell reports · 2019Article
- Targeting GABAFrontiers in molecular neuroscience · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Alterations in the efficacy of neuronal inhibition mediated by GABAA receptors (GABAARs) containing β3 subunits are continually implicated in autism spectrum disorders (ASDs). In vitro, the plasma membrane stability of GABAARs is potentiated via phosphorylation of serine residues 408 and 409 (S408/9) in the β3 subunit, an effect that is mimicked by their mutation to alanines. To assess if modifications in β3 subunit expression contribute to ASDs, we have created a mouse in which S408/9 have been mutated to alanines (S408/9A). S408/9A homozygotes exhibited increased phasic, but decreased tonic, inhibition, events that correlated with alterations in the membrane stability and synaptic accumulation of the receptor subtypes that mediate these distinct forms of inhibition. S408/9A mice exhibited alterations in dendritic spine structure, increased repetitive behavior, and decreased social interaction, hallmarks of ASDs. ASDs are frequently comorbid with epilepsy, and consistent with this comorbidity, S408/9A mice exhibited a marked increase in sensitivity to seizures induced by the convulsant kainic acid. To assess the relevance of our studies using S408/9A mice for the pathophysiology of ASDs, we measured S408/9 phosphorylation in Fmr1 KO mice, a model of fragile X syndrome, the most common monogenetic cause of ASDs. Phosphorylation of S408/9 was selectively and significantly enhanced in Fmr1 KO mice. Collectively, our results suggest that alterations in phosphorylation and/or activity of β3-containing GABAARs may directly contribute to the pathophysiology of ASDs.
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Registered trials
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.