ArticleThe Journal of biological chemistry2013
Altered cortical GABAA receptor composition, physiology, and endocytosis in a mouse model of a human genetic absence epilepsy syndrome.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 58 citations in OpenAlex.
- GABASynapse (New York, N.Y.) · 2026Review
- Role of hippocampus in epileptogenesis: new insights in the cross-talks between the underlying mechanisms.Acta neurologica Belgica · 2025Review
- Molecular Mechanisms Underlying the Generation of Absence Seizures: Identification of Potential Targets for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.Brain : a journal of neurology · 2024Article
- Altered GABAInternational journal of molecular sciences · 2022Article
- Metabolic modulation of synaptic failure and thalamocortical hypersynchronization with preserved consciousness in Glut1 deficiency.Science translational medicine · 2022Article
- GABA facilitates spike propagation through branch points of sensory axons in the spinal cord.Nature neuroscience · 2022Article
- Article
- GABAInternational journal of molecular sciences · 2022Article
- Artificial sleep-like up/down-states induce synaptic plasticity in cortical neurons from mouse brain slices.Frontiers in cellular neuroscience · 2022Article
- Hippocampal cAMP regulates HCN channel function on two time scales with differential effects on animal behavior.Science translational medicine · 2021Article
- Dysregulation of GABAA Receptor-Mediated Neurotransmission during the Auditory Cortex Critical Period in the Fragile X Syndrome Mouse Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Exercise Improved the Anti-Epileptic Effect of Carbamazepine through GABA Enhancement in Epileptic Rats.Neurochemical research · 2021Article
- Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Impaired State-Dependent Potentiation of GABAergic Synaptic Currents Triggers Seizures in a Genetic Generalized Epilepsy Model.Cerebral cortex (New York, N.Y. : 1991) · 2021Article
- Selective loss of the GABAJournal of neurophysiology · 2020Article
- Prevention of premature death and seizures in a Depdc5 mouse epilepsy model through inhibition of mTORC1.Human molecular genetics · 2020Article
- An expanded parenchymal CD8+ T cell clone in GABAAnnals of clinical and translational neurology · 2020Article
- The functional microscopic neuroanatomy of the human subthalamic nucleus.Brain structure & function · 2019Article
- Current Opinions and Consensus for Studying Tremor in Animal Models.Cerebellum (London, England) · 2019Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Patients with generalized epilepsy exhibit cerebral cortical disinhibition. Likewise, mutations in the inhibitory ligand-gated ion channels, GABAA receptors (GABAARs), cause generalized epilepsy syndromes in humans. Recently, we demonstrated that heterozygous knock-out (Hetα1KO) of the human epilepsy gene, the GABAAR α1 subunit, produced absence epilepsy in mice. Here, we determined the effects of Hetα1KO on the expression and physiology of GABAARs in the mouse cortex. We found that Hetα1KO caused modest reductions in the total and surface expression of the β2 subunit but did not alter β1 or β3 subunit expression, results consistent with a small reduction of GABAARs. Cortices partially compensated for Hetα1KO by increasing the fraction of residual α1 subunit on the cell surface and by increasing total and surface expression of α3, but not α2, subunits. Co-immunoprecipitation experiments revealed that Hetα1KO increased the fraction of α1 subunits, and decreased the fraction of α3 subunits, that associated in hybrid α1α3βγ receptors. Patch clamp electrophysiology studies showed that Hetα1KO layer VI cortical neurons exhibited reduced inhibitory postsynaptic current peak amplitudes, prolonged current rise and decay times, and altered responses to benzodiazepine agonists. Finally, application of inhibitors of dynamin-mediated endocytosis revealed that Hetα1KO reduced base-line GABAAR endocytosis, an effect that probably contributes to the observed changes in GABAAR expression. These findings demonstrate that Hetα1KO exerts two principle disinhibitory effects on cortical GABAAR-mediated inhibitory neurotransmission: 1) a modest reduction of GABAAR number and 2) a partial compensation with GABAAR isoforms that possess physiological properties different from those of the otherwise predominant α1βγ GABAARs.
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