ArticleBiological psychiatry2016
Bidirectional Homeostatic Regulation of a Depression-Related Brain State by Gamma-Aminobutyric Acidergic Deficits and Ketamine Treatment.
Article in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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Who cites it
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Dissociation of Golgi-associated DHHC-type Zinc Finger Protein (GODZ)- and Sertoli Cell Gene with a Zinc Finger Domain-β (SERZ-β)-mediated Palmitoylation by Loss of Function Analyses in Knock-out Mice.The Journal of biological chemistry · 2016Guideline
- Magnetoencephalographic Correlates of Suicidal Ideation in Major Depression.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2020Trial
- Transcriptome changes of disinhibited somatostatin neurons in the medial prefrontal cortex mediating male-specific stress resilience.Research square · 2026Article
- Ketamine and Evolving Neuroplasticity.Clinical drug investigation · 2026Review
- A Comparison of Positive and Negative Allosteric Modulators of α5-Containing GABABiological psychiatry · 2026Review
- A depression-like phenotype is associated with discrete defects in the primary hippocampal circuit.Translational psychiatry · 2026Article
- Digital Twin Brain simulation and manipulation of a functional brain network underlying mental illness.bioRxiv : the preprint server for biology · 2026Article
- Eukaryotic initiation factor 4E: a key factor of traumatic stress-induced depression-related cognitive decline at different age.Translational psychiatry · 2026Article
- GABADrug design, development and therapy · 2026Review
- Thalamic GABA+ levels are negatively associated with neuropsychiatric symptoms in patients with insomnia.Frontiers in human neuroscience · 2026Article
- Altered Bilateral Motor Cortex Excitability and Peripheral Glutamate/GABA Imbalance in Generalized Anxiety Disorder: A TMS Investigation.Psychology research and behavior management · 2026Article
- Concerted elevations of cortical and striatal glutamate and GABA in antipsychotic-free individuals at clinical high-risk for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Sex-specific GABAergic microcircuits that switch vulnerability into resilience to stress and reverse the effects of chronic stress exposure.Molecular psychiatry · 2025Article
- Transcriptome signatures of the medial prefrontal cortex underlying GABAergic control of resilience to chronic stress exposure.Molecular psychiatry · 2025Article
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Exogenous GABA Alleviates Tourette Syndrome-Like Behavior in Sprague-Dawley Rats by Altering Gut Microbiota and Striatum Metabolism.Neuropsychiatric disease and treatment · 2025Article
- The involvement of KTranslational psychiatry · 2024Review
- Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity.Environmental science and ecotechnology · 2024Article
- Activity in the dorsal hippocampus-mPFC circuit modulates stress-coping strategies during inescapable stress.Experimental & molecular medicine · 2024Article
- Effects of ketamine on GABAergic and glutamatergic activity in the mPFC: biphasic recruitment of GABA function in antidepressant-like responses.bioRxiv : the preprint server for biology · 2024Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMajor depressive disorder is increasingly recognized to involve functional deficits in both gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission. To elucidate the relationship between these phenotypes, we used GABAA receptor γ2 subunit heterozygous (γ2(+/-)) mice, which we previously characterized as a model animal with construct, face, and predictive validity for major depressive disorder.
methodsTo assess possible consequences of GABAergic deficits on glutamatergic transmission, we quantitated the cell surface expression of N-methyl-D-aspartate (NMDA)-type and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors and the function of synapses in the hippocampus and medial prefrontal cortex of γ2(+/-) mice. We also analyzed the effects of an acute dose of the experimental antidepressant ketamine on all these parameters in γ2(+/-) versus wild-type mice.
resultsModest defects in GABAergic synaptic transmission of γ2(+/-) mice resulted in a strikingly prominent homeostatic-like reduction in the cell surface expression of NMDA-type and AMPA-type glutamate receptors, along with prominent functional impairment of glutamatergic synapses in the hippocampus and medial prefrontal cortex. A single subanesthetic dose of ketamine normalized glutamate receptor expression and synaptic function of γ2(+/-) mice to wild-type levels for a prolonged period, along with antidepressant-like behavioral consequences selectively in γ2(+/-) mice. The GABAergic synapses of γ2(+/-) mice were potentiated by ketamine in parallel but only in the medial prefrontal cortex.
conclusionsDepressive-like brain states that are caused by GABAergic deficits involve a homeostatic-like reduction of glutamatergic transmission that is reversible by an acute, subanesthetic dose of ketamine, along with regionally selective potentiation of GABAergic synapses. The data merge the GABAergic and glutamatergic deficit hypotheses of major depressive disorder.
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