Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues
Abstract
Patients with panic disorders show a deficit of GABAA receptors in the hippocampus, parahippocampus and orbitofrontal cortex. Synaptic clustering of GABAA receptors in mice heterozygous for the gamma2 subunit was reduced, mainly in hippocampus and cerebral cortex. The gamma2 +/- mice showed enhanced behavioral inhibition toward natural aversive stimuli and heightened responsiveness in trace fear conditioning and ambiguous cue discrimination learning. Implicit and spatial memory as well as long-term potentiation in hippocampus were unchanged. Thus gamma2 +/- mice represent a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations. This model implicates GABAA-receptor dysfunction in patients as a causal predisposition to anxiety disorders.
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Global heterozygous knockdown of the γ2 subunit leads to impaired GABAergic signaling.
“Global heterozygous knockdown of the γ2 subunit leads to impaired GABAergic signaling [11 ], as well as anxiety- and despair-like behavior that is reversed with chronic desipramine (but not fluoxetine) [127] and acute ketamine [126] treatment.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [11]
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- Authors
- Crestani, F., Lorez, M., Baer, K., Essrich, C., Benke, D., Laurent, J. P., Belzung, C., Fritschy, J.-M., Lüscher, B., & Mohler, H.
- Affiliations
- University of Zurich (CH)
- Université de Tours (FR)
- Pennsylvania State University (US)
- Venue
- Nature Neuroscience
- Published
- 1999-09
- Volume
- 2
- Issue
- 9
- Pages
- 833-839
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W1602497443
- Cited by
- 550
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 40 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 7 · 2019: 21 · 2018: 13 · 2017: 19 · 2016: 15 · 2015: 15 · 2014: 29 · 2013: 8 · 2012: 25
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- gamma2 subunit, anxiety, panic disorder, harm avoidance, trace fear conditioning, hippocampus, negative association
- MeSH terms
- Animals, Anxiety, Anxiety Disorders, Avoidance Learning, Conditioning, Operant, Cues, Fear, gamma-Aminobutyric Acid, Heterozygote, Hippocampus, Memory, Mice, Inbred C57BL, Mice, Inbred Strains, Neurons, Receptors, GABA-A, Patch-Clamp Techniques, Maze Learning, Mice
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