ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cell-type specific deletion of GABA(A)α1 in corticotropin-releasing factor-containing neurons enhances anxiety and disrupts fear extinction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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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.
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Who cites it
66 citing papers in PubMed, 97 citations in OpenAlex.
- GABACellular and molecular neurobiology · 2026Review
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- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Emphasizing the Crosstalk Between Inflammatory and Neural Signaling in Post-traumatic Stress Disorder (PTSD).Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Resveratrol Attenuates Chronic Unpredictable Mild Stress-Induced Alterations in the SIRT1/PGC1α/SIRT3 Pathway and Associated Mitochondrial Dysfunction in Mice.Molecular neurobiology · 2023Article
- GABA tone regulation and its cognitive functions in the brain.Nature reviews. Neuroscience · 2023Review
- Distinct populations of corticotropin-releasing factor (CRF) neurons mediate divergent yet complementary defensive behaviors in response to a threat.Neuropharmacology · 2023Review
- Hyperexcitability: From Normal Fear to Pathological Anxiety and Trauma.Frontiers in systems neuroscience · 2022Review
- Corticotropin releasing factor and norepinephrine related circuitry changes in the bed nucleus of the stria terminalis in stress and alcohol and substance use disorders.Neuropharmacology · 2021Review
- Presynaptic GABAPsychopharmacology · 2021Article
- Reciprocal control of obesity and anxiety-depressive disorder via a GABA and serotonin neural circuit.Molecular psychiatry · 2021Article
- GABA synaptopathy promotes the elevation of caspases 3 and 9 as pro-apoptotic markers in Egyptian patients with autism spectrum disorder.Acta neurologica Belgica · 2021Article
- Genome-wide translational profiling of amygdala Crh-expressing neurons reveals role for CREB in fear extinction learning.Nature communications · 2020Article
- Effects of chronic silencing of relaxin-3 production in nucleus incertus neurons on food intake, body weight, anxiety-like behaviour and limbic brain activity in female rats.Psychopharmacology · 2020Article
- Translating Across Circuits and Genetics Toward Progress in Fear- and Anxiety-Related Disorders.The American journal of psychiatry · 2020Review
- GABAergic System in Stress: Implications of GABAergic Neuron Subpopulations and the Gut-Vagus-Brain Pathway.Neural plasticity · 2020Review
- Looking for Novelty in an "Old" Receptor: Recent Advances Toward Our Understanding of GABAFrontiers in neuroscience · 2020Review
- Sex differences in fear extinction.Neuroscience and biobehavioral reviews · 2019Review
- Sex-Dependent Modulation of Anxiety and Fear by 5-HTACS chemical neuroscience · 2019Article
- Chronic stress induces cell type-selective transcriptomic and electrophysiological changes in the bed nucleus of the stria terminalis.Neuropharmacology · 2019Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Corticotropin-releasing factor (CRF) is critical for the endocrine, autonomic, and behavioral responses to stressors, and it has been shown to modulate fear and anxiety. The CRF receptor is widely expressed across a variety of cell types, impeding progress toward understanding the contribution of specific CRF-containing neurons to fear dysregulation. We used a unique CRF-Cre driver transgenic mouse line to remove floxed GABA(A)α1 subunits specifically from CRF neurons [CRF-GABA(A)α1 KO]. This process resulted in mice with decreased GABA(A)α1 expression only in CRF neurons and increased CRF mRNA within the amygdala, bed nucleus of the stria terminalis (BNST) and paraventricular nucleus of the hypothalamus. These mice show normal locomotor and pain responses and no difference in depressive-like behavior or Pavlovian fear conditioning. However, CRF-GABA(A)α1 KO increased anxiety-like behavior and impaired extinction of conditioned fear, coincident with an increase in plasma corticosterone concentration. These behavioral impairments were rescued with systemic or BNST infusion of the CRF antagonist R121919. Infusion of Zolpidem, a GABA(A)α1-preferring benzodiazepine-site agonist, into the BNST of the CRF-GABA(A)α1 KO was ineffective at decreasing anxiety. Electrophysiological findings suggest a disruption in inhibitory current may play a role in these changes. These data indicate that disturbance of CRF containing GABA(A)α1 neurons causes increased anxiety and impaired fear extinction, both of which are symptoms diagnostic for anxiety disorders, such as posttraumatic stress disorder.
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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.