ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in the lateral amygdala and conditioned fear generalization.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- ICER-Controlled inhibitory plasticity of amygdala engram neurons regulates fear memory precision.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Neural mechanisms of fear memory precision and generalization: from auditory cortex to amygdala.Translational psychiatry · 2026Review
- Genetic-Epigenetic Interplay in Epilepsy: Pathways, Biomarkers, and Epigenome-Targeted Therapies.Epigenomes · 2026Review
- Presynaptic Trafficking of Glutamate Decarboxylase Isoforms Is Dispensable for Basal GABAergic Neurotransmission.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- A transcriptomic resource for glial GABA-associated ASH neuronal aging and candidate pathways.Frontiers in aging neuroscience · 2026Article
- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- A Proton Magnetic Resonance Spectroscopy (International journal of molecular sciences · 2025Article
- A comprehensive review of GABA in autism spectrum disorders: associations, mechanisms, and therapeutic implications.Frontiers in psychiatry · 2025Review
- Microbiome Metabolomic Analysis of the Anxiolytic Effect of Baihe Dihuang Decoction in a Rat Model of Chronic Restraint Stress.Drug design, development and therapy · 2024Article
- A combinatory genetic strategy for targeting neurogliaform neurons in the mouse basolateral amygdala.Frontiers in cellular neuroscience · 2024Article
- Insights into the leveraging of GABAergic signaling in cancer therapy.Cancer medicine · 2023Review
- Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats.Genes · 2023Article
- The role of BDNF in mediating the prophylactic effects of (R,S)-ketamine on fear generalization and extinction.Translational psychiatry · 2022Article
- Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal.Molecules (Basel, Switzerland) · 2022Article
- Impact of T cells on neurodegeneration in anti-GAD65 limbic encephalitis.Annals of clinical and translational neurology · 2021Article
- Sex differences in fear memory consolidation via Tac2 signaling in mice.Nature communications · 2021Article
- Genetic deletion of the 67-kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats.FEBS open bio · 2021Article
- Insights: fear of GAD.FEBS open bio · 2021Article
- Brain-Derived Neurotrophic Factor/Tropomyosin Receptor Kinase B Signaling Controls Excitability and Long-Term Depression in Oval Nucleus of the BNST.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Disruption of the GABAergic system contributes to the development of perioperative neurocognitive disorders after anesthesia and surgery in aged mice.CNS neuroscience & therapeutics · 2020Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major neurobiological pathomechanism of anxiety, and the amygdala is a key brain region involved. Reduced GABA levels have been found in anxiety patients, and genetic variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, have been associated with anxiety phenotypes in both humans and mice. These findings prompted us to hypothesize that a deficiency of GAD65, the GAD isoform controlling the availability of GABA as a transmitter, affects synaptic transmission and plasticity in the lateral amygdala (LA), and thereby interferes with fear responsiveness. Results indicate that genetically determined GAD65 deficiency in mice is associated with (1) increased synaptic length and release at GABAergic connections, (2) impaired efficacy of GABAergic synaptic transmission and plasticity, and (3) reduced spillover of GABA to presynaptic GABAB receptors, resulting in a loss of the associative nature of long-term synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition, training with high shock intensities in wild-type mice mimicked the phenotype of GAD65 deficiency at both the behavioral and synaptic level, indicated by generalization of conditioned fear and a loss of the associative nature of synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient GABAergic synaptic transmission and plasticity, and for maintaining extracellular GABA at a level needed for associative plasticity at cortical inputs in the LA, which, if disturbed, results in an impairment of the cue specificity of conditioned fear responses typifying anxiety disorders.
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