Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues

Nat Neurosci. 1999 Sep;2(9):833-9. doi: 10.1038/12207.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / physiopathology*
  • Anxiety / psychology
  • Anxiety Disorders / genetics
  • Anxiety Disorders / physiopathology
  • Anxiety Disorders / psychology
  • Avoidance Learning / physiology
  • Conditioning, Operant
  • Cues*
  • Fear
  • Heterozygote
  • Hippocampus / physiology*
  • Hippocampus / physiopathology
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Neurons / drug effects
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Receptors, GABA-A / genetics
  • Receptors, GABA-A / physiology*
  • gamma-Aminobutyric Acid / pharmacology


  • Receptors, GABA-A
  • gamma-Aminobutyric Acid