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Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior

Authors
  • John A. Wemmie
  • Matthew W. Coryell
  • Candice C. Askwith
  • Ejvis Lamani
  • A. Soren Leonard
  • Curt D. Sigmund
  • Michael J. Welsh
Publisher
National Academy of Sciences
Publication Date
Feb 26, 2004
Source
PMC
Keywords
License
Unknown

Abstract

The acid-sensing ion channel 1a (ASIC1a) is abundantly expressed in the amygdala complex and other brain regions associated with fear. Studies of mice with a disrupted ASIC1 gene suggested that ASIC1a may contribute to learned fear. To test this hypothesis, we generated mice overexpressing human ASIC1a by using the pan-neuronal synapsin 1 promoter. Transgenic ASIC1a interacted with endogenous mouse ASIC1a and was distributed to the synaptosomal fraction of brain. Transgenic expression of ASIC1a also doubled neuronal acid-evoked cation currents. The amygdala showed prominent expression, and overexpressing ASIC1a enhanced fear conditioning, an animal model of acquired anxiety. These data raise the possibility that ASIC1a and H+-gated currents may contribute to the development of abnormal fear and to anxiety disorders in humans.

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