Overexpression of acid-sensing ion channel 1a in transgenic mice increases acquired fear-related behavior.
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.
Department of Psychiatry, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
John A
JA
Wemmie
Matthew W
MW
Coryell
Candice C
CC
Askwith
Ejvis
E
Lamani
A Soren
AS
Leonard
Curt D
CD
Sigmund
Michael J
MJ
Welsh
D062565:Acid Sensing Ion Channels; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D003213:Conditioning, Psychological; D004274:DNA, Recombinant / Q000235:genetics; D005239:Fear / Q000502:physiology*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015222:Sodium Channels / Q000235:genetics* / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism
C568266:ASIC1 protein, human; C568267:ASIC1 protein, mouse; D062565:Acid Sensing Ion Channels; D004274:DNA, Recombinant; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D015222:Sodium Channels