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.
Wemmie
John A
JA
Department of Psychiatry, Howard Hughes Medical Institute, University of Iowa, Iowa City, IA 52242, USA.
Coryell
Matthew W
MW
Askwith
Candice C
CC
Lamani
Ejvis
E
Leonard
A Soren
AS
Sigmund
Curt D
CD
Welsh
Michael J
MJ
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