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.