Ataxia in the ASIC5 Knockout Mouse Associated with Decreased Excitability of Vestibulocerebellum Unipolar Brush Cells

Abstract

Acid‐sensing ion channels (ASICs) are neuronal ligand‐gated sodium channels. They are the members of the Degenerin/Epithelial Na+ channel (Deg/ENaC) family. In mammalian neurons ASICs play an important role in a variety of complex behaviors such as fear, pain, anxiety, learning, and memory. Among all five members of ASIC1‐5 channels, ASIC5 is least known. To reveal the expression and function of this channel we generated ASIC5 reporter and knockout mice. We found that ASIC5 is restrictively expressed in a subset of interneurons in the granular layer of nodulus of the vestibulocerebellum. Immunohistochemical and morphological analysis identified these interneurons as unipolar brush cells (UBC) that also express the metabotropic glutamate receptor 1α (mGluR1α). Such observations are consistent with ASIC5 playing a key role in the physiology of UBCs and in the function of the vestibulocerebellum. Consistent with this, knockout of ASIC5 results in ataxia and uncoordinated bodily movements. Electrophysiological analysis of UBC revealed a decrease in excitability of these neurons in the ASIC5 knockout mice that underlies these behavioral dysfunctions.Support or Funding InformationThis work was funded by a NIH Ro1 grant (DK113816)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.