A Method for Activation of Endogenous Acid Sensing Ion Channel-1a (ASIC1a) in the Nervous System with High Spatial and Temporal Precision [Membrane Biology]

April 11th, 2014 by Li, T., Yang, Y., Canessa, C. M.

Protons activate ASIC1a in the central nervous system (CNS), though the impact of such activation on brain outputs remains elusive. Progress elucidating the functional roles of ASIC1a in the CNS has been hinder by technical difficulties of achieving acidification with spatial and temporal precision. We have implemented a method to control optically the opening of ASIC1a in brain slices and also in awake animals. The light-driven H+ pump ArchT was expressed in astrocytes of mouse cortex by injection of adenoviral vectors containing a strong and astrocyte-specific promoter. Illumination with amber light acidified the surrounding interstitium and led to activation of endogenous ASIC1a channels and firing of action potentials in neurons localized in close proximity to ArchT-expressing astrocytes. We conclude that this optogenetic method offers a minimally invasive approach that enables examining the biological consequences of ASIC1a currents in any structure of the CNS and in the modulation of animal behaviors.
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