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Cell Rep. 2019 May 21;27(8):2249-2261.e7. doi: 10.1016/j.celrep.2019.04.078.

Transient, Consequential Increases in Extracellular Potassium Ions Accompany Channelrhodopsin2 Excitation.

Author information

1
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
2
IBM T.J. Watson Research Center, P.O. Box 218, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA.
3
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
4
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Intellectual and Developmental Disabilities Research Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA.
5
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: bkhakh@mednet.ucla.edu.

Abstract

Channelrhodopsin2 (ChR2) optogenetic excitation is widely used to study neurons, astrocytes, and circuits. Using complementary approaches in situ and in vivo, we found that ChR2 stimulation leads to significant transient elevation of extracellular potassium ions by ∼5 mM. Such elevations were detected in ChR2-expressing mice, following local in vivo expression of ChR2(H134R) with adeno-associated viruses (AAVs), in different brain areas and when ChR2 was expressed in neurons or astrocytes. In particular, ChR2-mediated excitation of striatal astrocytes was sufficient to increase medium spiny neuron (MSN) excitability and immediate early gene expression. The effects on MSN excitability were recapitulated in silico with a computational MSN model and detected in vivo as increased action potential firing in awake, behaving mice. We show that transient, physiologically consequential increases in extracellular potassium ions accompany ChR2 optogenetic excitation. This coincidental effect may be important to consider during astrocyte studies employing ChR2 to interrogate neural circuits and animal behavior.

KEYWORDS:

astrocyte; channelrhodopsin; circuit; neuron; optogenetics; potassium; striatum

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