Transient, Consequential Increases in Extracellular Potassium Ions Accompany Channelrhodopsin2 Excitation
J. Christopher Octeau,
Mohitkumar R. Gangwani,
Sushmita L. Allam,
Duy Tran,
Shuhan Huang,
Tuan M. Hoang-Trong,
Peyman Golshani,
Timothy H. Rumbell,
James R. Kozloski,
Baljit S. Khakh
Affiliations
J. Christopher Octeau
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA
Mohitkumar R. Gangwani
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA
Sushmita L. Allam
IBM T.J. Watson Research Center, P.O. Box 218, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA
Duy Tran
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA
Shuhan Huang
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095-1751, USA
Tuan M. Hoang-Trong
IBM T.J. Watson Research Center, P.O. Box 218, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA
Peyman Golshani
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
Timothy H. Rumbell
IBM T.J. Watson Research Center, P.O. Box 218, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA
James R. Kozloski
IBM T.J. Watson Research Center, P.O. Box 218, 1101 Kitchawan Road, Yorktown Heights, NY 10598, USA
Baljit S. Khakh
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; Corresponding author
Summary: 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. : Using multiple approaches, Octeau et al. discover that optogenetic excitation of ChR2-expressing cells leads to significant transient extracellular potassium ion elevations that increase neuronal excitability and immediate early gene expression in neurons following in vivo stimulation. Keywords: potassium, astrocyte, striatum, neuron, circuit, optogenetics, channelrhodopsin
