PACα– an optogenetic tool for in vivo manipulation of cellular cAMP levels, neurotransmitter release, and behavior in Caenorhabditis elegans

Authors

  • Simone Weissenberger,

    1. Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Frankfurt, Germany
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    • The present address of Simone Weissenberger is the Institute for Toxicology, University Wuerzburg, Versbacher Str. 9, D-97078 Wuerzburg, Germany.

    • These authors contributed equally to this study.

  • Christian Schultheis,

    1. Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Frankfurt, Germany
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    • These authors contributed equally to this study.

  • Jana Fiona Liewald,

    1. Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Frankfurt, Germany
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    • These authors contributed equally to this study.

  • Karen Erbguth,

    1. Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Frankfurt, Germany
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  • Georg Nagel,

    1. University Wuerzburg, Botanik I, Wuerzburg, Germany
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  • Alexander Gottschalk

    1. Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Frankfurt, Germany
    2. Frankfurt Institute for Molecular Life Sciences (FMLS), Goethe-University, Frankfurt, Germany
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Address correspondence and reprint requests to Alexander Gottschalk, Department of Biochemistry, Chemistry, and Pharmacy, Institute of Biochemistry, Goethe-University, Max-von-Laue-Straße 9, D-60438 Frankfurt, Germany. E-mail: a.gottschalk@em.uni-frankfurt.de

Abstract

J. Neurochem. (2011) 116, 616–625.

Abstract

Photoactivated adenylyl cyclase α (PACα) was originally isolated from the flagellate Euglena gracilis. Following stimulation by blue light it causes a rapid increase in cAMP levels. In the present study, we expressed PACα in cholinergic neurons of Caenorhabditis elegans. Photoactivation led to a rise in swimming frequency, speed of locomotion, and a decrease in the number of backward locomotion episodes. The extent of the light-induced behavioral effects was dependent on the amount of PACα that was expressed. Furthermore, electrophysiological recordings from body wall muscle cells revealed an increase in miniature post-synaptic currents during light stimulation. We conclude that the observed effects were caused by cAMP synthesis because of photoactivation of pre-synaptic PACα which subsequently triggered acetylcholine release at the neuromuscular junction. Our results demonstrate that PACα can be used as an optogenetic tool in C. elegans for straightforward in vivo manipulation of intracellular cAMP levels by light, with good temporal control and high cell specificity. Thus, using PACα allows manipulation of neurotransmitter release and behavior by directly affecting intracellular signaling.

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