Article abstract
Nature Methods 5, 895 - 902 (2008)
Published online: 14 September 2008 | doi:10.1038/nmeth.1252
Optogenetic analysis of synaptic function
Jana F Liewald1,5, Martin Brauner1,5, Greg J Stephens2, Magali Bouhours3, Christian Schultheis1, Mei Zhen3 & Alexander Gottschalk1,4
Abstract
We introduce optogenetic investigation of neurotransmission (OptIoN) for time-resolved and quantitative assessment of synaptic function via behavioral and electrophysiological analyses. We photo-triggered release of acetylcholine or 
-aminobutyric acid at Caenorhabditis elegans neuromuscular junctions using targeted expression of Chlamydomonas reinhardtii Channelrhodopsin-2. In intact Channelrhodopsin-2 transgenic worms, photostimulation instantly induced body elongation (for -aminobutyric acid) or contraction (for acetylcholine), which we analyzed acutely, or during sustained activation with automated image analysis, to assess synaptic efficacy. In dissected worms, photostimulation evoked neurotransmitter-specific postsynaptic currents that could be triggered repeatedly and at various frequencies. Light-evoked behaviors and postsynaptic currents were significantly (P 
0.05) altered in mutants with pre- or postsynaptic defects, although the behavioral phenotypes did not unambiguously report on synaptic function in all cases tested. OptIoN facilitates the analysis of neurotransmission with high temporal precision, in a neurotransmitter-selective manner, possibly allowing future investigation of synaptic plasticity in C. elegans.
- Institute of Biochemistry, Department of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt, Biocenter N220, Max von Laue Str. 9, D-60438 Frankfurt, Germany.
- Lewis Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Washington Road, Princeton University, Princeton, New Jersey 08544, USA.
- Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada.
- Cluster of Excellence Frankfurt—Macromolecular Complexes, Goethe University, Max von Laue Str. 3, D-60438 Frankfurt, Germany.
- These authors contributed equally to this work.
Correspondence to: Alexander Gottschalk1,4 e-mail: a.gottschalk@em.uni-frankfurt.de
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