Optogenetic analysis of synaptic function

被引：108

作者：

Liewald, Jana F. ^{[1
]}

Brauner, Martin ^{[1
]}

Stephens, Greg J. ^{[2
]}

Bouhours, Magali ^{[3
]}

Schultheis, Christian ^{[1
]}

Zhen, Mei ^{[3
]}

Gottschalk, Alexander ^{[1
,4
]}

机构：

[1] Goethe Univ Frankfurt, Inst Biochem, Dept Biochem Chem & Pharm, D-60438 Frankfurt, Germany

[2] Princeton Univ, Carl Icahn Lab, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA

[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[4] Goethe Univ Frankfurt, Cluster Excellence Frankfurt Macromol Complexes, D-60438 Frankfurt, Germany

来源：

NATURE METHODS | 2008年 / 5卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/NMETH.1252

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 gamma-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 gamma-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.

引用

页码：895 / 902

页数：8

共 31 条

[1] THE CAENORHABDITIS-ELEGANS UNC-17 GENE - A PUTATIVE VESICULAR ACETYLCHOLINE TRANSPORTER [J].

ALFONSO, A ;

GRUNDAHL, K ;

DUERR, JS ;

HAN, HP ;

RAND, JB .

SCIENCE, 1993, 261 (5121) :617-619

[2]

Bamber BA, 1999, J NEUROSCI, V19, P5348

[3] Millisecond-timescale, genetically targeted optical control of neural activity [J].

Boyden, ES ;

Zhang, F ;

Bamberg, E ;

Nagel, G ;

Deisseroth, K .

NATURE NEUROSCIENCE, 2005, 8 (09) :1263-1268

[4]

BRENNER S, 1974, GENETICS, V77, P71

[5] Bridging the gap between genes and behavior:: recent advances in the electrophysiological analysis of neural function in Caenorhabditis elegans [J].

Francis, MM ;

Mellem, JE ;

Maricq, AV .

TRENDS IN NEUROSCIENCES, 2003, 26 (02) :90-99

[6] Heterogeneity in synaptic transmission along a Drosophila larval motor axon [J].

Guerrero, G ;

Reiff, DF ;

Agarwal, G ;

Ball, RW ;

Borst, A ;

Goodman, CS ;

Isacoff, EY .

NATURE NEUROSCIENCE, 2005, 8 (09) :1188-1196

[7] Open syntaxin docks synaptic vesicles [J].

Hammarlund, Marc ;

Palfreyman, Mark T. ;

Watanabe, Shigeki ;

Olsen, Shawn ;

Jorgensen, Erik M. .

PLOS BIOLOGY, 2007, 5 (08) :1695-1711

[8] Mutations in synaptojanin disrupt synaptic vesicle recycling [J].

Harris, TW ;

Hartwieg, E ;

Horvitz, HR ;

Jorgensen, EM .

JOURNAL OF CELL BIOLOGY, 2000, 150 (03) :589-599

[9] DEFECTIVE RECYCLING OF SYNAPTIC VESICLES IN SYNAPTOTAGMIN MUTANTS OF CAENORHABDITIS-ELEGANS [J].

JORGENSEN, EM ;

HARTWIEG, E ;

SCHUSKE, K ;

NONET, ML ;

JIN, YS ;

HORVITZ, HR .

NATURE, 1995, 378 (6553) :196-199

[10] Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopin and green algae channelrhodopsin [J].

Li, X ;

Gutierrez, DV ;

Hanson, MG ;

Han, J ;

Mark, MD ;

Chiel, H ;

Hegemann, P ;

Landmesser, LT ;

Herlitze, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (49) :17816-17821

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