Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors

Steven J. Husson, Wagner Steuer Costa, Sebastian Wabnig, Jeffrey N. Stirman, Joseph D. Watson, W. Clay Spencer, Jasper Akerboom, Loren L. Looger, Millet Treinin, David M. Miller, Hang Lu, Alexander Gottschalk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Background: Nociception generally evokes rapid withdrawal behavior in order to protect the tissue from harmful insults. Most nociceptive neurons responding to mechanical insults display highly branched dendrites, an anatomy shared by Caenorhabditis elegans FLP and PVD neurons, which mediate harsh touch responses. Although several primary molecular nociceptive sensors have been characterized, less is known about modulation and amplification of noxious signals within nociceptor neurons. First, we analyzed the FLP/PVD network by optogenetics and studied integration of signals from these cells in downstream interneurons. Second, we investigated which genes modulate PVD function, based on prior single-neuron mRNA profiling of PVD. Results: Selectively photoactivating PVD, FLP, and downstream interneurons via Channelrhodopsin-2 (ChR2) enabled the functional dissection of this nociceptive network, without interfering signals by other mechanoreceptors. Forward or reverse escape behaviors were determined by PVD and FLP, via integration by command interneurons. To identify mediators of PVD function, acting downstream of primary nocisensor molecules, we knocked down PVD-specific transcripts by RNAi and quantified light-evoked PVD-dependent behavior. Cell-specific disruption of synaptobrevin or voltage-gated Ca 2+ channels (VGCCs) showed that PVD signals chemically to command interneurons. Knocking down the DEG/ENaC channel ASIC-1 and the TRPM channel GTL-1 indicated that ASIC-1 may extend PVD's dynamic range and that GTL-1 may amplify its signals. These channels act cell autonomously in PVD, downstream of primary mechanosensory molecules. Conclusions: Our work implicates TRPM channels in modifying excitability of and DEG/ENaCs in potentiating signal output from a mechano-nociceptor neuron. ASIC-1 and GTL-1 homologs, if functionally conserved, may denote valid targets for novel analgesics.

Original languageAmerican English
Pages (from-to)743-752
Number of pages10
JournalCurrent Biology
Issue number9
StatePublished - 8 May 2012

Bibliographical note

Funding Information:
We thank the Caenorhabditis Genetics Centre (CGC; supported by the NIH, National Center for Research Resources) for providing strains. We are grateful to K. Preckel and B. Rummel for expert technical assistance, to H. Hutter, C. Bargmann, and W. Schafer for sharing reagents, to M. Goodman for communicating results prior to publication, and to M. Goodman, W. Schafer, and M. Zhen for comments on the manuscript. S.J.H. was supported by the Human Frontiers Science Program Organization (HFSPO) and the Research Fund Flanders (FWO-Vlaanderen). This work was supported by grants from the US-Israel Binational Science Foundation Grant 2005036 (M.T. and D.M.M.), NIH R01 NS26115 and R21 NS06882 (D.M.M.), NIH T32 MH64913 and F31 NS49743 (J.D.W.), NIH P30 CA68485, P60 DK20593, P30 DK58404, HD15052, P30 EY08126, and PO1 HL6744 to Vanderbilt University, as well as by grants from the DFG (SFB807, FOR1279, Cluster of Excellence Frankfurt [CEF-MC]; EXC115/1) and the Schram foundation to A.G.


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