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  • Review Article
  • Published:

Optogenetic and chemogenetic techniques for neurogastroenterology

Nature Reviews Gastroenterology & Hepatology volume 15, pages 21–38 (2018)Cite this article

Subjects

Key Points

  • Optogenetic actuators are light-driven proteins able to perturb electrochemical signals, whereas optogenetic indicators are capable of reporting changes in cellular activity

  • Chemogenetic actuators are engineered receptors that are activated or inhibited by synthetic ligands to alter cellular signal transduction

  • Optogenetic and chemogenetic tools involve genetically encoded proteins that can be targeted to specific cell types via a variety of transgene expression strategies

  • The methods to deliver light and designer drugs need to be carefully selected and depend on whether experiments are to be conducted on organs, multiple cells or single cells

  • In combination with advances in microscopy, optogenetics and chemogenetics provide tools that can be used to investigate the role of specific cell types and signalling pathways in gastrointestinal function

Abstract

Optogenetics and chemogenetics comprise a wide variety of applications in which genetically encoded actuators and indicators are used to modulate and monitor activity with high cellular specificity. Over the past 10 years, development of these genetically encoded tools has contributed tremendously to our understanding of integrated physiology. In concert with the continued refinement of probes, strategies to target transgene expression to specific cell types have also made much progress in the past 20 years. In addition, the successful implementation of optogenetic and chemogenetic techniques thrives thanks to ongoing advances in live imaging microscopy and optical technology. Although innovation of optogenetic and chemogenetic methods has been primarily driven by researchers studying the central nervous system, these techniques also hold great promise to boost research in neurogastroenterology. In this Review, we describe the different classes of tools that are currently available and give an overview of the strategies to target them to specific cell types in the gut wall. We discuss the possibilities and limitations of optogenetic and chemogenetic technology in the gut and provide an overview of their current use, with a focus on the enteric nervous system. Furthermore, we suggest some experiments that can advance our understanding of how the intrinsic and extrinsic neural networks of the gut control gastrointestinal function.

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Figure 1
Figure 2: Schematic overview of available genetically encoded actuators and indicators.
Figure 3: Schematic overview of strategies to target genetically encoded tools to specific cell types.
Figure 4: Different methods to express GCaMPs in the enteric nervous system.
Figure 5: Stimulation and excitation methods for optogenetic and chemogenetic experiments in neurogastroenterology.
Figure 6: Different methods of expressing channelrhodopsin 2 in the enteric nervous system.

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Acknowledgements

The authors' work is supported by the Research Foundation Flanders (FWO) grant G.0921.15 and Methusalem /14/05, University of Leuven, Belgium. M.M.H. and W.B. were supported by postdoctoral fellowships from FWO. M.M.H. is a National Health and Medical Research Council fellow. The authors thank G. Matteoli for the use of R26R–ChR2 mice.

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  1. Laboratory for Enteric Neuroscience (LENS), Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, O&N 1 Box 701, Leuven, 3000, Belgium

    Werend Boesmans, Marlene M. Hao & Pieter Vanden Berghe

  2. Department of Pathology, Maastricht University Medical Center, P. Debeijelaan 25, Maastricht, 6229 HX, The Netherlands

    Werend Boesmans

  3. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, 3010, Victoria, Australia

    Marlene M. Hao

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Correspondence to Pieter Vanden Berghe.

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Boesmans, W., Hao, M. & Vanden Berghe, P. Optogenetic and chemogenetic techniques for neurogastroenterology. Nat Rev Gastroenterol Hepatol 15, 21–38 (2018). https://doi.org/10.1038/nrgastro.2017.151

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