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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.

Neurogastroenterology is defined as neurology of the gastrointestinal tract, liver, gallbladder and pancreas and encompasses control of digestion through the enteric nervous system (ENS), the central nervous system (CNS) and integrative centers in sympathetic ganglia. This Review provides a broad overview of the field of neurogastroenterology, with a focus on the roles of the ENS in the control of the musculature of the gastrointestinal tract and transmucosal fluid movement. Digestion is controlled through the integration of multiple signals from the ENS and CNS; neural signals also pass between distinct gut regions to coordinate digestive activity. Moreover, neural and endocrine control of digestion is closely coordinated. Interestingly, the extent to which the ENS or CNS controls digestion differs considerably along the digestive tract. The importance of the ENS is emphasized by the life-threatening effects of certain ENS neuropathies, including Hirschsprung disease and Chagas disease. Other ENS disorders, such as esophageal achalasia and gastroparesis, cause varying degrees of dysfunction. The neurons in enteric reflex pathways use a wide range of chemical messengers that signal through an even wider range of receptors. These receptors provide many actual and potential targets for modifying digestive function.

The stability of the neuronal circuits and cells of the enteric nervous system can no longer be taken for granted; new evidence suggests astounding rates of apoptosis and neurogenesis.

Little Brain Big Brain has been a biannual meeting organized and attended exclusively by young investigators in neurogastroenterology since 1989. The XIVth meeting featured cutting-edge work advancing several novel hypotheses in the main themes of motility, inflammation and metabolism.

Neurogastroenterology: Tasting the gut — enterochromaffin cells are chemosensitive and modulate sensory neurons

Neurogastroenterology: A shift in macrophage phenotype underlies age-related ENS degeneration

Neurogastroenterology encompasses intrinsic and extrinsic neural processes that regulate gut functions, sensation and related behaviors such as ingestion. In 2011, key advances were made in understanding gut–brain interactions, visceral sensation, serotonin signaling, neurogenesis and neuromuscular transmission.

Neurogastroenterology: A tale of two neurons — distinct functions of vagal afferents of the gut

Placebo analgesia is increasingly appreciated in many difficult to treat chronic functional gastrointestinal disorders such as IBS. However, investigations of interactions between psychological and biological placebo factors are still in early stages. Now, technologies have been developed that enable neural mechanisms of placebo analgesia to be studied more directly in humans.

Neurogastroenterology: ICC act as pacemakers to control segmentation motor activity in the gut

Neurogastroenterology: New approach enables live recordings of nerve activity in intestinal biopsy samples

Enteric glial cells enhance the repair of the intestinal epithelial barrier, partly by promoting epithelial restititution and intestinal epithelial cell spreading. “This study reinforces the concept that enteric glial cells are a central cellular component of the intestinal epithelial barrier microenvironment and that they have a major protective role towards the intestinal epithelial barrier,” says Michel Neunlist, corresponding author.

Neurogastroenterology: Modification of basal brain metabolism and neuronal activity is an acquired feature of obesity