Interoceptive receptive fields and functional architecture of physiological control in the mouse brainstem

Abstract

Our external senses of sight, smell, sound, touch, and taste enable us to perceive the external world. In addition, our viscerosensory system monitors the physiological state of peripheral organs. This bodily sensory system orchestrates multi-organ physiological responses, regulating feeding, drinking, sickness behaviors, and generating the internal senses such as satiety, hunger, nausea, visceral malaise. In comparison to external sensory systems, the principles that define visceral sensory processing remain poorly defined. We developed a two-photon calcium imaging preparation to understand internal organ representations in the nucleus of the solitary tract (NTS), a sensory gateway in the brainstem that receives bodily signals mostly via the vagus nerve. Combining the imaging platform with stimulation of multiple visceral organs, we uncover diverse neuronal responses to internal stimuli, while functionally defined cell-types are highly organized within the NTS. Combining functional imaging with pharmacogenetic manipulations and viral tracing from genetically defined vagal sensory cell types, we show that the highly organized representations of internal senses are generated by vagal axon sorting and higher-order sensory processing within the NTS. Using a newly developed spatially patterned optogenetic stimulation system, we showed that stimulating different spatial domains of the NTS differentially modulates autonomic functions. Together, our study reveals basic coding principles used by the brain to process visceral inputs and sheds light on the treatment of viscerosensory and autonomic diseases, including obesity, diabetes, eating disorders, and neuroimmune diseases. The work was supported by NIH grants to S.D.L. (DP1 AT009497, R01 DK122976 and R01 DK103703), the Food Allergy Science Initiative, and a Leonard and Isabelle Goldenson Postdoctoral Fellowship, a Harvard Brain Science Initiative Young Investigator Transitions Award, and an American Diabetes Association Postdoctoral Fellowship to C.R. S.D.L. is an investigator of the Howard Hughes Medical Institute. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.