Sequencing Neural Circuits Controlling Thermoregulation

University Of California, San Francisco, San Francisco CA

Investigators

Linked publications, trials & patents

Abstract

? DESCRIPTION (provided by applicant): One the most remarkable features of animals is their ability to sense changes in their internal physiologic state and then generate flexible behaviors that restore homeostasis. These survival processes are mediated by neural circuits in the brain that sense the state of the body and then convert this information into specific behavioral and autonomic responses. However our understanding of these homeostatic circuits has remained limited due to their structural complexity, as they are embedded within brain regions that contain a vast diversity of intermingled neural cell types. Understanding how this vast cellular diversity s organized into circuits that give rise to behavior is one of the central challenges in neuroscience I describe in this proposal how we have used a technology for activity-dependent RNA sequencing to generate a map of the key thermoregulatory neurons in the mouse brain. I then describe how we will develop two new technologies that will allow us to delineate the complete neural circuit that is downstream of these thermosensitive cells. These transformative new technologies enable the molecular identification of neurons that are anatomically or functionally connected and thereby allow for the first time the systematic application of RNA sequencing to deconstruct the cellular organization of neural circuits in the brain. I further outline how we wil use these new approaches to investigate the logic underlying the distributed and overlapping structure of neural circuits that mediate various aspects of physiologic homeostasis. This analysis takes advantage of information about the cellular organization of these circuits that could not be generated without the new technologies described in this proposal. Thus the experiments in this proposal will generate new tools for the neuroscience community and further apply these tools to address fundamental questions about the neural mechanisms that control homeostatic processes such as thermoregulation and feeding.