Animals have the remarkable ability to respond to a wide variety of internal need states with appropriate behaviors in order to restore homeostasis. One of these need states is dehydration, which generates thirst and leads to drinking in order to restore proper water balance. Recently, we and others have shown that activity of subfornical organ (SFO) excitatory and inhibitory neurons drive and inhibit drinking behavior in mice, respectively, providing an entry point for analysis of this neural circuit. We will study the circut downstream of SFO excitatory and inhibitory populations in mice by systematically testing the behavioral function of their axonal projections to key brain areas. In addition, we will identify te key signals that regulate the activity SFO excitatory and inhibitory neurons in vivo during water deprivation and rehydration. This work will further our fundamental understanding of the generation of thirst in the brain. Importantly, this work will also contribute to our understandingof other motivated behaviors, such as feeding and drug-seeking. Finally, the same neural circuits that induce thirst influence other aspects of body fluid regulation, such as blood pressure and cardiovascular output, making these circuits potential therapeutic targets with relevance for hypertension, cardiovascular disease, and stroke.

Public Health Relevance

This project will investigate the behavioral functions and regulation of two neural populations in the subfornical organ of the brain implicated in the generation of thirst. This work will shed light on the generation of motivated behaviors, including food consumption and drug seeking. The neural circuits associated with these populations may also represent therapeutic targets with relevance for hypertension, cardiovascular disease, stroke, and anxiety disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HL131463-02
Application #
9238466
Study Section
Special Emphasis Panel (ZRG1-F01B-G (20)L)
Program Officer
Meadows, Tawanna
Project Start
2016-02-02
Project End
2019-02-01
Budget Start
2017-02-02
Budget End
2018-02-01
Support Year
2
Fiscal Year
2017
Total Cost
$35,043
Indirect Cost
Name
University of California San Francisco
Department
Physiology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Zimmerman, Christopher A; Lin, Yen-Chu; Leib, David E et al. (2016) Thirst neurons anticipate the homeostatic consequences of eating and drinking. Nature 537:680-684