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.
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.
|Leib, David E; Zimmerman, Christopher A; Poormoghaddam, Ailar et al. (2017) The Forebrain Thirst Circuit Drives Drinking through Negative Reinforcement. Neuron 96:1272-1281.e4|
|Zimmerman, Christopher A; Leib, David E; Knight, Zachary A (2017) Neural circuits underlying thirst and fluid homeostasis. Nat Rev Neurosci 18:459-469|
|Leib, David E; Zimmerman, Christopher A; Knight, Zachary A (2016) Thirst. Curr Biol 26:R1260-R1265|
|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|