Cell-type-specific investigation of the neural circuits that control thirst

 描述(由申请者提供)：动物具有非凡的能力，能够以适当的行为对各种内部需求状态做出反应，以恢复体内平衡。其中一种需要状态是脱水，它会产生口渴并导致饮酒，以恢复适当的水平衡。最近，我们和其他人发现穹隆下器(SFO)兴奋性神经元和抑制性神经元的活动分别驱动和抑制小鼠的饮酒行为，为分析这一神经回路提供了一个切入点。我们将通过系统地测试它们向关键脑区的轴突投射的行为功能，来研究小鼠SFO兴奋和抑制群体下游的环路。此外，我们还将确定在体内缺水和复水过程中调节SFO兴奋性和抑制性神经元活性的关键信号。这项工作将进一步加深我们对大脑中产生口渴的基本理解。重要的是，这项工作还将有助于我们理解其他动机行为，如进食和寻求毒品。最后，引起口渴的神经回路影响体液调节的其他方面，如血压和心血管输出，使这些回路成为与高血压、心血管疾病和中风相关的潜在治疗靶点。

 DESCRIPTION (provided by applicant): 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.