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

 描述（由申请人提供）：动物具有通过适当行为对各种内部需求状态做出反应的显著能力，以恢复稳态。这些需求状态之一是脱水，这会产生口渴，并导致饮水，以恢复适当的水平衡。最近，我们和其他人已经表明，穹窿下器官（SFO）兴奋性和抑制性神经元的活动，分别驱动和抑制小鼠的饮酒行为，提供了一个切入点，分析这种神经回路。我们将通过系统地测试SFO兴奋性和抑制性群体向关键脑区的轴突投射的行为功能来研究小鼠SFO下游的回路。此外，我们将确定在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口渴产生的基本理解。重要的是，这项工作也将有助于我们理解其他动机行为，如喂养和药物寻求。最后，引起口渴的相同神经回路影响体液调节的其他方面，例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.