Ventral Hippocampus Circuits Underlying Conditioned Feeding Behavior

7.项目总结/摘要 在过去的30年里，肥胖症的流行已经发展到超过三分之二的成年人被归类为 超重或肥胖，约六分之一的儿童和青少年被认为患有肥胖症1，7。的 肥胖症流行率的惊人增长在很大程度上是由于膳食的大小和数量的增加 人们的消费量33，34，这通常会受到经验和环境食物的影响- 相关的线索，可以驱动一个人吃超过代谢/能量需要10，11。近期出版物 我们的实验室4，5表明腹侧海马（CA 1v）投射到外侧下丘脑的重要作用 在调节进食的条件和动机方面， 行为然而，CA 1v神经通路和行为机制的整合食物相关的 内部和环境线索没有被充分表征。本提案的目标是[1]绘制主要 CA 1v神经元的一阶投射，[2]识别从CA 1v>mPFC分支的侧支通路， CA 1v>LHA途径，[3]确定CA 1v>mPFC和CA 1v>LHA的二阶投影输出 路径（目标I）。该提案还旨在测试CA 1v>mPFC和CA 1v>LHA的功能相关性 通过结合病毒介导的CA 1v通路断开与 啮齿动物喂养相关的行为模式，探测记忆过程相关的内部和外部 喂食相关线索（Aim II）。总体而言，拟议的实验评估了多个水平的分析和利用 最先进的方法，包括条件病毒发生神经通路追踪和功能 化学遗传学的方法来解开神经回路连接学习和记忆与喂养行为。

7. PROJECT SUMMARY/ABSTRACT Over the past 30 years, the obesity epidemic has grown such that more than 2 in 3 adults are classified as overweight or obese, and about 1 in 6 children and adolescents are considered to have obesity 1,7. The alarming increase in the prevalence of obesity is in large part due to the increasing size and number of meals that people consume 33,34, which are often influenced by learned experiences and environmental food- associated cues that can drive an individual to eat beyond metabolic/energy need 10,11. Recent publications from our lab4,5 indicate an important role for ventral hippocampus (CA1v) projections to the lateral hypothalamic area (LHA) and medial prefrontal cortex (mPFC) in mediating conditioned and motivated aspects of feeding behavior. However, CA1v neural pathways and behavioral mechanisms for the integration of food-related internal and environmental cues are not fully characterized. The goals of this proposal are to [1] map primary 1st-order projections of CA1v neurons, [2] identify collateral pathways branching from CA1v>mPFC and CA1v>LHA pathways, and [3] determine 2nd-order projection outputs of CA1v>mPFC and CA1v>LHA pathways (Aim I). This proposal also aims to test the functional relevance of CA1v>mPFC and CA1v>LHA pathways to higher-order aspects of feeding by combining viral-mediated disconnection of CA1v pathways with rodent feeding-relevant behavior paradigms that probe memory processes related to internal and external feeding-relevant cues (Aim II). Overall proposed experiments assess multiple levels of analyses and utilize state-of-the-art methodologies, including conditional virogenetic neural pathway tracing and functional chemogenetic methods to unravel the neural circuits that connect learning and memory with feeding behavior.