Ventral Hippocampus Circuits Underlying Conditioned Feeding Behavior

7.项目摘要/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 超重或肥胖，每6个儿童和青少年中就有1个被认为患有肥胖症1，7。 肥胖率的惊人增长在很大程度上是由于用餐的规模和数量的增加 人们消费33，34，这往往受到学习经验和环境食品的影响- 相关线索可能会驱使一个人在代谢/能量之外进食，这需要10，11。 我们的实验室4，5表明腹侧海马(CA1v)向下丘脑外侧的投射具有重要作用 前额叶内侧区(LHA)和内侧前额叶皮质(MPFC)在调节条件摄食和动机摄食方面的作用 行为。然而，CA1v的神经通路和行为机制与食物的整合有关 内部和环境线索没有得到充分的表征。这项提议的目标是[1]绘制主要地图 CA1v神经元的一阶投影，[2]识别从CA1v；mPFC和mPFC分支的侧支通路 和[3]确定CA1v；mPFC和CA1v；LHA的二阶投影输出 路径(目标I)。该提案还旨在测试CA1v；mPFC和CA1v；LHA的功能相关性 通过病毒介导的CA1v通路的断开与 与啮齿动物摄食相关的行为范式：探索与内外相关的记忆过程 与摄食有关的提示(AIM II)。总体建议的实验评估多个层次的分析和利用 最先进的方法，包括条件性病毒发生神经通路追踪和功能 化学遗传学方法解开将学习和记忆与进食行为联系起来的神经回路。

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.