Ventral Hippocampus Circuits Underlying Conditioned Feeding Behavior

条件性进食行为背后的腹侧海马回路

基本信息

批准号：
9975147
负责人：
Clarissa Liu
金额：
$ 2.34万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2021-04-03
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9975147
关键词：
Ablation Acute Adolescent Adult Affect Anatomy Appetitive Behavior Atlases Behavior Behavioral Mechanisms Behavioral Paradigm Brain Brain region Calories Caspase Child Chronic Clozapine Communication Complex Consumption Cues Data Desire for food Development Discrimination Eating Feeding behaviors Food Goals Heart Diseases Hippocampus (Brain)Hunger Hyperphagia Hypothalamic structure Individual Injections Label Lateral Lateral Hypothalamic Area Lead Learning Ligands Link Maps Medial Mediating Memory Metabolic Methodology Methods Modeling Neural Pathways Neurobiology Neurons Non-Insulin-Dependent Diabetes Mellitus Obesity Obesity Epidemic Output Overweight Oxides Palate Pathway interactions Play Prefrontal Cortex Prevalence Procedures Public Health Publications Publishing Rattus Research Rewards Rodent Role Satiation Specific qualifier value Stimulus Stroke Synapses System Techniques Testing Time Tracer United States Viral anterograde transport base behavioral pharmacology cancer type comorbidity computerized data processing deprivation designer receptors exclusively activated by designer drugs experience experimental study feeding innovation memory process mortality neural circuit neural network neurobiological mechanism neurotransmission novel obesity treatment programs recombinase-mediated cassette exchange relating to nervous system

项目摘要

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.

7. 项目概要/摘要过去 30 年来，肥胖症流行病日益严重，超过三分之二的成年人患有肥胖症超重或肥胖，大约六分之一的儿童和青少年被认为患有肥胖症1,7。这肥胖患病率的惊人增加在很大程度上是由于膳食量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可以驱使个体进食超出代谢/能量需求的相关线索10,11。最近发表的文章来自我们的实验室4,5表明腹侧海马（CA1v）投射到下丘脑外侧的重要作用区域（LHA）和内侧前额叶皮层（mPFC）在调节进食的条件和动机方面行为。然而，CA1v 整合食物相关的神经通路和行为机制内部和环境线索尚未完全表征。该提案的目标是 [1] 绘制主要 CA1v 神经元的一阶投影，[2] 识别从 CA1v>mPFC 分支的侧支通路和 CA1v>LHA 通路，以及 [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 的功能相关性通过将病毒介导的 CA1v 通路断开与啮齿动物喂养相关的行为范式，探究与内部和外部相关的记忆过程与喂养相关的线索（目标 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，包括条件病毒发生神经通路追踪和功能化学遗传学方法揭示了将学习和记忆与进食行为联系起来的神经回路。