Probing central amygdala neurotensin neurons in alcohol consumption

探索饮酒中的中央杏仁核神经降压素神经元

基本信息

批准号：
10256053
负责人：
Zoe Anastasia McElligott
金额：
$ 39.71万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10256053
关键词：
Ablation Acute Alcohol consumption Alcohols Amygdaloid structure Animal Model Appetitive Behavior Behavior Behavior Therapy Behavioral Brain Cell Nucleus Cells Chronic Consumption Coupled Data Desire for food Development Dose Electrophysiology (science)Enterobacteria phage P1 Cre recombinase Ethanol Exhibits Functional disorder Genetic Heavy Drinking Human Lateral Lesion Liquid substance Measures Medial Mediating Medical Neurons Neuropeptides Neurotensin Optics Pathologic Pathway interactions Pharmacology Physiological Adaptation Physiology Play Population Regulation Rewards Rhodopsin Role Shapes Signal Transduction Signaling Molecule Slice Stream Synapses Technology Testing Viral alcohol behavior alcohol exposure alcohol reward alcohol seeking behavior alcohol testing alcohol use disorder anxiety-like behavior cell type drinking experience gamma-Aminobutyric Acid innovation knock-down neural circuit neuroadaptation neuronal circuitry optogenetics parabrachial nucleus response small hairpin RNA social synaptic function transmission process vesicular GABA transporter

项目摘要

Project Summary Alcohol use disorders (AUDs) impart a huge financial (in excess of $250 billion) and societal strain. In order to develop pharmacological and behavioral therapies to treat AUDs, therefore, it is important to understand the neural circuitry and neuroadaptation that occurs in the transition to excessive consumption of alcohol use. The focus of this application is on a population of neurotensin (NTS) neurons the central nucleus of the amygdala (CeA). Utilizing genetic, cre-recombinase strategies in conjunction with selective lesioning (caspase3) and optogenetic (channel rhodopsin) strategies, we have found that these neurons, via their projections to the parabrachial nucleus (PBN), regulate both excessive consumption of alcohol, and reward-like behaviors. In this proposal we hypothesize that GABAergic signaling within the NTSCeA and in the NTSCeAPBN mediates reward and ethanol consumption behaviors. We will explore this hypothesis over 3 converging aims. Aim 1 will probe the role of signaling molecules within NTSCeA neurons on reward, alcohol consumption and appetitive behavior. Aim 2 will further probe the role of GABAergic signaling within the NTSCeAPBN projection. Finally, Aim 3 will explore physiological adaptation within these circuits. Together, these aims provide an innovative framework to discern how specific projections within the brain are influencing the reward behavior and consumption of alcohol.

项目概要酒精使用障碍 (AUD) 造成巨大的财务（超过 2500 亿美元）和社会压力。开发药物和行为疗法来治疗 AUD，因此，了解 AUD 的治疗方法非常重要过度饮酒过渡过程中发生的神经回路和神经适应。该应用的重点是杏仁核中央核的神经降压素 (NTS) 神经元群 (CeA)。利用遗传、cre 重组酶策略与选择性损伤 (caspase3) 相结合。光遗传学（视紫质通道）策略，我们发现这些神经元通过它们的投射到臂旁核（PBN），调节过量饮酒和奖励样行为。我们提出的建议是 NTSCeA 和 NTSCeAPBN 中的 GABAergic 信号传导我们将通过 3 个目标 1 来探讨这一假设。将探究 NTSCeA 神经元内信号分子对奖赏、饮酒和目标 2 将进一步探讨 GABAergic 信号在 NTSCeAPBN 投影中的作用。最后，目标 3 将探索这些回路中的生理适应，这些目标共同提供了一个目标。创新框架来辨别大脑内的特定投射如何影响奖励行为和饮酒。