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：
10443838
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/10443838
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.

项目摘要酒精使用障碍（AUDS）带来了巨大的财务（超过2500亿美元）和社会压力。为了因此，开发药物和行为疗法以治疗auds，重要的是要了解在过渡到饮酒过量的过渡中发生的神经回路和神经适应。该应用的重点放在神经素（NTS）神经元的群体上（CEA）。利用遗传性，CRE成年酶策略以及选择性病变（CASPASE3）和光遗传学（通道视紫红素）策略，我们发现这些神经元通过其项目到副核（PBN），调节酒精的过量消耗和奖励样的行为。在这个提案我们假设NTSCEA和NTSCEA中的GABA能信号传导奖励和乙醇消耗行为。我们将在3个融合目标上探讨这一假设。目标1 将探讨NTSCEA神经元中信号分子在奖励，饮酒和食欲。 AIM 2将进一步探测NTSCEA内GABA能信号传导的作用。最后，AIM 3将探索这些电路中的身体适应。这些目标在一起提供了创新框架以辨别大脑内部特定项目如何影响奖励行为和饮酒。