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

• 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
• 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

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（AUD）带来了巨大的经济（超过2500亿美元）和社会压力。为了 开发药物和行为疗法来治疗AUDs，因此，重要的是要了解 神经回路和神经适应发生在过渡到过度消费酒精使用。的 本申请的焦点在于杏仁核中央核的神经降压素（NTS）神经元群 （CeA）。利用遗传、cre-重组酶策略结合选择性损伤（半胱天冬酶3）， 光遗传学（通道视紫红质）的策略，我们已经发现，这些神经元，通过他们的投射到 臂旁核（PBN），调节过度饮酒和奖励样行为。在这 我们假设NTSCeA内和NTSCeA内的GABA能信号传导介导了 奖励和乙醇消费行为。我们将通过3个趋同目标来探讨这一假设。要求1 将探索NTSCeA神经元内信号分子在奖励，饮酒和 食欲行为目的2将进一步探讨GABA能信号在NTSCeA → PBN投射中的作用。 最后，目标3将探索这些回路中的生理适应。总之，这些目标提供了一个 一个创新的框架来辨别大脑中的特定投射如何影响奖励行为 和饮酒。