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: 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
• 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

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.

项目总结