Probing central amygdala neurotensin neurons in alcohol consumption

项目摘要 酒精使用障碍(AUD)带来了巨大的经济压力(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，了解 过度饮酒过程中发生的神经回路和神经适应。这个 这一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重组酶策略结合选择性损伤(Caspase3)和 光遗传(通道视紫质)策略，我们发现这些神经元，通过它们的投射到 臂旁核(PBN)既调节过度饮酒，又调节奖赏行为。在这 我们假设NTSCeA和NTSCeAPBN中的GABA能信号介导 奖励和酒精消费行为。我们将通过三个趋同的目标来探索这一假设。目标1 将探索NTSCeA神经元内的信号分子在奖赏、酒精消费和 食欲的行为。AIM 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将探索这些回路内的生理适应。这些目标加在一起提供了一个 创新的框架，以辨别大脑中的特定投射如何影响奖励行为 和饮酒。

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.