Deconstructing the role of central nucleus of the amygdala neurotensin neurons in alcohol reward and intoxication

描述(由申请人提供)：酒精使用障碍在美国具有巨大的社会和财政影响。此外，酒精是可预防死亡的第三大原因(Mokda等人，2004年)。阐明有助于酒精回报特性的神经元电路可能为治疗酒精使用障碍的治疗机制提供洞察。杏仁核中央核(CEA)已被证明在调节饮酒行为的各个方面发挥作用，然而，CEA是一个异质核，不同的遗传定义的人群可能以不同的方式参与与酒精相关的行为。这项建议旨在评估CEA神经降压素(NTS)神经元在使用尖端工具介导乙醇中毒和自我给药中的因果作用。我将进行免疫组织化学、行为学和电生理实验。特别是，我将研究后脑臂旁核(PBN)的投射，这一区域被认为在压力和焦虑中发挥主要作用。通过这项研究，我计划展示投射到PBN的CEA-NTS神经元对酒精和相关线索的反应被激活，并调节酒精的一些奖励特性。这些实验将发现可能导致酒精使用障碍的新的神经元电路和机制，并为这种病理的治疗提供未来的靶点。

DESCRIPTION (provided by applicant): Alcohol use disorders have an enormous societal and fiscal impact in the United States. Moreover, alcohol is the third leading cause of preventable death (Mokdad et al., 2004). Elucidating the neuronal circuitry that contributes to the rewarding properties of alcohol may provide insight into therapeutic mechanisms for treating alcohol use disorders. The central nucleus of the amygdala (CeA) has been shown to play a role in regulating various aspects of alcohol drinking behavior, however, the CeA is a heterogeneous nucleus where different genetically defined populations may contribute to ethanol related behaviors in different ways. This proposal aims to assess the causal role of CeA-neurotensin (NTS) neurons in mediating ethanol intoxication and self-administration using cutting edge tools. I will perform immunohistochemical, behavioral and electrophysiological experiments. In particular I will investigate the projection to the parabrachial nuclei (PBN) in the hindbrain, a region that is thought to play a major role in stress and anxiety. Through this research I plan to show that CeA-NTS neurons that project to the PBN are activated in response to alcohol and associated cues and mediate some of the rewarding properties of alcohol. These experiments will uncover new neuronal circuitry and mechanisms that may contribute to alcohol use disorders and allow for future targets for the treatment of this pathology.