ALCOHOL REGULATION OF KAPPA OPIOID RECEPTOR SYSTEMS IN THE EXTENDED AMYGDALA

描述(由申请人提供)：酒精使用障碍是一个主要的公共卫生问题，到目前为止，还没有全面的治疗或干预措施。终纹床核(BNST)参与整合皮层和皮质下的输入，协调行为反应，并与酒精使用和滥用以及应激相关行为有关。Kappa阿片受体(KOR)已经在BNST中被证明可以改变神经递质信号[1]，尽管它对谷氨酸能传递的影响尚未被证实。 将被澄清。这个项目的目标是对Kors在BNST中谷氨酸能信号转导中的作用进行彻底的研究和表征，以及这种联系是如何被酒精依赖模型改变的。为了完成第一个目标，我将使用切片电生理学来评估BNST中谷氨酸能Kors的功能、信号和定位。为了完成第二个目标，我将结合光遗传学、慢性间歇性乙醇暴露和切片电生理学来评估Kors如何在乙醇暴露前后调节通路特异性的BNST输入。因此，这项提案将使用创新方法的组合来提供全面和收敛的证据，以表征KOR对BNST中谷氨酸能传递的调节。

DESCRIPTION (provided by applicant): Alcohol use disorders represent a major public health problem, and to date, no comprehensive treatment or intervention is available. The Bed Nucleus of the Stria Terminalis (BNST) is involved in integrating cortical and subcortical inputs to orchestrate behavioral responses, and has been implicated in alcohol use and abuse, as well as stress related behaviors. The kappa opioid receptor (KOR) has been demonstrated in the BNST to alter neurotransmitter signaling [1], though its effect on glutamatergic transmission has yet to be elucidated. The goals of this project are to conduct a thorough investigation and characterization into the role of KORs on glutamatergic signaling in the BNST, and how this connection is altered by a model of alcohol dependence. To complete the first aim, I will use slice electrophysiology to evaluate the function, signaling, and locus of glutamatergic KORs in the BNST. To complete this second aim, I will use a combination of optogenetics, chronic-intermittent ethanol exposure, and slice electrophysiology to assess how KORs modulate pathways- specific inputs to the BNST both before and after ethanol exposure. Thus, this proposal will use a combination of innovative approaches to provide thorough and convergent evidence characterizing KOR modulation of glutamatergic transmission in the BNST.