Electrophysiology of alcohol in extended amygdala

描述（由申请人提供）：此补充资金的修订申请是对通知编号（NOT-OD-09-058）和通知标题的回应：NIH宣布竞争性修订申请的恢复法案资金可用性。本申请所源自的母体INIA West U 01是基于行为发现，即中央杏仁核（CeA）是导致应激反应和滥用药物强化特性的关键脑区，并且这些行为涉及几种CeA递质（GABA，谷氨酸）和神经肽（CRF，阿片类药物和甘丙肽）。我们假设，这些神经化学系统在CeA参与了过度饮酒依赖动物。我们对CeA神经元中这些系统的电生理学研究已经发表（CRF 1，mu和delta阿片受体的作用）或正在进行（κ阿片和甘丙肽受体的作用）。然而，由于INIA West最近表示需要开始对INIA West的分子组分所建议的参与过量饮酒的基因产物的功能进行生理学评价，我们提出了该应用的新研究。具体而言，我们将使用电生理学方法来研究由Y. Blednov研究U 01（脂多糖{LPS}，TLR 4，CD 14，细胞因子）在酒精相关方面的神经元功能的CeA。为此，我们将在体外脑切片中使用电生理记录方法，并检查LPS，乙醇和CRF对野生型和CD 14敲除小鼠CeA神经元中GABA能和谷氨酸能传递的相互作用。因此，这些拟议的新研究代表了评估其他INIA West组件所建议的新兴基因靶点的细胞位点和作用机制的新的早期步骤，这些靶点是酒精偏好或过度饮酒的基础。此外，通过这次申请，我们也试图保留我们的高级博士后研究员的工作，并允许我们的高级技术人员全力以赴。

DESCRIPTION (provided by applicant): This revision application for supplemental funds is in response to Notice Number (NOT-OD-09-058) and Notice Title: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications. The parent INIA West U01 from which this application is derived is based on behavioral findings that the central amygdala nucleus (CeA) is a key brain area underlying stress reactions and the reinforcing properties of abused drugs, and that these behaviors involve several CeA transmitters (GABA, glutamate) and neuropeptides (CRF, opioids and galanin). We hypothesized that these neurochemical systems in the CeA are involved in the excessive ethanol drinking seen in dependent animals. Our electrophysiological studies of these systems in CeA neurons are either published (the role of CRF1, mu and delta opioid receptors) or ongoing (role of kappa opioid and galanin receptors). However, due to the recently stated need of the INIA West to begin physiological evaluation of the function of gene products suggested by the molecular components of the INIA West to be involved in excessive alcohol drinking, we propose the new studies of this application. Specifically, we will use electrophysiological methods to investigate the cellular role of the inflammatory factors identified by the Y. Blednov Research U01 (lipopolysaccharide {LPS}, TLR4, CD14, cytokines) in alcohol-related aspects of neuronal function in the CeA. Toward this aim we will use electrophysiological recording methods in brain slices in vitro and examine the interactions of LPS, ethanol and CRF on GABAergic and glutamatergic transmission in CeA neurons of wild type and CD14 knockout mice. These proposed new studies thus represent the new early steps toward evaluating the cellular sites and mechanisms of action of the emerging gene targets suggested by other INIA West components to underlie alcohol preference or excessive drinking. In addition, with this application we also are attempting to retain the job of our senior postdoctoral researcher and to allow full effort from our senior technician.