The role of a nucleus tractus solitarius-central amygdala circuit in alcohol-induced plasticity and drinking behavior

酒精中毒是一种复杂的疾病，其特征是特定大脑区域和回路的神经适应性变化。 会导致与酒精依赖相关的不良行为后果。此前的研究主要集中在 中央杏仁核(CEA)在延伸杏仁核中的作用，CEA与其他脑的联系 地区也可以影响CEA的响应性，最终改变行为。形成互惠关系的一个地区 与CEA的联系是孤束核(NTS)。NTS接受来自 作为一个综合的自主神经中心。CEA将情感关联赋予内部和 外部感官输入。因此，ntsCEA电路代表了一条潜在的管道，通过该管道，外围状态 会影响情绪反应，情绪状态会影响外周功能。在这方面，NTS CEA回路也可能是急性和慢性乙醇的一个重要靶点，也是一个未被充分研究的来源 改变饮酒行为的回路功能障碍。这项提案的总体目标是采用一种联合的 电生理、分子和行为方法，使用光遗传学和 检测NTS微电路、NTS神经元对酒精暴露的敏感性及其作用的化学遗传学 NTSCEA环路在饮酒行为和酒依赖形成中的作用。分子和 电生理学研究将用于确定NTS微电路的不同组件以及 体外急性乙醇和体内慢性乙醇对NTS环路成分突触传递和活动的影响。 将使用逆行追踪、电生理、光遗传学和化学遗传学研究来识别特定的 以确定慢性酒精对和CEA的影响 蜂窝和电路级别的特定组件。自愿性酒精的化学遗传学和行为学研究 消费将被用来评估ntsCEA回路在饮酒中的作用。总的来说，这些研究 将提供有关nts和ntsCEA电路在细胞和电路中的作用的新信息。 酒精依赖的潜在机制。

Alcoholism is a complex disorder characterized by neuroadaptive changes in specific brain regions and circuits that promote adverse behavioral outcomes associated with alcohol dependence. Previous studies have focused on the role of the central amygdala (CeA) in the extended amygdala, however, CeA connections with other brain regions can also influence CeA responsivity to ultimately alter behavior. One region that forms reciprocal connections with the CeA is the Nucleus Tractus Solitarius (NTS). The NTS receives sensory input from the periphery and acts as an integrative autonomic center. The CeA confers emotional relevance to internal and external sensory input. Thus, the NTS  CeA circuit represents a potential conduit by which peripheral state can influence emotional reactivity and emotional state can impact peripheral function. In that context, the NTS CeA circuit may also represent an important target for acute and chronic ethanol and an understudied source of circuit dysfunction that alters drinking behavior. The overarching goal of this proposal is to employ a combined electrophysiological, molecular, and behavioral approach with functional circuit mapping using optogentics and chemogenetics to examine NTS microcircuitry, the sensitivity of NTS neurons to ethanol exposure, and the role of the NTSCeA circuit in drinking behavior and the development of alcohol dependence. Molecular and electrophysiological studies will be used to identify distinct components of NTS microcircuitry and the impact of acute in vitro and chronic in vivo ethanol on synaptic transmission and activity in NTS circuit components. Retrograde tracing, electrophysiological, optogenetic, and chemogenetic studies will be used to identify specific components of the NTS CeA circuit in the NTS and CeA to determine the impact of chronic ethanol on these specific components at a cellular and circuit level. Chemogenetic and behavioral studies of voluntary ethanol consumption will be used to assess the role of the NTS CeA circuit in drinking. Collectively, these studies will provide new information on the role of the NTS and the NTS CeA circuit in the cellular and circuit mechanisms underlying ethanol dependence.