Unbiased analysis of molecular and circuit targets of low dose alcohol

已经确定酒精可以调节多种分子靶点，从而导致 突触功能和电路活动。这方面的工作大部分集中在相对较高的酒精 在低剂量酒精的分子和电路靶点方面存在知识空白。 这是一个关键的话题，因为对这些高度敏感的目标的机械理解可以提供一个 有机会探索酒精最初是如何影响大脑的。由于神经元的数据有限， 电路对低剂量酒精敏感，我们选择主要使用无偏 解剖学方法。具体而言，利用多个实验室的专业知识，我们将利用切割 边缘分子方法和全脑在体成像的进展，以识别和询问高度 保守的神经回路和对低剂量酒精敏感的分子靶点。然后我们将使用 聚合的方法来测试这些电路和分子在调节对低敏感性方面的因果作用， 剂量酒精。因此，这些目标合在一起，将提供一个前所未有的机会， (Aims 1和2），并测试低剂量激活的大脑回路和分子的因果作用（目标3） 酒精

It has been well established that alcohol can modulate a variety of molecular targets resulting in changes in synaptic function and circuit activity. Much of this body of work has focused on relatively high alcohol concentrations, leaving a gap in knowledge regarding the molecular and circuit targets of low dose alcohol. This is a critical topic, as a mechanistic understanding of these highly sensitive targets can provide an opportunity to probe how alcohol initially impacts the brain. Because of the limited data on the neuronal circuits sensitive to low dose alcohol, we are electing to approach this problem using primarily unbiased anatomical approaches. Specifically, leveraging expertise of multiple laboratories, we will capitalize on cutting edge molecular approaches and advances in whole-brain in vivo imaging to identify and interrogate highly conserved neuronal circuits and molecular targets that are sensitive to low dose alcohol. We will then use converging approaches to test the causal role of these circuits and molecules in regulating sensitivity to low dose alcohol. Therefore, taken together, these aims will provide an unprecedented opportunity to identify (Aims 1 and 2) and test the causal role (Aim 3) of brain circuits and molecules that are activated by low dose alcohol.