Unbiased analysis of molecular and circuit targets of low dose alcohol

众所周知，酒精可以调节多种分子靶点，导致细胞内 突触功能和回路活动。这方面的大部分工作都集中在相对较高的酒精含量上 浓度，留下了关于低剂量酒精的分子和回路靶标的知识空白。 这是一个关键的话题，因为机械地理解这些高度敏感的目标可以提供一个 有机会探索酒精最初是如何影响大脑的。因为关于神经元的数据有限 对低剂量酒精敏感的电路，我们选择主要无偏见地解决这个问题 解剖学方法。具体地说，利用多个实验室的专业知识，我们将利用 边缘分子方法及其在全脑活体成像中的研究进展 对低剂量酒精敏感的保守的神经元回路和分子靶点。然后我们将使用 测试这些电路和分子在调节对Low的敏感性中的因果作用的收敛方法 过量饮酒。因此，将这些目标放在一起，将提供一个前所未有的机会来确定 (目标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.