Long-range and local connectivity of cholinergic interneurons in the nucleus accumbens

项目摘要 丘脑核（NAc）是控制奖励相关行为和动机行为的关键中心， 在药物成瘾和抑郁症等神经精神疾病中被破坏。NAc由一个 核心（NAcCore）和周围内侧壳（NAcMS），每个都整合了来自 一系列大脑区域。这些NAc亚区含有多种细胞，其中大多数是GABA能细胞， 胆碱能中间神经元（CINs）除外。通过乙酰胆碱的释放，CIN可以有力地 调制本地网络以影响NAc的输出。然而，CINs接收和处理的能力 不同的长程兴奋性输入在NAc中基本上是未开发的。为了理解 正常和病理行为，有必要研究在NAc中CIN的突触组织， 分区域和具体投入方式。在这里，我使用了病毒追踪方法，切片电生理学， 和光遗传学在转基因小鼠中建立Nac中CIN的突触组织。目标1将确定 在NAcMS和NAcCore中，哪些脑区域和局部纹状体细胞突触到CIN上。目标2将 评估不同类型的远程输入如何接触和影响每个北大西洋公约组织分区域的信息网络干扰发射。 目的3将测试不同的GABA能中间神经元如何介导CINs的前馈抑制以调节它们的功能。 活动总之，这些实验将提供关键的洞察到突触组织的CIN内， 以及不同的输入如何驱动独特的活动模式。这项工作是必要的了解如何 NAc整合了包含动机驱动、奖励价值和 注意力，以及最终如何在神经精神疾病中破坏这个关键的奖励中心的电路。

PROJECT SUMMARY The nucleus accumbens (NAc) is a critical center for controlling reward-related and motivated behaviors, and becomes disrupted in neuropsychiatric disorders such as drug addiction and depression. The NAc consists of a core (NAcCore) and surrounding medial shell (NAcMS), each of which integrates distinct excitatory inputs from a wide range of brain areas. These NAc subregions contain a variety of cells, most of which are GABAergic, with the exception of cholinergic interneurons (CINs). Through the release of acetylcholine, CINs can powerfully modulate the local network to impact the output of the NAc. However, the ability of CINs to receive and process different long-range excitatory inputs is largely unexplored in the NAc. To understand the circuit mechanisms of normal and pathological behavior, it is necessary to study the synaptic organization of CINs in the NAc in a subregion- and input-specific manner. Here I use a combination of viral tracing methods, slice electrophysiology, and optogenetics in transgenic mice to establish the synaptic organization of CINs in the NAc. Aim 1 will identify which brain regions and local striatal cells synapse onto CINs in both the NAcMS and NAcCore. Aim 2 will assess how different types of long-range inputs contact and influence the firing of CINs in each NAc subregion. Aim 3 will test how different GABAergic interneurons mediate feed-forward inhibition of CINs to regulate their activity. Together, these experiments will provide critical insights into the synaptic organization of CINs within the NAc and how different inputs drive unique patterns of activity. This work is necessary for understanding how the NAc integrates converging inputs containing information about motivational drive, reward value, and attention, and ultimately how the circuitry of this key reward center is disrupted in neuropsychiatric disorders.