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

项目总结 伏隔核(NAC)是控制奖赏相关行为和动机行为的重要中枢。 在药物成瘾和抑郁等神经精神障碍中受到干扰。NAC由一个 核心(NAcCore)和周围内侧壳(NAcMS)，每个都集成了来自 广泛的大脑区域。这些NAC亚区包含各种细胞，其中大多数是GABA能细胞， 胆碱能中间神经元(CINs)除外。通过释放乙酰胆碱，CINS可以强大地 调制本地网络以影响NAC的输出。然而，CIN的接收和处理能力 不同的远程兴奋性输入在NAC中很大程度上是没有探索的。要了解的电路机制， 在正常和病理行为中，有必要研究NAC内CINS的突触组织。 针对次区域和投入的方式。在这里，我结合使用病毒追踪方法，切片电生理学， 和光遗传学在转基因小鼠中建立NAC内CINs的突触组织。目标1将确定 在NAcMS和NAcCore中，哪些脑区和局部纹状体细胞与CIN突触。目标2将 评估不同类型的远程投入如何接触和影响每个新AC次区域的CIN的发射。 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，以调节其 活动。综上所述，这些实验将提供对CIN在脑内的突触组织的关键见解 NAC以及不同的输入如何驱动独特的活动模式。这项工作对于理解 NAC集成了包含有关动机驱动、奖励价值和 注意力，以及最终这个关键奖励中心的电路是如何在神经精神障碍中被扰乱的。

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.