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

伏隔核中胆碱能中间神经元的远程和局部连接

• 批准号: 10389463
• 负责人: Emily Jang
• 金额: $ 3.87万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-10 至 2024-12-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10389463
• 关键词: Acetylcholine; Address; Amygdaloid structure; Anatomy; Area; Attention; Behavior; Brain; Brain region; Cells; Complement; Corpus striatum structure; Disease; Distant; Dopamine; Dorsal; Drug Addiction; Electrophysiology (science); Glutamates; Goals; Hippocampus (Brain); Immunohistochemistry; Interneurons; Learning; Medial; Mediating; Mental Depression; Methods; Microscopy; Motivation; Neurons; Nucleus Accumbens; Output; Parvalbumins; Pathologic; Pattern; Play; Population; Prefrontal Cortex; Process; Property; Rabies; Rewards; Role; Shapes; Signal Transduction; Slice; Somatostatin; Stimulus; Surveys; Synapses; Testing; Thalamic structure; Transgenic Mice; Translating; Ventral Striatum; Viral; Virus; Work; brain reward regions; cell type; cholinergic; experimental study; insight; motivated behavior; motivational processes; neuronal cell body; neuropsychiatric disorder; optogenetics; rabies viral tracing; response

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.

项目概要 伏隔核 (NAc) 是控制奖励相关和动机行为的关键中心，并且 因药物成瘾和抑郁症等神经精神疾病而受到干扰。 NAc 包含一个 核心（NAcCore）和周围的内侧壳（NAcMS），每个都集成了不同的兴奋性输入 广泛的大脑区域。这些 NAc 亚区包含多种细胞，其中大部分是 GABA 能细胞， 胆碱能中间神经元（CIN）除外。通过释放乙酰胆碱，CINs 可以强有力地 调制本地网络以影响 NAc 的输出。然而，CIN 接收和处理的能力 不同的长程兴奋性输入在 NAc 中很大程度上尚未被探索。了解电路机制 正常和病理行为，有必要研究 NAc 中 CIN 的突触组织 分区域和投入特定的方式。这里我结合了病毒追踪方法、切片电生理学、 以及转基因小鼠中的光遗传学，以建立 NAc 中 CIN 的突触组织。目标 1 将确定 大脑区域和局部纹状体细胞突触到 NAcMS 和 NAcCore 中的 CIN。目标2将 评估不同类型的远程输入如何接触并影响每个 NAc 分区中 CIN 的发射。 目标 3 将测试不同的 GABA 能中间神经元如何介导 CIN 的前馈抑制以调节其 活动。总之，这些实验将为 CIN 的突触组织提供重要的见解。 NAc 以及不同的输入如何驱动独特的活动模式。这项工作对于理解如何 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回路在神经精神疾病中是如何被破坏的。