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.

项目摘要 伏隔核（NAC）是控制与奖励相关和动机行为的关键中心，并且 在药物成瘾和抑郁等神经精神疾病中被破坏。 NAC由 核心（NACCORE）和周围的内侧壳（NACM），每种壳都整合了不同的兴奋性输入 广泛的大脑区域。这些NAC子区域包含多种细胞，其中大多数是Gabaergic，带有 除胆碱能中间神经元（CIN）外。通过乙酰胆碱的释放，CIN可以有力地 调节本地网络以影响NAC的输出。但是，CIN接收和处理的能力 在NAC中，不同的远程兴奋性输入在很大程度上没有探索。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 子区域和特定于输入的方式。在这里，我使用病毒追踪方法的组合，切片电生理学， 转基因小鼠中的光遗传学，以建立NAC中CIN的突触组织。 AIM 1将确定 哪些大脑区域和局部纹状体细胞突触到NACM和NACCORE中的CIN。 AIM 2意志 评估不同类型的远程输入接触并影响每个NAC子区域中CIN的发射。 AIM 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。这些实验将共同提供有关CINS突触组织的关键见解 NAC以及不同输入如何驱动独特的活动模式。这项工作对于理解如何 NAC整合了包含有关动机驱动力，奖励价值和的信息的收敛意见 注意，最终如何在神经精神疾病中破坏这个关键奖励中心的电路。