Physiology and function of basal ganglia subcircuits in sequence learning

序列学习中基底神经节亚电路的生理学和功能

基本信息

批准号：
8656825
负责人：
Xin Jin
金额：
$ 42.01万
依托单位：
SALK INSTITUTE FOR BIOLOGICAL STUDIES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8656825
关键词：
Basal Ganglia Behavior Behavioral Cell Nucleus Cells Corpus striatum structure Deltastab Development Disease Dissection Electrodes Electrophysiology (science)Functional disorder Genetic Globus Pallidus Goals Human Huntington Disease Individual Intervention Investigation Laboratory Animals Lead Learning Medial Mental disorders Modeling Molecular Molecular Biology Movement Mus Neural Pathways Neurons Obsessive-Compulsive Disorder Operant Conditioning Organism Output Parkinson Disease Partner in relationship Pathway interactions Patients Performance Physiological Physiology Process Property Reproduction Rewards Series Structure of subthalamic nucleus Study models Substantia nigra structure Symptoms Task Performances Techniques Testing Time Training Update Work base cell type in vivo insight interest knockout gene learned behavior nervous system disorder neural circuit novel optogenetics prevent public health relevance receptor research study sequence learning task analysis theories tool

项目摘要

DESCRIPTION (provided by applicant): The organism's behaviors are usually organized as action sequences. Sequence learning and execution serve as a wide range of abilities for the organism's survival and reproduction, from predating, mating to communicating. The basal ganglia have been suggested to be critically involved in learning and performance of action sequences. However, the molecular and circuit mechanisms underlying these processes remain largely uncovered. The current theory about basal ganglia function suggests that there are two major neural pathways, the striatonigral (direct) vs. striatopallidal (indirect) pathway, that workin an antagonistic manner to facilitate and inhibit movements respectively. Although this working hypothesis has been applied to basal ganglia function and related diseases for many years, this classic model has not been directly evaluated through experiments and thus it remains unclear if it's correct. The present project will systemically investigate the physiology and function of te striatonigral vs. striatopallidal subcircuit during learning and execution of action sequences. A combination of different techniques including operant conditioning, behavioral microstructure analysis, in vivo electrophysiology, genetic and optogenetic tools will be utilized to dissect the basal ganglia subcircuits in behaving mice. A novel action sequence training paradigm will be developed in mice and in vivo multiple-electrode neuronal recording will be performed during the performance of the task. Based on the analysis of behavioral microstructure, the sequence-related neuronal activity in the different nuclei of basal ganglia circuits will be established and compared. Cell types will be identified in vivo through optogenetic activation, followed by optogenetic manipulation experiments to define the cell-type and pathway- specific function of the striatonigral vs. striatopallidal subcircuit in sequence behavior. Together the project aims to physiologically and functionally revisit the classic working model of basal ganglia pathways.

描述（由申请人提供）：生物体的行为通常被组织为动作序列。序列学习和执行是有机体生存和繁殖的广泛能力，从捕食、交配到交流。基底神经节被认为在动作序列的学习和执行中发挥着重要作用。然而，这些过程背后的分子和电路机制仍然很大程度上未被揭示。目前关于基底神经节功能的理论表明，有两种主要的神经通路，即纹状体黑质（直接）通路和纹状体苍白球（间接）通路，它们以拮抗的方式分别促进和抑制运动。尽管这一工作假设已应用于基底神经节功能和相关疾病多年，但这一经典模型尚未通过实验直接评估，因此尚不清楚其是否正确。本项目将系统地研究在学习和执行动作序列期间纹状体黑质与纹状体苍白球亚回路的生理学和功能。包括操作条件反射、行为微观结构分析、体内电生理学、遗传和光遗传学工具在内的不同技术的组合将被用来剖析行为小鼠的基底神经节亚回路。将在小鼠中开发一种新的动作序列训练范例，并在执行任务期间进行体内多电极神经元记录。基于行为微观结构分析，建立基底神经节环路不同核团中序列相关的神经元活动，并比较的。将通过光遗传学激活在体内鉴定细胞类型，然后通过光遗传学操作实验来定义序列行为中纹状体黑质与纹状体苍白球亚回路的细胞类型和通路特异性功能。该项目的共同目标是从生理和功能上重新审视基底神经节通路的经典工作模型。