The Role of Striatonigrostriatal Circuitry in Habit Formation

纹状体黑质纹状体回路在习惯形成中的作用

基本信息

批准号：
8926702
负责人：
Talia Newcombe Lerner
金额：
$ 3.38万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-04-13
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8926702
关键词：
Address Anatomy Animals Area Basal Ganglia Behavioral Brain Brain region Cell Nucleus Cells Complex Compulsive Behavior Corpus striatum structure Cues Detection Disease Dopamine Drug Addiction Drug abuse Electrophysiology (science)Elements Feedback Fiber Optics Fluorescence Foundations Functional disorder Future Goals Habits Health Human Implant Indium Knowledge Lead Learning Liquid substance Maps Measures Mediating Mental disorders Modeling Monkeys Neurons Obsessive-Compulsive Disorder Output Pattern Photometry Physiology Play Process Property Rabies Research Rodent Role Services Signal Transduction Slice Specific qualifier value Staging Structure Substantia nigra structure Synapses Synaptic plasticity System Techniques Technology Testing Tracer Viral Work addiction area striata base calcium indicator dopamine system dopaminergic neuron drug relapse in vivo insight interest neural circuit neuromechanism optogenetics public health relevance response

项目摘要

DESCRIPTION (provided by applicant): Habits allow for the fast, fluid, nearly effortless execution of complex tasks, yet they can also be detrimental, for example in cases where they lead to compulsive behaviors such as in obsessive-compulsive disorder (OCD) or to behavioral patterns of drug abuse and relapse in addiction. Habit formation requires two reciprocally connected brain areas: the striatum, the input nucleus of the Basal Ganglia, and the substantia nigra (SN), which provides modulatory dopaminergic signals to the striatum. Decades of research on humans, monkeys and rodents have shown that different regions of striatum have different roles in habit formation. Initial task acquisition, which is goal-directed, is mediated b the dorsomedial striatum, while habit formation is mediated by the dorsolateral striatum. How can these two regions of striatum, which are very similar in their gross physiology and anatomy, support these two very different behavioral modes? One hypothesis, explored in this proposal, is that the connectivity motifs - the specific relationships between the inputs and the outputs - o the striatum and the SN differ by region. The long-term objective of this research will be to establish a functional input-output connectivity map of SN dopamine neurons that elucidates the diverse projection-specific functions of these neurons as an animal undergoes habit formation. In service of this overarching objective, three specific, immediately achievable aims are proposed, each of which is made possible by a recently developed technological approach. The approaches are (1) TRIO, a rabies-based circuit mapping technology that allows the simultaneous study of the inputs and outputs of a brain region of interest, (2) slice electrophysiology in combination with optogenetics, allowing for functional circuit mapping and (3) in vivo photometry, permitting the detection of calcium indicator fluorescence from subsets of SN dopamine neurons defined by their output in order to measure the activity of specific circuit elements in freely behaving animals. Together, these approaches will yield new insights into the structure and function of striatonigrostriatal circuit elements during the process of habit formation.

描述（由申请人提供）：习惯允许快速，流动，几乎毫不费力地执行复杂的任务，但它们也可能有害，例如，在导致强迫性行为（例如强迫症（OCD）中）或对吸毒的行为滥用和成瘾中的复发模式。习惯形成需要两个相互连接的大脑区域：纹状体，基底神经节的输入核和底底nigra（SN），该（SN）为纹状体提供了调节性多巴胺能信号。数十年来对人类，猴子和啮齿动物的研究表明，纹状体的不同区域在习惯形成中具有不同的作用。最初的任务采集是指向目标指导的，是在背侧纹状体中介导的，而习惯形成是由背外侧纹状体介导的。这两个纹状体的这两个区域如何在其总体生理和解剖结构中非常相似，支持这两种截然不同的行为模式？在本提案中探讨的一个假设是，连通性基序 - 输入与输出之间的特定关系 - 纹状体和SN因区域而不同。这项研究的长期目标是建立SN多巴胺神经元的功能输入输出连接图，该图阐明了这些神经元作为动物的多种投影特异性功能会经历习惯形成。为了为这个总体目标服务，提出了三个特定的，可立即实现的目标，每种目标都是通过最近开发的技术方法使其成为可能的。 The approaches are (1) TRIO, a rabies-based circuit mapping technology that allows the simultaneous study of the inputs and outputs of a brain region of interest, (2) slice electrophysiology in combination with optogenetics, allowing for functional circuit mapping and (3) in vivo photometry, permitting the detection of calcium indicator fluorescence from subsets of SN dopamine neurons defined by their output in order to measure the activity of specific自由表现动物的电路元素。这些方法一起，将在习惯形成过程中对纹状体式纹状体电路元素的结构和功能产生新的见解。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain.

DOI：
10.1038/nmeth.3770
发表时间：
2016-04
期刊：
Nature methods
影响因子：
48
作者：
Kim CK;Yang SJ;Pichamoorthy N;Young NP;Kauvar I;Jennings JH;Lerner TN;Berndt A;Lee SY;Ramakrishnan C;Davidson TJ;Inoue M;Bito H;Deisseroth K
通讯作者：
Deisseroth K

Nucleus accumbens D2R cells signal prior outcomes and control risky decision-making.