Isolation of brain reward circuits using peptidergic systems

使用肽能系统分离大脑奖励回路

基本信息

批准号：
9882989
负责人：
LARRY S ZWEIFEL
金额：
$ 34.02万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-15 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9882989
关键词：
3&apos Untranslated Regions Acute Address Anatomy Anxiety Asses Behavior Behavioral Brain CRISPR/Cas technology Code Corpus striatum structure Cre driver Cues Data Dependence Disease Disease susceptibility Dissection Dopamine Electrophysiology (science)Emotional Enterobacteria phage P1 Cre recombinase Enzymes Etiology Fright Functional disorder Genes Genetic Genetic Heterogeneity Genetic Techniques Glutamates Goals Heterogeneity Hypothalamic structure Internal Ribosome Entry Site Learning Limbic System Literature Maps Mediating Mental Depression Mental disorders Methods Midbrain structure Motivation Mus Neurons Neuropeptide Receptor Neuropeptides Neurotransmitters Nucleus Accumbens Output Pathway interactions Pattern Periodicity Play Population Post-Traumatic Stress Disorders Precision therapeutics Production Property Prosencephalon Rabies Regulation Rewards Role Scanning Schizophrenia Signal Transduction Slice Substance Use Disorder Symptoms Synapses System Techniques Testing Therapeutic Tyrosine 3-Monooxygenase Ventral Tegmental Area Viral autism spectrum disorder base cell type dopamine system dopaminergic neuron experimental study gain of function gamma-Aminobutyric Acid genetic approach in vivo insight loss of function motivational processes nerve supply nervous system disorder neuropsychiatric disorder novel novel strategies optogenetics receptor

项目摘要

Project Summary Dopamine neurons of the ventral tegmental area (VTA) provide essential modulatory signals to the forebrain limbic system and cortex to facilitate learning and motivational processes. Disruptions in dopamine signaling are broadly implicated in mental illness and likely contribute to a spectrum of behavioral dysfunction through distinct cortico-limbic pathways. The heterogeneity of dopamine neurons in the VTA has long been appreciated, but therapeutic strategies targeting the system are still based on a monolithic perspective. Recent advances in mapping the input/output relationships of distinct dopamine pathways have attempted to resolve the basic organization of the VTA, but have yielded little in the way of establishing how specialized subdivisions might be organized. Unraveling the basic anatomical and functional organization of the VTA is essential if precision therapeutics are to be achieved for treating specific behavioral dysfunctions. We hypothesized that the dopamine system in the VTA can be organized based on peptidergic modulation to gate information through specific output pathways. We have mapped the projections of dopamine neurons in the VTA that express distinct neuropeptide receptors and discovered a remarkable specialization of these outputs. Here we propose to establish the basic electrophysiological, anatomical, and behavioral function of these pathways using novel Cre driver mouse lines in combination with advanced techniques in viral-based circuit dissection. We will also establish novel methods for the genetic characterization of these subpopulations. Successful completion of our proposed aims will provide novel insight into the basic organization of the VTA dopamine system and establish a framework for cracking the dopamine code.

项目摘要腹侧盖区域（VTA）的多巴胺神经元为前脑提供必要的调节信号边缘系统和皮层促进学习和动机过程。多巴胺信号的破坏广泛涉及精神疾病，可能会导致通过行为功能障碍独特的皮质膜途径。 VTA中多巴胺神经元的异质性长期以来一直是值得赞赏的，但是针对系统的治疗策略仍基于单片的观点。最近的映射不同多巴胺途径的输入/输出关系的进步已尝试解决 VTA的基本组织，但几乎没有建立专业化的方式可能会组织细分。揭示VTA的基本解剖和功能组织是对于治疗特定行为功能障碍的治疗，必须实现精确治疗。我们假设VTA中的多巴胺系统可以基于肽吉尼的调制到栅极通过特定的输出途径信息。我们绘制了多巴胺神经元的投影表达不同神经肽受体并发现这些输出的显着专业化的VTA。在这里，我们建议建立这些基本的电生理，解剖和行为功能使用新型CRE驱动器鼠标线与基于病毒的电路中的高级技术结合使用的途径解剖。我们还将为这些亚群的遗传表征建立新的方法。成功完成我们提议的目标将为VTA的基本组织提供新颖的见解多巴胺系统并建立一个破解多巴胺代码的框架。