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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：
10160467
负责人：
LARRY S ZWEIFEL
金额：
$ 11.77万
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/10160467
关键词：
3&apos Untranslated Regions Acute Address Anatomy 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.

项目总结