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Role of novel VTA neurons in addiction-related behaviors

新型 VTA 神经元在成瘾相关行为中的作用

基本信息

批准号：
10611404
负责人：
Thomas Hnasko
金额：
$ 42.53万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
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：
2014-04-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10611404
关键词：
Adult Amino Acid Neurotransmitters Anabolism Anatomy Animals Basal Ganglia Behavior Behavior Control Behavioral Biological Assay CRISPR/Cas technology Cell Nucleus Cells Clustered Regularly Interspaced Short Palindromic Repeats Complex Development Disease Distal Dopamine Drug Addiction Drug Targeting Electron Microscopy Electrophysiology (science)Future Genetic Globus Pallidus Glutamates Goals Habenula Heterogeneity Image Interneurons Intervention Label Lateral Learned Helplessness Limbic System Link Maps Mediating Membrane Potentials Mus Negative Reinforcements Neuromodulator Neurons Pathway interactions Population Positioning Attribute Positive Reinforcements Process Psychological reinforcement Recycling Research Rewards Role Selective Serotonin Reuptake Inhibitor Shapes Signal Transduction Site Testing Ventral Striatum Ventral Tegmental Area addiction cell type dopaminergic neuron drug abuse prevention drug of abuse frontal lobe gamma-Aminobutyric Acid genetic approach light microscopy motivated behavior neural circuit neuropsychiatric disorder neurotransmission novel optogenetics postsynaptic postsynaptic neurons programs targeted treatment

项目摘要

PROJECT SUMMARY The ventral tegmental area (VTA) is a core component of the neural circuitry that drives goal-directed behavior, and a primary target through which drugs of abuse modulate behavior. Although generally regarded as a dopaminergic nucleus, about half of VTA neurons signal through release of the amino acid neurotransmitters GABA and glutamate. These neurons are also targets of drugs of abuse but much less studied. Recent evidence from our lab and others has begun to show that, like VTA DA neurons, activity in VTA GABA and glutamate neurons can profoundly shape motivated behaviors. Furthermore, sub-populations of VTA neurons release more than one of these three recycling transmitters, including neurons that co-release dopamine and glutamate, or glutamate and GABA. The goals of this proposal are to identify how transmitter co-release from VTA contributes to the processes underlying behavioral reinforcement, and how co-releasing neurons functionally integrate into the mesolimbic neural circuits that regulate motivated behavior. We will use an array of genetic approaches in combination with behavioral, anatomical, and electrophysiological assays in mice to selectively probe the connectivity and function of discrete VTA circuits. Together this continuing research program comprises a thorough plan to define the form and function of novel classes of VTA neurons and enhance our understanding of how intrinsic VTA heterogeneity shapes behaviors relevant to neuropsychiatric disease.

项目摘要腹侧被盖区（VTA）是驱动目标导向行为的神经回路的核心组成部分，也是滥用药物调节行为的主要目标。虽然一般被认为是在多巴胺能神经核中，大约一半的腹侧被盖区神经元通过释放氨基酸神经递质发出信号 GABA和谷氨酸。这些神经元也是滥用药物的目标，但研究得很少。最近的证据来自我们实验室和其他人的研究已经开始表明，与腹侧被盖区DA神经元一样，腹侧被盖区GABA和谷氨酸的活动神经元可以深刻地塑造动机行为。此外，腹侧被盖区神经元的亚群释放更多的比这三种回收递质之一更有效，包括共同释放多巴胺和谷氨酸的神经元，或者谷氨酸和GABA。本提案的目标是确定VTA中的发射器共同释放如何发挥作用行为强化背后的过程，以及共同释放神经元如何在功能上整合到调节动机行为的中脑边缘神经回路。我们将使用一系列遗传学方法，结合小鼠中的行为、解剖和电生理测定，以选择性地探测离散VTA电路的连接和功能。这项持续的研究计划包括一个一个彻底的计划，以定义VTA神经元的新类别的形式和功能，并提高我们的理解内在VTA异质性如何塑造与神经精神疾病相关的行为。