Mechanisms of synaptic dopamine signaling in the control of behavior

突触多巴胺信号传导在行为控制中的机制

基本信息

批准号：
10206280
负责人：
Sharad Ramanathan
金额：
$ 52.67万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10206280
关键词：
Address Affect Animals Attention Behavior Behavior Control Behavioral Behavioral Genetics Brain Caenorhabditis elegans Calcium Cells Cognition DRD2 gene Data Desire for food Disease Dopamine Dopamine Receptor Drug Targeting Event Experimental Models Family Food Functional Imaging Functional disorder G-Protein-Coupled Receptors GABA-A Receptor Genetic Human Individual Interneurons Ion Channel Gating Ligand Binding Ligands Link Mediating Mental disorders Methods Microscopic Microscopy Molecular Molecular Genetics Movement Movement Disorders Nematoda Nervous system structure Neurobiology Neuromodulator Neurons Neurotransmitters Obsessive-Compulsive Disorder Optical Instrument Parkinson Disease Physiology Play Potassium Channel Process Property Receptor Signaling Regulation Research Rewards Role Schizophrenia Signal Transduction Speed Stereotyping Stimulus Synapses System TRP channel Techniques Transcript addiction base behavior change behavioral response cellular targeting design dopamine system dopaminergic neuron drug of abuse experimental study gene discovery in vivo innovation loss of function mutant nervous system disorder neural circuit neurochemistry neuropsychiatric disorder neuroregulation novel novel strategies optogenetics postsynaptic postsynaptic neurons presynaptic programs receptor response targeted treatment therapeutic target tool

项目摘要

The neuromodulator dopamine is important for many brain functions: loss of dopamine neurons causes movement disorders, such as Parkinson’s disease; dopamine signaling is targeted by drugs of abuse and integral to the neurobiology of reward and addiction; and dopamine signaling is a therapeutic target for the treatment of many neuropsychiatric disorders. Despite its importance in the brain, relatively little is known about mechanisms that regulate synaptic dopamine release in vivo. And although the effects of dopamine on individual cells have been extensively studied, how dopamine signals are processed to change the dynamics of post synaptic neurons to execute changes of behavior is not well understood. The microscopic roundworm C. elegans offers the opportunity to study these aspects of dopamine signaling using powerful tools of molecular genetics and in vivo circuit analysis. Using behavioral genetics and newly developed methods for analysis of neural circuits in behaving animals we will (1) determine mechanisms that regulate dopamine release in response to appetitive stimuli and postsynaptic and (2) determine circuit mechanisms that transform dopamine signaling events into lasting changes in behavior. Because of the ancient and conserved functions of dopamine signaling in the animal nervous system, we propose that our studies will also advance understanding of pre- and postsynaptic mechanisms in dopamine systems of the human brain and accelerate discovery of new approaches to understanding and treating diseases linked to dysfunction of dopaminergic systems.

神经调节剂多巴胺对于许多大脑功能都很重要：多巴胺神经元的丧失会导致运动障碍，如帕金森病；多巴胺信号传导是滥用药物和奖励和成瘾的神经生物学不可或缺的一部分；多巴胺信号是治疗靶标尽管它在大脑中很重要，但人们对它的了解却相对较少。关于调节体内突触多巴胺释放的机制，尽管多巴胺对体内的影响。单个细胞已被广泛研究，如何处理多巴胺信号以改变动力学突触后神经元执行行为变化的机制尚不清楚。线虫提供了使用强大的工具研究多巴胺信号传导这些方面的机会使用行为遗传学和新开发的方法进行分子遗传学和体内回路分析。通过分析行为动物的神经回路，我们将 (1) 确定调节多巴胺的机制响应食欲刺激和突触后释放，并且（2）确定转变的电路机制由于多巴胺的古老且保守的功能，它可以将信号事件转变为持久的行为变化。动物神经系统中的多巴胺信号传导，我们建议我们的研究也将取得进展了解人脑多巴胺系统的突触前和突触后机制并加速发现理解和治疗与多巴胺能功能障碍相关疾病的新方法系统。