Neuromodulation of Brain States

大脑状态的神经调节

基本信息

批准号：
10311052
负责人：
LIQUN LUO
金额：
$ 66.21万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10311052
关键词：
Address Anatomy Anxiety Architecture Axon Behavior Behavioral Behavioral Paradigm Biological Assay Brain Brain Diseases Brain Stem Brain region Cell Nucleus Cells Complex Data Disease Dopamine Dorsal Foundations Frequencies Future Genetic Glutamate Transporter Heterogeneity Human Hunger Hypothalamic structure Impulsivity Link Location Mammals Mediating Mental Depression Midbrain structure Modernization Moods Mus Neurons Neurotransmitters Norepinephrine Output Parkinson Disease Pattern Phenotype Physiological Physiology Population Prosencephalon Rabies Regulation SLC17A8 gene Schizophrenia Serotonergic System Serotonin Societies Synapses System Techniques Thirst Transgenic Mice Water base behavioral study dopaminergic neuron drinking excitatory neuron experimental study gamma-Aminobutyric Acid inhibitory neuron locus ceruleus structure monoamine motivated behavior neuroregulation optogenetics preoptic nucleus tool unpublished works virus genetics

项目摘要

PROJECT SUMMARY The monoamines, which include dopamine, norepinephrine, and serotonin, are evolutionarily conserved neurotransmitters that modulate the activity of excitatory and inhibitory neurons throughout the entire brain, and are thus essential for diverse aspects of physiology and behavior. Abnormalities of monoamine systems contribute to numerous brain disorders including schizophrenia, depression, and Parkinson's disease. We recently developed viral-genetic tools to determine the input, output, and input–output relationships of a given neuronal population at the scale of the entire mouse brain, and discovered contrasting input–output architectures between locus coeruleus norepinephrine neurons and midbrain dopamine neurons. Here, we apply these tools to study the organization and function of the dorsal raphe (DR) serotonin system, which provides major serotoninergic input to the forebrain to regulate diverse . functions and brain states including mood, impulsivity, anxiety, as well as hunger and thirst. Using rabies-mediated trans-synaptic tracing, we previously defined the input architecture to the entire populations of DR-serotonin and DR-GABA neurons However, our unpublished work revealed considerable heterogeneity within the DR serotonin system and suggests that it consists of parallel sub- systems that differ in input, output, and neurotransmitter phenotypes. We propose that each DR serotonin sub-system may carry out a specific subset of the diverse functions ascribed to the DR-serotonin neurons. We plan to complete our characterization of the anatomical organization of the DR serotonin sub- systems, addressing the questions of how axons of each sub-system divide up the projections of the entire DR serotonin system, and what is the input–output relationship for each DR serotonin sub-system. These will lay a foundation for all future studies of DR-serotonin neurons. We also propose to identify behavioral functions of a subset of these sub-systems by manipulating and recording serotonin neuron subtypes in anxiety- and depression-like states known to involve serotonin, as well as new behavioral paradigms. Finally, because previous studies and our own unpublished data suggest a strong link between serotonin and thirst, we will explore the circuit and cellular mechanisms by which serotonin regulates thirst-motivated behavior using quantitative and sensitive assays we have established based on a technique we developed to gain genetic access of thirst-activated neurons. The integration of anatomical, physiological, and behavioral studies on genetic-, projection-, and activity-defined neuronal populations proposed here will help dissect the complex serotonin system into specific sub-systems and advance our understanding of how serotonin modulates diverse physiological functions and behaviors.

项目摘要单胺，包括多巴胺，去甲肾上腺素和5-羟色胺，是进化保守的神经递质调节整个大脑的兴奋和抑制神经元的活性，因此，对于生理和行为的潜水员方面至关重要。单胺异常系统会导致许多脑部疾病，包括精神分裂症，抑郁症和帕金森氏症疾病。我们最近开发了病毒遗传工具来确定输入，输出和输入输出在整个小鼠大脑的规模上给定神经元种群的关系，并发现对比的输入 - 输出体系结构，位于肠系膜的基因座神经元与中脑之间多巴胺神经元。在这里，我们应用这些工具来研究背raphe的组织和功能（DR）5-羟色胺系统，该系统为前脑提供主要的5-羟色胺能量输入，以调节潜水员。功能和大脑状态，包括情绪，冲动，动画以及饥饿和第三。使用狂犬病介导的反式突触跟踪，我们先前将输入体系结构定义为整个但是，我们未发表的工作揭示了Dr-Serotonin和Dr-Gaba神经元的种群 5-羟色胺系统内相当多的异质性，并表明它由平行的子组成输入，输出和神经递质表型不同的系统。我们建议每个羟色胺博士子系统可以执行分配给DR-羟蛋白神经元的潜水功能的特定子集。我们计划完成对5-羟色胺亚基解剖组织的表征系统，解决每个子系统轴突如何将整个项目的项目划分的问题 5-羟色胺系统，以及每个5-羟色胺子系统的输入 - 输出关系是什么。这些将为所有未来对苏罗替肽神经元的研究奠定基础。我们还建议识别行为通过操纵和记录5-羟色胺神经元亚型的子集的子集的功能已知涉及5-羟色胺以及新行为范式的焦虑和抑郁状态。最后，由于以前的研究和我们自己未发表的数据表明了血清素之间的牢固联系第三，我们将探索5-羟色胺调节3-动机的电路和细胞机制使用定量和敏感测定的行为我们基于我们开发的技术建立获得第三活化神经元的遗传获取。解剖学，生理和有关此处提出的遗传，投影和活性定义的神经元种群的行为研究帮助将复杂的5-羟色胺系统剖析到特定的子系统中，并提高我们对 5-羟色胺如何调节潜水员的生理功能和行为。

项目成果

期刊论文数量（17）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Thirst-associated preoptic neurons encode an aversive motivational drive.

DOI：
10.1126/science.aan6747
发表时间：
2017-09-15
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
Allen WE;DeNardo LA;Chen MZ;Liu CD;Loh KM;Fenno LE;Ramakrishnan C;Deisseroth K;Luo L
通讯作者：
Luo L

Genetic Dissection of Neural Circuits: A Decade of Progress.

DOI：
10.1016/j.neuron.2018.03.040
发表时间：
2018-04-18
期刊：
Neuron
影响因子：
16.2
作者：
Luo L;Callaway EM;Svoboda K
通讯作者：
Svoboda K

The Temporal Association Cortex Plays a Key Role in Auditory-Driven Maternal Plasticity.

DOI：
10.1016/j.neuron.2020.05.004
发表时间：
2020-08-05
期刊：
Neuron
影响因子：
16.2
作者：
Tasaka GI;Feigin L;Maor I;Groysman M;DeNardo LA;Schiavo JK;Froemke RC;Luo L;Mizrahi A
通讯作者：
Mizrahi A

Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks.

DOI：
10.1016/j.cell.2020.11.046
发表时间：
2021-01-21
期刊：
Cell
影响因子：
64.5
作者：
Lui JH;Nguyen ND;Grutzner SM;Darmanis S;Peixoto D;Wagner MJ;Allen WE;Kebschull JM;Richman EB;Ren J;Newsome WT;Quake SR;Luo L
通讯作者：
Luo L

Brain Circuit of Claustrophobia-like Behavior in Mice Identified by Upstream Tracing of Sighing.