Zona Incerta Contributions to Reward and Cocaine Addiction
不确定区对奖励和可卡因成瘾的贡献
基本信息
- 批准号:9816466
- 负责人:
- 金额:$ 34.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-15 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:Action PotentialsAddictive BehaviorAffectAnatomyAnimalsAxonBehaviorBehavior DisordersBehavioralBinge EatingBrainBrain regionCellsCocaineCocaine DependenceDeep Brain StimulationDiseaseDopamineEating BehaviorElectrophysiology (science)FOS geneFatty acid glycerol estersFeeding behaviorsFoodGlutamatesGoalsGoldHumanImpulsivityKnowledgeLeadMapsModernizationMotivationMusNatureNeuronsNucleus AccumbensOutputParkinson DiseasePathological GamblingPathway interactionsPatientsPeriodicityPharmaceutical PreparationsPhysiologicalPhysiologyPilot ProjectsPlayPopulationPrefrontal CortexPresynaptic TerminalsPsychological reinforcementRabiesRewardsRoleScanningSelf AdministrationSiteStructureStructure of subthalamic nucleusSubthalamic structureSynapsesSynaptic PotentialsSynaptic TransmissionTechniquesTestingThalamic structureTimeTracerTremorUncertaintyVentral Tegmental AreaWorkaddictionbasecell typedopaminergic neurondrug seeking behaviorexperimental studygamma-Aminobutyric Acidimprovedin vivoinsightmotivated behaviormotor disordernoveloptogeneticspatient subsetspreferencerelating to nervous systemscreeningside effecttoolvirus geneticszona incerta
项目摘要
The zona incerta (ZI), or “zone of uncertainty”, is a poorly-characterized structure in the subthalamus.
The caudal ZI and the adjacent subthalamic nucleus (STN) have been implicated in impulsive and motivational
disorders in a subset of patients with Parkinson's disease (PD), and recent work has shown that optogenetic
activation of the ZI robustly induces binge-like eating behavior in mice. Thus, both human and animal studies
point to an unappreciated role for the ZI in regulating motivational and behavioral disorders. However, the
underlying mechanisms remain largely unexplored. Recently, rabies-based, whole-brain monosynaptic
retrograde mapping has revealed that the ZI sends projections to the ventral tegmental area (VTA). VTA
dopamine and GABA neurons play a critical role in reward, motivation and addiction. We propose to test the
hypothesis that the ZI regulates motivated and addictive behavior via its direct projection to the VTA. In this
proposal, we will apply a variety of cutting-edge tools including viral-genetic anatomic and optogenetic circuit-
mapping, optogenetic and chemogenetic stimulation and inhibition, electrophysiology, and other techniques to
comprehensively study the underlying connectivity and physiology of the ZI-VTA pathway. Overall, our
objectives include the following: characterize the cell type-specific connectivity between the ZI and the VTA
using modern anatomic tools and electrophysiology (Aim I); determine how these connections affect neuronal
activity in the major cell types of the VTA, and dopamine release in the nucleus accumbens, in vivo (Aim II);
and determine how optogenetic and chemogenetic modulation of these pathways can drive or disrupt natural
reward and cocaine reward-related behaviors (Aim III). These comprehensive studies will provide mechanistic
insight into a structure and pathway of which very little is known. Completion of the proposed studies will not
only identify novel neural substrates of reward and motivation, but will fill a knowledge gap that may ultimately
lead to improved treatments for motivational and addictive disorders.
不确定带(Zi),或“不确定区”,是丘脑下部的一个特征不佳的结构。
ZI尾侧核和邻近的丘脑底核(STN)与冲动和动机有关
帕金森氏病(PD)患者中的一组疾病,最近的研究表明光遗传学
子的激活强烈地诱导了小鼠的暴饮式进食行为。因此,无论是人类研究还是动物研究
指出子在调节动机和行为障碍方面的作用没有得到重视。然而,
潜在的机制在很大程度上仍未得到探索。最近,基于狂犬病的全脑单突触
逆行标测显示,ZI向腹侧被盖区(VTA)发送投射。VTA
多巴胺和GABA神经元在奖赏、动机和成瘾中起着关键作用。我们建议测试一下
假设ZI通过其向VTA的直接投射来调节动机和成瘾行为。在这
建议,我们将应用各种尖端工具,包括病毒遗传解剖和光遗传电路-
测绘、光发生和化学发生刺激和抑制、电生理学和其他技术
全面研究Zi-VTA通路的潜在连通性和生理学。总的来说,我们的
目标包括:描述ZI和VTA之间特定细胞类型的连通性
使用现代解剖学工具和电生理学(目标I);确定这些连接如何影响神经元
体内VTA主要细胞类型的活性和伏隔核多巴胺的释放(目标II);
并确定这些途径的光遗传和化学发生调制如何驱动或破坏自然
奖赏和可卡因奖赏相关行为(目标三)。这些综合研究将提供机械性的
洞察一种鲜为人知的结构和途径。建议的研究将不会完成
只识别奖励和激励的新神经基础,但将填补一个知识空白,这最终可能
导致改善对激励性和成瘾障碍的治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Qing-song Liu', 18)}}的其他基金
Zona Incerta Contributions to Reward and Cocaine Addiction
不确定区对奖励和可卡因成瘾的贡献
- 批准号:
10439447 - 财政年份:2019
- 资助金额:
$ 34.65万 - 项目类别:
Zona Incerta Contributions to Reward and Cocaine Addiction
不确定区对奖励和可卡因成瘾的贡献
- 批准号:
10651652 - 财政年份:2019
- 资助金额:
$ 34.65万 - 项目类别:
Zona Incerta Contributions to Reward and Cocaine Addiction
不确定区对奖励和可卡因成瘾的贡献
- 批准号:
10190877 - 财政年份:2019
- 资助金额:
$ 34.65万 - 项目类别:
Mechanistic studies of cAMP effectors in cocaine addiction
cAMP效应子在可卡因成瘾中的机制研究
- 批准号:
10155454 - 财政年份:2014
- 资助金额:
$ 34.65万 - 项目类别:
Regulation of dopamine neuronal activity and depressive behavior by HCN channels
HCN 通道对多巴胺神经元活动和抑郁行为的调节
- 批准号:
8925142 - 财政年份:2014
- 资助金额:
$ 34.65万 - 项目类别:
Mechanistic studies of phosphodiesterase inhibitors in cocaine addiction
磷酸二酯酶抑制剂治疗可卡因成瘾的机制研究
- 批准号:
8694584 - 财政年份:2014
- 资助金额:
$ 34.65万 - 项目类别:
Mechanistic studies of cAMP effectors in cocaine addiction
cAMP效应子在可卡因成瘾中的机制研究
- 批准号:
10646409 - 财政年份:2014
- 资助金额:
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Mechanistic studies of cAMP effectors in cocaine addiction
cAMP效应子在可卡因成瘾中的机制研究
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9975107 - 财政年份:2014
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Mechanistic studies of cAMP effectors in cocaine addiction
cAMP效应子在可卡因成瘾中的机制研究
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9816458 - 财政年份:2014
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Mechanistic studies of phosphodiesterase inhibitors in cocaine addiction
磷酸二酯酶抑制剂治疗可卡因成瘾的机制研究
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9012061 - 财政年份:2014
- 资助金额:
$ 34.65万 - 项目类别:
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