Mechanisms of Dopamine Action in Learning: Implications for Addiction
Mechanisms of Dopamine Action in Learning: Implications for Addiction
批准号:
10553236
负责人:
Patricia H. Janak
金额:
$47.16万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
未结题
起止时间:
2014-04-01 至 2025-01-31
关键词:
Addictive BehaviorAnesthesia proceduresAnimalsAssociation LearningBehaviorBehavior ControlBehavior DisordersBehavioralBrainConceptionsCorpus striatum structureCuesDevelopmentDiseaseDopamineDorsalElectrophysiology (science)ElementsEnvironmentEvolutionFOS geneGoalsHumanHyperphagiaIncentivesInfusion proceduresLearningLightLinkMeasuresMediatingMidbrain structureModelingMovementNeuronsNeurotransmittersNucleus AccumbensOperant ConditioningPathologicPerformancePharmaceutical PreparationsPharmacologyPlayPopulationProcessPsychological reinforcementPublishingRat TransgeneRattusRewardsRoleShapesStimulusSubstance Use DisorderSubstance abuse problemSubstantia nigra structureSystemTestingTimeTrainingVentral Tegmental AreaWorkaddictionapproach behaviorconditioningdopamine systemdopaminergic neurondrug relapsedrug rewarddrug seeking behaviorin vivolearned behaviormesolimbic systemnerve supplyneuralneural patterningneuromechanismneurotransmissionoptogeneticspars compactapsychologicrecruitresponsetransmission process
中文摘要
项目摘要
中脑边缘多巴胺,沿着其腹侧纹状体靶点,在
巴甫洛夫奖励学习。巴甫洛夫奖励学习过程的基础是许多方面
在药物复吸中起着关键作用。工具性学习
过程也形成了药物寻求行为的基本要素,并且可能取决于
对黑质纹状体背侧纹状体多巴胺神经支配的影响。在这里我们试图理解
纹状体靶点内中脑边缘和黑质纹状体多巴胺作用如何介导选择
奖励寻求行为的组成部分,并测试这些之间的相互作用
系统有助于正常和病态的寻求奖励的行为。我们专注于
多巴胺,因为自然和药物奖励都能激活多巴胺神经元,
在我们最近的发现中证实,多巴胺神经元激活,当取代
奖励,驱动特定形式的联想学习,涉及成瘾行为。
在这里,使用Th:Cre转基因大鼠限制通道视紫红质表达多巴胺,
神经元,我们利用选择性激活中脑边缘多巴胺的能力,
神经元,以更好地了解其对行为,神经活动和整合的影响,
腹侧和背侧纹状体系统。我们测试中脑边缘多巴胺神经元
奖励相关的激活在特定形式的兴奋过程中招募更多的背侧纹状体回路。
学习一个突出的假设假定,随着时间的推移,奖励寻求取决于更多的
背侧纹状体回路作为行为控制成为习惯。因此,我们还要求
激活中脑边缘多巴胺系统是否可以加速习惯性
对自然或药物的奖励作出反应。此外,我们将确定神经信号
介导由中脑边缘多巴胺激活调节的行为,以揭示
下游神经元群体的神经变化,介导的性能,
这些多巴胺介导的习得行为。这些研究将提供新的信息
关于腹侧和背侧纹状体回路的单独和交互作用,
寻求奖励的行为,可以由多巴胺启动,并与我们的
对涉及暴饮暴食和物质使用障碍的行为障碍的理解。
英文摘要
Project summary
Mesolimbic dopamine, along with its ventral striatal targets, plays a major role in
Pavlovian reward learning. Pavlovian reward learning processes underlie many aspects
of drug seeking behavior and play a critical role in drug relapse. Instrumental learning
processes also form a fundamental element of drug seeking behavior, and may depend
on nigrostriatal dopamine innervation of dorsal striatum. Here we seek to understand
how mesolimbic and nigrostriatal dopamine action within striatal targets mediates select
components of reward-seeking behavior, and to test whether interactions between these
systems contribute to normal and pathological reward-seeking behavior. We focus on
dopamine because both natural and drug rewards activate dopamine neurons, and, as
confirmed in our recent findings, dopamine neuron activation, when substituted for
reward, drives specific forms of associative learning implicated in addictive behavior.
Here, using the Th:Cre transgenic rat to limit channelrhodopsin expression to dopamine
neurons, we take advantage of the ability to selectively activate mesolimbic dopamine
neurons to better understand their impact on behavior, neural activity, and integration of
ventral and dorsal striatal systems. We test whether mesolimbic dopamine neuron
reward-related activation recruits more dorsal striatal circuits during specific forms of
learning. A prominent hypothesis posits that reward seeking depends over time on more
dorsal striatal circuits as behavioral control becomes habitual. Thus, we also ask
whether activating mesolimbic dopamine systems can hasten development of habitual
responding for natural or drug reward. In addition, we will determine neural signals
mediating behaviors conditioned by mesolimbic dopamine activation in order to reveal
neural changes in downstream neuronal populations that mediate the performance of
these dopamine-mediated learned behaviors. These studies will provide new information
on the separate and interactive contributions of ventral and dorsal striatal circuits to
reward seeking behavior that can be initiated by dopamine, and are relevant for our
understanding of behavioral disorders involving overeating and substance use disorders.
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From circuits to behaviour in the amygdala.
从杏仁核中的电路到行为。
DOI:
10.1038/nature14188
发表时间:
2015-01-15
期刊:
Nature
影响因子:
64.8
作者:
[Janak PH, Tye KM]
通讯作者:
Tye KM
Dorsomedial Striatal Activity Tracks Completion of Behavioral Sequences in Rats.
背内侧纹状体活动跟踪大鼠行为序列的完成。
DOI:
10.1523/eneuro.0279-21.2021
发表时间:
2021
期刊:
eNeuro
影响因子:
3.4
作者:
[Vandaele,Youna, Ottenheimer,DavidJ, Janak,PatriciaH]
通讯作者:
Janak,PatriciaH
DOI:
10.1101/lm.053472.121
发表时间:
2021-12
期刊:
Learning & memory (Cold Spring Harbor, N.Y.)
影响因子:
--
作者:
[Garr E, Padovan-Hernandez Y, Janak PH, Delamater AR]
通讯作者:
Delamater AR
Basolateral amygdala and orbitofrontal cortex, but not dorsal hippocampus, are necessary for the control of reward-seeking by occasion setters.
基底外侧杏仁核和眶额皮质,但不是背侧海马,对于控制场合设定者寻求奖励是必需的。
DOI:
10.1007/s00213-022-06227-0
发表时间:
2023
期刊:
Psychopharmacology
影响因子:
3.4
作者:
[Fraser,KurtM, Janak,PatriciaH]
通讯作者:
Janak,PatriciaH
DOI:
10.1038/s41593-018-0191-4
发表时间:
2018-08
期刊:
Nature neuroscience
影响因子:
25
作者:
[Saunders BT, Richard JM, Margolis EB, Janak PH]
通讯作者:
Janak PH
共 13 条
Amygdala neural circuits in alcohol intake
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批准号:10518250
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项目类别:
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资助金额:$6.44万
-
财政年份:2019
-
负责人:Patricia H. Janak
-
依托单位:
Amygdala neural circuits in alcohol intake
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批准号:10362742
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项目类别:
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资助金额:$39.49万
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财政年份:2019
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负责人:Patricia H. Janak
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依托单位:
Amygdala neural circuits in alcohol intake
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批准号:10795152
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项目类别:
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资助金额:$6.44万
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财政年份:2019
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负责人:Patricia H. Janak
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依托单位:
Amygdala neural circuits in alcohol intake
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批准号:10581530
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项目类别:
-
资助金额:$39.49万
-
财政年份:2019
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负责人:Patricia H. Janak
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依托单位:
Amygdala and Striatal Neural Circuits Controlling Alcohol Intake
-
批准号:10401866
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项目类别:
-
资助金额:$36.84万
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财政年份:2018
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负责人:Patricia H. Janak
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依托单位:
Amygdala and Striatal Neural Circuits Controlling Alcohol Intake
-
批准号:9922827
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项目类别:
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资助金额:$36.84万
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财政年份:2018
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负责人:Patricia H. Janak
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依托单位:
Optogenetic Testing of Mechanims of Dopamine Action in Pavlovian Learning
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批准号:9041564
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项目类别:
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资助金额:$36.09万
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财政年份:2015
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负责人:Patricia H. Janak
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依托单位:
Optogenetic Testing of Mechanims of Dopamine Action in Pavlovian Learning
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批准号:9031892
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项目类别:
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资助金额:$35.9万
-
财政年份:2015
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负责人:Patricia H. Janak
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依托单位:
Mechanisms of Dopamine Action in Learning: Implications for Addiction
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批准号:10089221
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项目类别:
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资助金额:$47.16万
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财政年份:2014
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负责人:Patricia H. Janak
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依托单位:
Mechanisms of Dopamine Action in Learning: Implications for Addiction
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批准号:9897470
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项目类别:
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资助金额:$47.16万
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财政年份:2014
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负责人:Patricia H. Janak
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依托单位:
Mechanisms of Dopamine Action in Learning: Implications for Addiction
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批准号:10356018
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资助金额:$47.16万
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财政年份:2014
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负责人:Patricia H. Janak
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依托单位:
Optogenetic Testing of Mechanims of Dopamine Action in Pavlovian Learning
-
批准号:8719668
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项目类别:
-
资助金额:$35.49万
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财政年份:2014
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负责人:Patricia H. Janak
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依托单位:
Pilot Project
-
批准号:8794385
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项目类别:
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资助金额:$3.39万
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财政年份:2014
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负责人:Patricia H. Janak
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依托单位:
Striatal Mechanisms of Ethanol Seeking
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批准号:8669636
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项目类别:
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资助金额:$10.04万
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财政年份:2013
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负责人:Patricia H. Janak
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依托单位:
Context and Relapse to Ethanol-Seeking
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批准号:8675123
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项目类别:
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资助金额:$33.33万
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财政年份:2013
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负责人:Patricia H. Janak
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依托单位:
Striatal Mechanisms of Ethanol Seeking
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批准号:7692958
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项目类别:
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资助金额:$34.77万
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财政年份:2008
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负责人:Patricia H. Janak
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依托单位:
Neurochemical Bases for the Rewarding Effects of Ethanol
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批准号:8079065
-
项目类别:
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资助金额:$35.91万
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财政年份:2008
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负责人:Patricia H. Janak
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依托单位:
Striatal Mechanisms of Ethanol Seeking
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批准号:8128384
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项目类别:
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资助金额:$33.73万
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财政年份:2008
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负责人:Patricia H. Janak
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依托单位:
Neurochemical Bases for the Rewarding Effects of Ethanol
-
批准号:8278024
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项目类别:
-
资助金额:$35.91万
-
财政年份:2008
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负责人:Patricia H. Janak
-
依托单位:
Striatal Mechanisms of Ethanol Seeking
-
批准号:7919251
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项目类别:
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资助金额:$35.09万
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财政年份:2008
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负责人:Patricia H. Janak
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依托单位: