Dopamine Timing-Dependent Plasticity in Reward Learning
奖励学习中多巴胺时间依赖性可塑性
基本信息
- 批准号:9904760
- 负责人:
- 金额:$ 23.48万
- 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:2019-04-01 至 2023-02-28
- 项目状态:已结题
- 来源:
- 关键词:ADORA2A geneAction PotentialsAddressAgonistAreaBehaviorBrainCorpus striatum structureCoupledCuesCytosolDRD2 geneDataDependenceDistalDopamineDopamine D1 ReceptorDopamine D2 ReceptorDopamine ReceptorEtiologyEvoked PotentialsFiberFluorescenceGTP-Binding ProteinsGenerationsGlutamatesGoalsInositolLabelLearningLong-Term DepressionLong-Term PotentiationMediatingMemoryMental DepressionMetabotropic Glutamate ReceptorsMusNeuronsNucleus AccumbensPharmacologyPhasePlayPreventiveProtocols documentationReceptor ActivationRegulationReportingResearchRewardsRoleSchizophreniaSignal TransductionSiteSpecificityStructureSynapsesSynaptic plasticityTestingTherapeuticTrainingTransgenic MiceVentral Tegmental AreaWild Type Mouseaddictionbaseblindconditioningdesigndetectordopaminergic neuronexperimental studyinsightmesolimbic systemneurobiological mechanismneuropsychiatrynoveloptogeneticspostsynapticpressurepresynapticpreventpublic health relevancereceptorrelating to nervous systemresponseselective expressiontransmission processtripolyphosphate
项目摘要
Project Summary/Abstract
The mesolimbic dopamine (DA) system originating in the ventral tegmental area (VTA) plays a critical role in
reward-based learning. DA neurons in the VTA display phasic burst firing in response to unexpected primary
rewards. The timing of this bursting activity shifts to the onset of reward-predicting cues during repeated cue-
reward pairing, where cue presentation needs to precede reward delivery for effective conditioning. DA neuron
bursting gives rise to phasic DA transients lasting several seconds in the nucleus accumbens (NAc), a key site
for the formation of cue-reward memory. In general, reward-evoked DA transients are thought to promote
Hebbian plasticity induced by coordinated pairing of presynaptic and postsynaptic activities (pre-post pairing)
during conditioning. However, this assumption leads to the following conundrum (known as the distal reward
problem): how can DA, which communicates via slow intracellular signaling cascades, influence the
consequence of preceding neural activities to regulate synaptic plasticity? In addressing this question, it is of
note that DA neuron bursting to the cue develops during the early phase of cue-reward conditioning. This
raises the possibility that DA transients elicited by the cue, not by the reward, may act to drive the learning of
specific cue-reward associations as conditioning progresses. Thus, this project will explore the cellular
mechanisms supporting the idea that DA transients need to precede the pre-post pairing to regulate Hebbian
plasticity in the NAc. Cytosolic Ca2+ signaling dependent on the intracellular messenger inositol 1,4,5-
triphosphate (IP3) can act as a coincidence detector to mediate synaptic plasticity. Medium spiny projection
neurons (MSNs) in the NAc comprise two subpopulations, i.e., D1 receptor-positive and D2 receptor-positive
MSNs, that play opposing roles in reward-driven behavior. Our recent study has reported differential regulation
of IP3-Ca2+ signaling by preceding DA transients in these two MSN subpopulations. We hypothesize that DA
will enhance long-term potentiation (LTP) of glutamatergic transmission in D1-positive MSNs while preventing
LTP, or promoting long-term depression (LTD), in D2-positive MSNs through opposing regulation of IP3-Ca2+
signaling. Temporal rules governing DA action on plasticity will be examined by varying the timing of DA
transients, produced by local pressure ejection of DA or optogenetic stimulation of DA fibers, relative to the
pre-post pairing. The goal of this R21 project is to open a new line of research addressing the role and timing
of phasic DA signals in regulating synaptic plasticity underlying reward learning.
项目总结/摘要
起源于腹侧被盖区(VTA)的中脑边缘多巴胺(DA)系统在脑内多巴胺代谢中起着关键作用。
基于奖励的学习。腹侧被盖区的多巴胺能神经元对意外的初级放电反应时表现出阶段性爆发放电。
奖励这种突发活动的时间转移到奖励预测线索的开始,在重复的线索,
奖励配对,其中提示呈现需要先于奖励传递以实现有效条件反射。DA神经元
爆发引起持续数秒的多巴胺时相性瞬变,在脑桥核(NAc),一个关键部位
线索奖励记忆的形成。一般来说,奖励诱发的DA瞬变被认为是促进
由突触前和突触后活动的协调配对(前-后配对)诱导的赫布可塑性
在调理期间。然而,这一假设导致了以下难题(称为远端奖励
问题):通过缓慢的细胞内信号级联传递的DA如何影响
是先前神经活动调节突触可塑性的结果吗?在回答这个问题时,
注意,DA神经元对线索的爆发是在线索奖励条件反射的早期阶段发展起来的。这
提示引起的DA瞬变,而不是奖励,可能会驱动学习的可能性。
具体的线索奖励协会作为条件反射的进展。因此,该项目将探索细胞
机制支持的想法,DA瞬变需要之前的前后配对,以调节赫布
在NAc的可塑性。胞浆Ca 2+信号依赖于胞内信使肌醇1,4,5-
三磷酸(IP 3)可以作为一个重合检测器来介导突触可塑性。中棘突
NAc中的神经元(MSN)包括两个亚群,即,D1受体阳性和D2受体阳性
MSN,在奖励驱动的行为中扮演相反的角色。我们最近的研究报告了差异调节
在这两个MSN亚群中,IP 3-Ca 2+信号通过之前的DA瞬变而被抑制。我们假设检察官
将增强D1阳性MSN中突触能传递的长时程增强(LTP),同时防止
LTP,或通过IP 3-Ca 2+的反向调节促进D2阳性MSN中的长期抑郁(LTD)
发信号。通过改变DA作用的时间来研究DA对可塑性作用的时间规律
瞬态,由DA的局部压力喷射或DA纤维的光遗传学刺激产生,相对于
前后配对。这个R21项目的目标是开辟一条新的研究路线,解决
的相位DA信号在调节突触可塑性潜在的奖励学习。
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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HITOSHI MORIKAWA其他文献
HITOSHI MORIKAWA的其他文献
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{{ truncateString('HITOSHI MORIKAWA', 18)}}的其他基金
Experience-Dependent Regulation of Reward Learning and Addiction Vulnerability
奖励学习和成瘾脆弱性的经验依赖性调节
- 批准号:
10579290 - 财政年份:2022
- 资助金额:
$ 23.48万 - 项目类别:
Experience-Dependent Regulation of Reward Learning and Addiction Vulnerability
奖励学习和成瘾脆弱性的经验依赖性调节
- 批准号:
10442868 - 财政年份:2022
- 资助金额:
$ 23.48万 - 项目类别:
Alcohol Action on Neurons in the Brain Reward Circuit
酒精对大脑奖赏回路中神经元的作用
- 批准号:
7943743 - 财政年份:2007
- 资助金额:
$ 23.48万 - 项目类别:
Alcohol Action on Neurons in the Brain Reward Circuit
酒精对大脑奖赏回路中神经元的作用
- 批准号:
7857913 - 财政年份:2007
- 资助金额:
$ 23.48万 - 项目类别:
Alcohol Action on Neurons in the Brain Reward Circuit
酒精对大脑奖赏回路中神经元的作用
- 批准号:
8080489 - 财政年份:2007
- 资助金额:
$ 23.48万 - 项目类别:
Alcohol Action on Neurons in the Brain Reward Circuit
酒精对大脑奖赏回路中神经元的作用
- 批准号:
7631373 - 财政年份:2007
- 资助金额:
$ 23.48万 - 项目类别:
Alcohol Action on Neurons in the Brain Reward Circuit
酒精对大脑奖赏回路中神经元的作用
- 批准号:
7253689 - 财政年份:2007
- 资助金额:
$ 23.48万 - 项目类别:
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