Plasticity and Function of Dopamine Circuits Regulating the Transition to Habit
多巴胺回路的可塑性和功能调节习惯的转变
基本信息
- 批准号:10743544
- 负责人:
- 金额:$ 50.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-16 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAnatomyAreaAutomationBehaviorBehavioralBrainBrain regionCellsComplexCorpus striatum structureDataDendritesDependenceDiseaseDisinhibitionDistalDopamineElectrophysiology (science)Environmental Risk FactorExcitatory SynapseFiberFormulationFoundationsFunctional disorderFutureGeneticGoalsHabitsIndividualInfluentialsLaboratoriesLearningLightingLiquid substanceLocationLong-Term PotentiationMapsMeasuresMental disordersMidbrain structureModelingMonkeysMotor SkillsMusNeurobiologyNeuronsNeurosciencesObsessive-Compulsive DisorderOutcomePacemakersPatternPhotometryPositioning AttributeProcessPropertyRegulationResearchResearch PersonnelResponse to stimulus physiologyRestRewardsRoleSliceSolidSourceSubstantia nigra structureSymptomsSynapsesSynaptic plasticityTechnical ExpertiseTechnologyTestingTimeTrainingWorkaddictionadverse outcomebehavioral responsebehavioral studycandidate identificationcell typecompulsioncostdopaminergic neuronexperimental studyfield studyflexibilityin vivoinnovationmaladaptive behaviormotivated behaviorneural circuitneuromechanismneuropsychiatric disorderoptogeneticsrecruitrepetitive behaviorskill acquisitionskills trainingtheories
项目摘要
PROJECT SUMMARY/ABSTRACT
Habits and motor skills are essential to survival, allowing for the fast, fluid, and automatic execution of actions
that have repeatedly proved beneficial. Despite their utility, habits and motor skills come at a cost: a loss of
behavioral flexibility. Automated actions that were previously beneficial can become maladaptive if action-
outcome contingencies shift. Because automated actions are hard to adjust once established, maladaptive
behaviors can persist, as is hypothesized to occur in obsessive-compulsive disorder (OCD) and addiction, for
example. A major long-term goal of my laboratory is to understand how and why actions become automated
through the closely related processes of habit formation and motor skill acquisition. What is the normal process
of automation and how may it go awry in psychiatric disorders? Previous studies have identified a key role for
the dorsolateral striatum (DLS), but it remains unclear how the DLS becomes engaged in behavior over time as
goal-directed actions are repeated and automated. Existing theories have been difficult to test empirically, stalling
the field. This project takes advantage of recent technological advancements in neural circuit tracing,
intersectional genetic targeting of cell types, and optogenetics and fiber photometry, innovatively combined, to
bring new data to bear on the problem and to inspire work on fresh hypotheses. Our main objective in this
proposal is to characterize the neural circuits controlling dopaminergic input to the DLS, which is critical for
regulating synaptic plasticity in this brain region. We will identify synaptic plasticity mechanisms in the
dopaminergic midbrain that underlie changes in DLS dopamine release related to habit formation and motor skill
acquisition, and empirically test a long-standing hypothesis in the field, the Ascending Spiral Hypothesis, which
posits that activity in goal-directed regions of the striatum disinhibits DLS dopamine release. We will reformulate
the Ascending Spiral Hypothesis as needed based on new data. Our innovative approach integrates circuit
tracing, electrophysiology, optogenetics, fiber photometry, and behavioral studies across three specific aims,
spanning levels of analysis from detailed subcellular synaptic input mapping to in vivo circuit function. With the
successful completion of this project, we will provide a robust characterization of the Ascending Spiral circuit and
its role in controlling DLS dopamine dynamics before, during, and after action automation. This research will
have a broad impact as it will answer fundamental questions about the neural mechanisms underlying action
automation. By understanding the brain circuit activity allowing transitions from goal-directed control to habits
and motor skills, we will unlock a new point of entry into studying how complex polygenic diseases such as OCD
and addiction emerge from the confluence of genetic and environmental factors on circuit function.
项目摘要/摘要
习惯和运动技能是生存所必需的,能够快速、流畅和自动地执行动作
这已多次被证明是有益的。尽管它们有用,但习惯和运动技能是有代价的:失去
行为灵活性。以前有益的自动操作可能会变得不适应,如果操作-
结果意外情况发生了变化。因为自动操作一旦建立就很难调整,适应性差
行为可以持续存在,假设发生在强迫症(OCD)和成瘾中,
举个例子。我的实验室的一个主要长期目标是了解如何以及为什么操作变得自动化
通过习惯形成和运动技能获得这两个密切相关的过程。正常的流程是什么?
自动化,以及它在精神障碍方面可能会出现什么问题?以前的研究已经确定了一个关键的作用
背外侧纹状体(DLS),但尚不清楚DLS是如何随着时间的推移而参与行为的
以目标为导向的行动是重复和自动化的。现有的理论很难进行实证检验,停滞不前
田野。该项目利用了神经回路追踪方面的最新技术进步,
细胞类型的交叉遗传靶向,以及光遗传学和纤维光度学,创新性地结合在一起,以
将新的数据应用到这个问题上,并启发对新假设的研究。我们在这方面的主要目标
建议是表征控制多巴胺能输入到DLS的神经电路,这对
调节这个脑区的突触可塑性。我们将确定突触可塑性机制在
多巴胺能中脑多巴胺释放的变化与习惯形成和运动技能有关
获取,并对该领域中的一个长期存在的假说--上升螺旋假说进行实证检验,该假说
假设纹状体目标定向区域的活动抑制了DLS多巴胺的释放。我们将重新制定
基于新数据的上升螺旋假说。我们的创新方法集成了电路
追踪,电生理学,光遗传学,纤维光度学,和三个特定目标的行为研究,
从详细的亚细胞突触输入映射到体内电路功能的跨层次分析。与
这个项目的成功完成,我们将提供上升螺旋电路和
它在控制动作自动化前、中和后的DLS多巴胺动态中的作用。这项研究将
有广泛的影响,因为它将回答有关潜在行动的神经机制的基本问题
自动化。通过了解大脑回路活动,实现从目标导向控制到习惯的转变
和运动技能,我们将打开一个新的切入点,研究复杂的多基因疾病,如强迫症
而成瘾的出现是遗传和环境因素对电路功能的影响。
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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Talia Newcombe Lerner其他文献
Talia Newcombe Lerner的其他文献
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{{ truncateString('Talia Newcombe Lerner', 18)}}的其他基金
Contributions of Parallel Nigrostriatal Dopamine Circuits to Reward Learning and Habit Formation
平行黑质纹状体多巴胺回路对奖励学习和习惯形成的贡献
- 批准号:
9086170 - 财政年份:2016
- 资助金额:
$ 50.27万 - 项目类别:
The Role of Striatonigrostriatal Circuitry in Habit Formation
纹状体黑质纹状体回路在习惯形成中的作用
- 批准号:
8780490 - 财政年份:2014
- 资助金额:
$ 50.27万 - 项目类别:
The Role of Striatonigrostriatal Circuitry in Habit Formation
纹状体黑质纹状体回路在习惯形成中的作用
- 批准号:
8926702 - 财政年份:2014
- 资助金额:
$ 50.27万 - 项目类别:
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