Dissecting the Synaptic and Cellular Actions of Dopamine in Vivo
剖析体内多巴胺的突触和细胞作用
基本信息
- 批准号:10504155
- 负责人:
- 金额:$ 69.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-08 至 2027-04-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectArousalAversive StimulusBehaviorBehavior TherapyBehavioralBrainCalciumCellsCharacteristicsChronicClosure by clampCorpus striatum structureCuesDataDetectionDopamineDopamine ReceptorElectrophysiology (science)Excitatory Postsynaptic PotentialsExcitatory SynapseFunctional disorderFutureGoalsImageImpairmentIn VitroKnowledgeLightLinkMammalsMeasuresMembraneMembrane PotentialsMental DepressionMental disordersMethodsMidbrain structureMolecular TargetMonitorMood DisordersMotivationMovementMusNeurologicNeuromodulatorNeuronsObsessive-Compulsive DisorderOutputParkinson DiseasePathway interactionsPharmacologyPhasePhysiologicalPopulationPopulation DynamicsPropertyPsychotic DisordersPublishingReportingRewardsRoleSensorySignal TransductionStimulusSynapsesSynaptic plasticityTechniquesTestingTimeTranslatingWorkaddictionawakecell typedopaminergic neuronexperimental studyextracellularin vivoin vivo calcium imaginginsightmotivated behaviornervous system disorderneuropsychiatric disorderneuroregulationnovelnovel therapeutic interventionoptogeneticsphase changerelating to nervous systemresponsetwo photon microscopy
项目摘要
Project Summary
The neuromodulator dopamine is critical for motivating, performing, and reinforcing goal-directed behaviors, and
deficits in dopamine signaling are common in neuropsychiatric disorders like depression, obsessive-compulsive
disorder, addiction and Parkinson’s disease. Central to our understanding of dopamine function is the notion
that phasic increases and decreases in extracellular dopamine levels in the striatum modulate striatal output to
modify behavior on short and long timescales. For instance, phasic elevations in striatal dopamine elicited by
salient stimuli and reward-predicting cues have been proposed to promote arousal, facilitate action initiation and
increase motivation to work on timescales of seconds to minutes, but also to modify future actions and behavioral
decisions on longer timescales extending to days. This raises a fundamental question: How does dopamine
modulate the activity of striatal neurons to exert its influence on behavior? Experiments in vitro have
revealed a myriad of molecular targets sensitive to modulation by dopamine. However, the net effects of these
changes on striatal output in vivo remain unknown. One reason is that few methods are capable of dissecting
dopamine’s cell type-specific neuromodulatory effects on synaptic strength, somatic excitability and network
dynamics in the awake, behaving brain. This proposal aims to fill this gap in knowledge using in vivo whole-cell
electrophysiology and two-photon microscopy, focusing initially on the neuromodulatory effects occurring on
timescales of seconds to minutes. Informed by our published and preliminary data with these techniques, we
will test the hypothesis that phasic dopamine transients reflecting positive and negative reward
prediction errors promote the activation of striatal projection neurons expressing D1- and D2-type
dopamine receptors (D1-SPNs and D2-SPNs), respectively, via a combination of intrinsic and synaptic
short-term plasticity mechanisms. To do so, we will harness our ability to record sub-threshold membrane
potential dynamics in vivo to reveal how behaviorally- and optogenetically-evoked dopamine transients alter the
intrinsic excitability of D1- and D2-SPNs (Aim 1) and the potency of excitatory synapses impinging on them (Aim
2). In Aim 3, we will employ calcium imaging to uncover the short-term influence of phasic dopamine transients
on striatal output. Together, our experiments will provide crucial mechanistic insights into the modulatory actions
of dopamine in vivo, shedding light on a key link between dopamine release and behavioral modifications, and
paving the way for novel therapeutic interventions aimed at treating neuropsychiatric disorders.
项目总结
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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Tanya Sippy其他文献
Tanya Sippy的其他文献
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{{ truncateString('Tanya Sippy', 18)}}的其他基金
Sensory Plasticity in the Auditory Striatum as an Impetus for Action Control
听觉纹状体的感觉可塑性作为行动控制的动力
- 批准号:
10576948 - 财政年份:2022
- 资助金额:
$ 69.34万 - 项目类别:
Dissecting the Synaptic and Cellular Actions of Dopamine in Vivo
剖析体内多巴胺的突触和细胞作用
- 批准号:
10662517 - 财政年份:2022
- 资助金额:
$ 69.34万 - 项目类别:
Function of Neocortical GABAergic Interneurons in Local Circuit Activations
新皮质 GABA 能中间神经元在局部回路激活中的功能
- 批准号:
8132306 - 财政年份:2008
- 资助金额:
$ 69.34万 - 项目类别:
Function of Neocortical GABAergic Interneurons in Local Circuit Activations
新皮质 GABA 能中间神经元在局部回路激活中的功能
- 批准号:
7541499 - 财政年份:2008
- 资助金额:
$ 69.34万 - 项目类别:
Function of Neocortical GABAergic Interneurons in Local Circuit Activations
新皮质 GABA 能中间神经元在局部回路激活中的功能
- 批准号:
7772330 - 财政年份:2008
- 资助金额:
$ 69.34万 - 项目类别:
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