High Content Functional Neuroanatomy of Endogenous GPCRs
内源性 GPCR 的高内涵功能神经解剖学
基本信息
- 批准号:10588941
- 负责人:
- 金额:$ 23.4万
- 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:2023-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAgonistAnatomyAnimal BehaviorAntibodiesAutoradiographyBehaviorBindingBiochemicalBiological AssayBiosensorBiotinBrainBrain DiseasesChronicChronic stressColorComplexDataDevelopmentDrug usageEquipmentExhibitsFc ReceptorFluorescenceG Protein-Coupled Receptor SignalingG-Protein-Coupled ReceptorsGTP-Binding ProteinsGeneticGoalsHeatingImageImmunohistochemistryIn SituInterventionLigandsLigationLinkLocationMeasurementMeasuresMediatingMetabotropic Glutamate ReceptorsMethodsModelingModificationMolecularMotivationMusNational Institute of Drug AbuseNeuroanatomyNeurosciencesNucleotidesOpioid ReceptorPainPatternPharmaceutical PreparationsPharmacological TreatmentPlayPropertyPublishingRattusReagentResolutionRewardsRoleSensorySignal TransductionSpecificityStressSubstance Use DisorderSynaptic TransmissionSystemTestingTherapeuticTissue FixationTissuesWithdrawaladdictionanatomic imagingbiological adaptation to stresscannabinoid receptorcell typechronic paincryostatdrug of abusedrug seeking behaviorexperimental studyfluorescence microscopeimaging modalityinnovationinsightinterestlaboratory equipmentmu opioid receptorsnegative affectneural circuitneuronal excitabilityneurotransmitter releasenonhuman primatenovelnovel therapeuticsopioid use disorderoptogeneticspharmacologicprotein activationratiometricreceptorreceptor couplingreceptor functionresponsesuccesstemporal measurementtoolvirtual
项目摘要
Abstract
G protein coupled receptors (GPCRs) modulate neuronal excitability and neurotransmitter release, and exert
profound effects on neural circuit functions. They play important roles in regulating motivation, reward, pain,
negative affect, and stress responses, which are all important in the context of substance use disorders
(SUDs). Exogenous ligands for several GPCRs have been shown to modify drug seeking behavior, which has
generated interest in GPCRs as targets for the development of pharmacological therapeutics for substance
use disorders. There are over 300 different non-sensory GPCRs expressed in mammalian brains, and
fundamental questions remain unanswered for all of them. For example, how does a given receptor's ability to
activate different G protein subtypes (Gi/o, Gs, Gq, G12/13) vary across neuroanatomical regions, cell types,
and subcellular regions? How are these properties altered in response to chronic drug use, chronic stress, or
chronic pain? To help answer these questions, we will develop new imaging methods in tissue sections for
neuroanatomical measurement of GPCR-mediated G protein activation, with subcellular resolution and G
protein subtype specificity. Our methods will only require common neuroscience equipment (cryostats and
fluorescence microscopes) and commercially available reagents. They will generate high-content information
on many GPCRs in healthy and diseased brains, and accelerate efforts to target GPCRs in addiction.
摘要
G蛋白偶联受体(GPCR)调节神经元兴奋性和神经递质释放,并发挥作用。
对神经回路功能的深远影响。它们在调节动机、奖励、疼痛、
负面影响和压力反应,这些在物质使用障碍的背景下都很重要
(SUD)。已经显示几种GPCR的外源性配体可以改变药物寻求行为,
产生了对GPCR作为开发药物治疗剂的目标的兴趣,
使用障碍。哺乳动物大脑中有超过300种不同的非感觉GPCR,
对所有这些人来说,根本问题仍然没有答案。例如,一个给定的受体的能力如何
激活不同的G蛋白亚型(Gi/o,Gs,Gq,G12/13)在神经解剖区域,细胞类型,
和亚细胞区域这些特性是如何在慢性药物使用、慢性压力或
慢性疼痛?为了帮助回答这些问题,我们将开发新的组织切片成像方法,
GPCR介导的G蛋白激活的神经解剖学测量,具有亚细胞分辨率和G
蛋白亚型特异性我们的方法只需要普通的神经科学设备(低温恒温器和
荧光显微镜)和市售试剂。他们将产生高内容的信息
在健康和患病大脑中的许多GPCR上,并加速针对成瘾中的GPCR的努力。
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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Patrick Ross O'Neill其他文献
Patrick Ross O'Neill的其他文献
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{{ truncateString('Patrick Ross O'Neill', 18)}}的其他基金
Nociceptin receptor signaling and regulation of dopamine transmission in drug reward circuitry
伤害感受肽受体信号传导和药物奖赏回路中多巴胺传递的调节
- 批准号:
10004764 - 财政年份:2017
- 资助金额:
$ 23.4万 - 项目类别:
Nociceptin receptor signaling and regulation of dopamine transmission in drug reward circuitry
伤害感受肽受体信号传导和药物奖赏回路中多巴胺传递的调节
- 批准号:
9164285 - 财政年份:2017
- 资助金额:
$ 23.4万 - 项目类别:
Nociceptin receptor signaling and regulation of dopamine transmission in drug reward circuitry
伤害感受肽受体信号传导和药物奖赏回路中多巴胺传递的调节
- 批准号:
10112864 - 财政年份:2017
- 资助金额:
$ 23.4万 - 项目类别:
Mechanism and role of G-protein subunit translocation in cell signaling
G蛋白亚基易位在细胞信号传导中的机制和作用
- 批准号:
8502709 - 财政年份:2011
- 资助金额:
$ 23.4万 - 项目类别:
Mechanism and role of G-protein subunit translocation in cell signaling
G蛋白亚基易位在细胞信号传导中的机制和作用
- 批准号:
8320558 - 财政年份:2011
- 资助金额:
$ 23.4万 - 项目类别:
Mechanism and role of G-protein subunit translocation in cell signaling
G蛋白亚基易位在细胞信号传导中的机制和作用
- 批准号:
8203869 - 财政年份:2011
- 资助金额:
$ 23.4万 - 项目类别:
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