Neurotransmitter Interactionson Sub-Second Timescales
亚秒级时间尺度上的神经递质相互作用
基本信息
- 批准号:8507249
- 负责人:
- 金额:$ 18.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:AMPA ReceptorsAddressAgonistAmino Acid NeurotransmittersAnimalsBehaviorBiogenic AminesBiologicalBrainCaliberChemicalsCognitiveControl AnimalDetectionDevelopmentDisease PathwayDopamineEventExcitatory Amino AcidsExposure toFiber OpticsGenerationsGilles de la Tourette syndromeGlutamatesGoalsHuntington DiseaseHydrogen PeroxideKnowledgeLaboratoriesLifeLightMeasurementMeasuresMental DepressionMercuryMethodologyMethodsMicroelectrodesMissionModelingMolecular AnalysisMovement DisordersNatureNervous System PhysiologyNeurobiologyNeuromodulatorNeurotransmittersNitric OxideOrganismParkinson DiseasePathway interactionsPhysiologic pulsePlayRattusResearchResearch PersonnelResolutionRodent ModelRoleScanningSerotoninSignal TransductionSliceSourceSystemTechniquesTechnologyTestingTimeTissuesUltraviolet RaysUnited States National Institutes of HealthWorkaddictionanimal tissueawakebasebrain tissueburden of illnesscarbon fiberdesigndisabilityempoweredextracellulargamma-Aminobutyric Acidhuman diseasein vivoinnovationinsightirradiationmillisecondphotoactivationreceptorresearch studyresponsetooluptake
项目摘要
Ttie particular mechanisms underlying the sub-second control of dopamine release by glutamate and other neurotransmitters/neuromodulators are not well-known largely because the analytical methodology required to address these important questions has not been sufficiently developed. Although one technique, fast-scan cyclic voltammetry at carbon-fiber microelectrodes, offers sufficient temporal resolution to measure the release and uptake of electroactive biogenic amines such as dopamine, its use in characterizing such sub-second neurotransmitter/neuromodulator interactions is lacking. This deficiency represents a serious roadblock because signaling events in the brain that influence outward physical responses and cognitive events occur within this sub-second time regime. Therefore, the central aim of this proposed research is to develop and apply tools that will allow for the quantitative study of these neurotransmitter/neuromodulator interactions in tissues and in vivo. Two temporally-compatible methods, fast-scan cyclic voltammetry and the photoactivation ofthe p-hydroxyphenyl caged form of glutamate (pHP-Glu), used here as a model caged system, will be applied to measure the sub-second response of dopamine release in response to millisecond timescale exposures to exogenous glutamate. The overall objective of this proposed research will be accomplished by successfully completing two specific aims: (1) integrate the sub-second measurement of electrically-evoked dopamine release with the photo-activation of caged compounds in brain slices and (2) optimize the construction and use of a combined probe/carbon-fiber microelectrode for measuring the impact of caged compound photoactivation on dopamine release events in vivo. This approach is innovative because it is among the first to simultaneously apply these two high temporal resolution techniques in living tissues and animals. The development and application of this proposed methodology is significant because it will enable laboratory researchers to measure sub-second timescale dopamine release in response to ¿mu¿s-timescale glutamate application. Moreover, this work should have a broad impact since the application of these techniques can be expanded to include the detection of other electroactive neurotransmitters and neuromodulators, such as serotonin, hydrogen peroxide (H{2}O{2}), and nitric oxide (NO), and the photoactivation of other bioactive molecules, such as GABA and specifically designed synthetic agonists/antagonists. Importantly, this research directly relates to the NIH mission of seeking fundamental knowledge about the nature and behavior of living systems and reducing the burdens of illness and disability in that applies to, but is not limited to: (1) fundamental neurobiological studies; (2) studies of dopamine-related movement disorders [e.g. Huntington's disease (HD), Parkinson's disease (PD), Tourette's syndrome (TS)]; (3) studies of addiction and depression; and (4) studies addressing the mechanisms of action of CNS-active pharmacological agents.
谷氨酸和其他神经递质/神经调质对多巴胺释放的亚秒级控制的具体机制还不为人所知,主要是因为解决这些重要问题所需的分析方法尚未得到充分发展。虽然一种技术,在碳纤维微电极的快速扫描循环伏安法,提供了足够的时间分辨率来测量释放和摄取的电活性生物胺,如多巴胺,其用于表征这种亚秒神经递质/神经调质的相互作用是缺乏的。这种缺陷代表了一个严重的障碍,因为大脑中影响外部身体反应和认知事件的信号事件发生在这个亚秒的时间范围内。因此,这项研究的中心目标是开发和应用工具,将允许这些神经递质/神经调质在组织和体内的相互作用的定量研究。两种时间相容的方法,快速扫描循环伏安法和光活化的对羟基苯基笼状形式的谷氨酸(pHP-Glu),这里使用的模型笼状系统,将被应用于测量响应于毫秒时间尺度暴露于外源性谷氨酸的多巴胺释放的亚秒响应。这项研究的总体目标将通过成功完成两个具体目标来实现:(1)将电诱发多巴胺释放的亚秒测量与脑切片中笼状化合物的光活化相结合;(2)优化组合探针/碳纤维微电极的构建和使用,以测量笼状化合物光活化对体内多巴胺释放事件的影响。这种方法是创新的,因为它是第一个同时应用这两种高时间分辨率技术在活组织和动物。该方法的开发和应用具有重要意义,因为它将使实验室研究人员能够测量响应于μ s时间尺度谷氨酸盐应用的亚秒时间尺度多巴胺释放。此外,这项工作应该有广泛的影响,因为这些技术的应用可以扩展到包括其他电活性神经递质和神经调质,如血清素,过氧化氢(H{2}O{2})和一氧化氮(NO)的检测,以及其他生物活性分子的光活化,如GABA和专门设计的合成激动剂/拮抗剂。重要的是,这项研究直接关系到NIH的使命,即寻求有关生命系统性质和行为的基础知识,并减轻疾病和残疾的负担,适用于但不限于:(1)基础神经生物学研究;(2)多巴胺相关运动障碍[例如,亨廷顿氏病(HD)、帕金森氏病(PD)、抽动秽语综合症(TS)]的研究;(3)成瘾和抑郁症研究;(4)CNS活性药物作用机制研究。
项目成果
期刊论文数量(0)
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Michael A. Johnson其他文献
Comorbidity data collection across different spine registries: an evidence map
不同脊柱登记处的合并症数据收集:证据图
- DOI:
10.1007/s00586-023-07529-3 - 发表时间:
2023 - 期刊:
- 影响因子:2.8
- 作者:
Matthew Quigley;Esther Apos;Trieu;S. Ahern;Michael A. Johnson - 通讯作者:
Michael A. Johnson
Effects of Prior Upper Body Exercise on the 3-min All-Out Cycling Test in Men
先前上半身锻炼对男性 3 分钟全力自行车测试的影响
- DOI:
10.1249/mss.0000000000002395 - 发表时间:
2020 - 期刊:
- 影响因子:4.1
- 作者:
Michael A. Johnson;N. Williams;Ashley W. Graham;Luke A. L. Ingram;S. Cooper;G. Sharpe - 通讯作者:
G. Sharpe
Glass-engraved metasurfaces: the path to ultra-low reflectance, extreme broadband performance, and high acceptance angle for high power laser applications
玻璃雕刻超表面:实现高功率激光应用的超低反射率、极端宽带性能和高接收角的途径
- DOI:
10.1117/12.2641631 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
N. Ray;J. Yoo;Hoang T. Nguyen;Michael A. Johnson;E. Feigenbaum - 通讯作者:
E. Feigenbaum
MEMO PREDICTIVE PID CONTROLS M.H. Moradi
备忘录 预测 PID 控制 M.H.
- DOI:
10.3182/20020721-6-es-1901.00134 - 发表时间:
2002 - 期刊:
- 影响因子:0
- 作者:
M. Katebi;Michael A. Johnson - 通讯作者:
Michael A. Johnson
Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma
成年哮喘患者补充 6·2 和 3·1 g/d 长链 n-3 PUFA 后,呼吸过度引起的支气管收缩和气道炎症标志物明显减少
- DOI:
10.1017/s0007114517001246 - 发表时间:
2017 - 期刊:
- 影响因子:3.6
- 作者:
N. Williams;K. Hunter;D. Shaw;K. Jackson;G. Sharpe;Michael A. Johnson - 通讯作者:
Michael A. Johnson
Michael A. Johnson的其他文献
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{{ truncateString('Michael A. Johnson', 18)}}的其他基金
Neurotransmitter Interactionson Sub-Second Timescales
亚秒级时间尺度上的神经递质相互作用
- 批准号:
8691921 - 财政年份:2014
- 资助金额:
$ 18.39万 - 项目类别:
Methods for Measuring Sub-second Neurotransmitter Interactions
测量亚秒级神经递质相互作用的方法
- 批准号:
8481605 - 财政年份:2012
- 资助金额:
$ 18.39万 - 项目类别:
Methods for Measuring Sub-second Neurotransmitter Interactions
测量亚秒级神经递质相互作用的方法
- 批准号:
8386454 - 财政年份:2012
- 资助金额:
$ 18.39万 - 项目类别:
Simultaneous Analysis of Neurochemical and Behavioral/Cognitive Events In Vivo
体内神经化学和行为/认知事件的同步分析
- 批准号:
8053281 - 财政年份:2010
- 资助金额:
$ 18.39万 - 项目类别:
Simultaneous Analysis of Neurochemical and Behavioral/Cognitive Events In Vivo
体内神经化学和行为/认知事件的同步分析
- 批准号:
7874363 - 财政年份:2010
- 资助金额:
$ 18.39万 - 项目类别:
Neurotransmitter Interactionson Sub-Second Timescales
亚秒级时间尺度上的神经递质相互作用
- 批准号:
8461779 - 财政年份:
- 资助金额:
$ 18.39万 - 项目类别:
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