Realization of Optical Cell-based Reporters for in vivo Detection of Neuropeptides
Realization of Optical Cell-based Reporters for in vivo Detection of Neuropeptides
批准号:
9213616
负责人:
David Kleinfeld
金额:
$99.69万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-09 至 2019-06-30
关键词:
AcetylcholineAddressAnimalsBedsBehaviorBlood VesselsBlood flowBrainCalciumCellsCognitionColorComplexCorpus striatum structureCorticotropin-Releasing HormoneCoupledDetectionDevelopmentDiffuseDopamineDynorphinsElectrophysiology (science)EngineeringFluorescenceFluorescence Resonance Energy TransferG-Protein-Coupled ReceptorsGTP-Binding ProteinsGenetic studyImplantInflammationLaboratoriesLeadLearningLettersLightLongitudinal StudiesMeasurementMeasuresMental DepressionMental HealthMental disordersMigraineModelingMolecular BiologyMolecular GeneticsMonitorMotivationMusNatureNervous system structureNeuromodulatorNeuronal PlasticityNeuronsNeuropeptide ReceptorNeuropeptidesNeurotransmittersNorepinephrineOpticsPeptidesPharmaceutical PreparationsPhysiologicalPhysiologyPlayProcessRegulationReporterResearch Project GrantsResolutionRespirationRhodopsinRodentRoleSignal TransductionSiteSleepSliceSomatostatinSpecificityStressSubstance PSynapsesTechniquesTestingTimeValidationVasoactive Intestinal Peptideaddictionawakebasebrain dysfunctioncalcium indicatorconstrictiondesignhypocretinin vitro testingin vivoin vivo imaginginnovationmedical schoolsnanomolarneural circuitneuropeptide Yneuroregulationnew technologyreceptorrelating to nervous systemresponsesensorsleep regulationsmall moleculetemporal measurementtooltransmission process
中文摘要
项目总结
英文摘要
Project Summary
Neuropeptides are essential neuromodulators in the brain. They are released into the extrasynaptic space,
where they diffuse over long distances and signal through G protein coupled neuropeptide receptors.
Neuropeptides control cognition, sensorimotor processing, and energetics through changes in vascular tone
and blood flow in the nervous system. Pharmacological and molecular genetic studies have implicated
alterations in neuropeptide signaling as a contributor to brain dysfunctions, including migraines, addiction,
motivation and stress. Although widely expressed in the brain, remarkably little is known about when and
where neuropeptides are released. Monitoring the release of neuropeptides in real-time in awake animals
performing complex behaviors would be transformative, enabling the elucidation of the function of
neuropeptides in regulating neural circuits in the brain.
In response to RFA-MH-16-775, we propose to develop and validate an innovative neurotechnique for
optically measuring release of neuropeptides in a cell-specific and circuit-specific processes in the brain. The
new technology is based on cell-based neurotransmitter fluorescent engineered reporters, referred to as
CNiFERs, which were original developed for detecting the release of classical, small molecule
neurotransmitters. A CNiFER is a clonal HEK293 cell that is engineered to express a specific G-protein
coupled receptor and a genetically encoded fluorescence-based intracellular calcium sensor. CNiFERs are
implanted in the brain, where they produce minimal inflammation and remain viable for days, and have been
used successfully to measure volume transmission of dopamine, norepinephrine and acetylcholine in vivo
during learning.
Three neuropeptide CNiFERs will be developed and used for test-bed validation projects within our own
laboratories: Orexin, which is important in sleep regulation as well as drug seeking and reinstatement,
Somatostatin which has been implicated in depression, motivation and learning, and Vasoactive Intestinal
Peptide, which as been implicated in neuroplasticity and learning. For collaborative projects, we will further
construct four additional neuropeptide CNiFERs for detecting release of Dynorphin, Corticotropin-Releasing
Factor, Neuropeptide Y and Substance P. Each neuropeptide CNiFER will be subjected to rigorous in vitro
testing prior to their use to study the dynamics and consequences of release of neuropeptides in vivo.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
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Optogenetic mapping of synaptic activity and control of intracellular signaling
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Optogenetic mapping of synaptic activity and control of intracellular signaling
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依托单位:
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依托单位:
海外基金