Hemogenetic imaging technology for circuit-specific analysis of primate brain function
用于灵长类大脑功能电路特异性分析的血遗传学成像技术
基本信息
- 批准号:10652546
- 负责人:
- 金额:$ 60.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimalsAreaAutopsyBehavioralBrainBrain regionCalcium SignalingCallithrixCategoriesCellsCognitiveCollaborationsComplementComputer ModelsDataDependenceDependovirusDiseaseElectrophysiology (science)ElementsExhibitsFaceFacultyFamilyFunctional ImagingFunctional Magnetic Resonance ImagingGenerationsGoalsGrainHumanImageImaging technologyIndividualInjectionsInvestigationLaboratoriesLiteratureLongitudinal StudiesLuciferasesMacacaMagnetic Resonance ImagingMeasurementMeasuresMethodologyMethodsMonitorMonkeysNeurobiologyNeuronsNeurosciences ResearchOutputPatternPerformancePharmaceutical PreparationsPopulationPrimatesPropertyProtein EngineeringProteinsReporterReproducibilityResolutionRodentSensorySignal TransductionSourceStimulusStreamSurveysTechniquesTechnologyTestingTrainingValidationVariantViralViral PackagingViral VectorVirusVisualVisual CortexVisual PathwaysVisual SystemVisualizationWorkbioluminescence imagingcell typedelivery vehicledesignexperimental studyhemodynamicsimaging probeimprovedin vivoneuralneural circuitneurotoxicitynonhuman primateoperationresponseretrograde transportside effecttechnology developmenttoolvalidation studiesvectorvisual processingvisual stimulus
项目摘要
Primate brains contain cortical areas that exhibit selective engagement in high-level sensory or behavioral
operations. The functional specialization of these regions is thought to be central to primate-specific cognitive
faculties and to associated disorders. Deciphering the origins of functional specialization in primate brain regions
has been an enormously challenging task, however, due in large part to the absence of suitable experimental
tools. To address this problem, we will develop a method for measuring the activity of inputs to specialized areas
from throughout the brain, permitting systematic analyses of information flow in the multiregional neural circuitry
that gives rise to high-level functions. Our method will employ a conceptually new family of genetically encoded
imaging probes called NOSTICs, which transduce the calcium signaling of NOSTIC-expressing neurons into
localized hemodynamic signals that can be dynamically monitored using brain-wide measurement techniques
like functional magnetic resonance imaging (fMRI). When delivered using retrogradely transported viral vectors,
NOSTICs can permit targeted fMRI-based recording of neural activity in distributed cell populations that provide
monosynaptic input to any injection target in the brain. In our preliminary work, we have created first-generation
NOSTIC probes and used them to demonstrate genetically targeted functional imaging in rodents. In Aim 1 of
this project, we will take two steps that adapt this tool for use in nonhuman primates. We will create second-
generation NOSTICs that display improved performance for circuit-specific functional imaging, while also devel-
oping viral vectors that allow expression of these probes to be tracked longitudinally in primate brains. We will
also adapt the NOSTIC probes for incorporating into adeno-associated viruses, which provide extended capa-
bility compared with the herpes viruses we currently use. In Aim 2, we will perform pilot experiments to investigate
whether NOSTICs can provide circuit-specific readouts in nonhuman primates. These tests will already be pos-
sible using our currently available probes and vectors, and new variants from Aim 1 will also be tested when
available. Successful demonstration of NOSTIC functionality for circuit imaging in marmosets constitutes our
proposed go/no-go criterion for entry into the UH3 stage of this project. Then in Aim 3 (UH3 stage), we will
validate NOSTIC probes in two paradigms that explore their performance across brain regions, experimental
contexts, and primate species. In the first paradigm, we will apply NOSTICs to examine origins of functional
specialization in face-selective regions of the marmoset brain. In the second paradigm, we will apply NOSTICs
to investigate brain-wide contributions to object selective responses in the ventral stream of the macaque visual
cortex. These experiments will be performed as multi-laboratory collaborations that both harness and dissemi-
nate the NOSTIC technology; this work will therefore establish a broadly applicable transformative approach for
mechanistic analysis of primate brain function.
灵长类动物的大脑包含皮层区域,表现出选择性参与高级感觉或行为
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Alan Jasanoff其他文献
Alan Jasanoff的其他文献
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{{ truncateString('Alan Jasanoff', 18)}}的其他基金
Analysis of integrated brain functions using hemogenetic imaging
使用血遗传学成像分析大脑的综合功能
- 批准号:
10365025 - 财政年份:2022
- 资助金额:
$ 60.31万 - 项目类别:
Analysis of Integrated Brain Functions Using Hemogenetic Imaging
使用血遗传学成像分析大脑的综合功能
- 批准号:
10553193 - 财政年份:2022
- 资助金额:
$ 60.31万 - 项目类别:
Multimodal probes for multiscale calcium imaging
用于多尺度钙成像的多模态探针
- 批准号:
10154098 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
Hemogenetic imaging technology for circuit-specific analysis of primate brain function
用于灵长类大脑功能电路特异性分析的血遗传学成像技术
- 批准号:
10271639 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
Hemogenetic imaging technology for circuit-specific analysis of primate brain function
用于灵长类大脑功能电路特异性分析的血遗传学成像技术
- 批准号:
10478067 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
Nanosensors for sensitive brain-wide neurochemical imaging
用于敏感全脑神经化学成像的纳米传感器
- 批准号:
10154138 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
Toward functional molecular neuroimaging using vasoactive probes in human subjects
在人类受试者中使用血管活性探针进行功能性分子神经成像
- 批准号:
10253338 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
Supplement to Neurobiological Engineering Training Program
神经生物工程培训计划的补充
- 批准号:
10836872 - 财政年份:2021
- 资助金额:
$ 60.31万 - 项目类别:
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