How do neurons coordinate alternative energy sources to meet the demands of computation?
神经元如何协调替代能源以满足计算需求?
基本信息
- 批准号:10606195
- 负责人:
- 金额:$ 45.34万
- 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:2022-12-01 至 2027-11-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAnatomyAnimalsAxonBehaviorBiochemical PathwayBlood flowBrainBrain imagingCellsCouplesCouplingDendritesDiseaseDrosophila genusElementsEnergy MetabolismEnergy consumptionEnergy-Generating ResourcesEsthesiaExpenditureFunctional Magnetic Resonance ImagingFutureGenesGeneticGlucoseGlycolysisGoalsHumanIn VitroIndividualInvestigationLinkMeasuresMetabolicMetabolic DiseasesMetabolismMethodsMitochondriaModelingMonitorMovementNeurologicNeuronsNeurosciencesOxidative PhosphorylationPathway interactionsPatternPerceptionPhysiologicalPositron-Emission TomographyProductionProxyPublishingPyruvateReactionSensoryShapesSignal TransductionSystemTestingTimeWorkcell typecostenergy balancefluorescence imagingflyimaging modalityin vitro Modelin vivoinsightmetabolic imagingneuralneural patterningneuroimagingneuroregulationneurotransmissionnovel therapeuticsoperationoptogeneticssensorsensory inputsensory stimulusstereotypytherapeutic developmenttwo-photon
项目摘要
Project Summary
How do neurons coordinate alternative energy sources to meet
the demands of neural computation?
PI:Clandinin
The brain is energetically expensive, a metabolic cost that is intrinsic to neural activity and hence a
defining feature of how the brain computes. As a result of this energy intensive operation, the main methods
for measuring changes in neural activity in humans, such as functional magnetic resonance imaging (fMRI),
actually infer neural activity by measuring changes in blood flow, a proxy for local energy consumption.
Moreover, many diseases that alter the efficiency and balance of energy production are characterized by
profound deficits in brain function. However, how neural activity shapes energy production at the level of
individual cells, circuits and across the brain are only incompletely understood, particularly in the context of
active sensation and behavior.
Longstanding work in the field, based in vitro models of single cells and human neuroimaging, have
revealed how different pathways for energy production react to changes in neural activity, responding when
increases in neural activity cause depletion of ATP, a core cellular energy currency. Our recent work using the
intact brain of the behaving fruit fly build on these results, and revealed a new element to the coupling between
metabolism and energy production, namely that cells use current levels of neural activity to predict future
energy needs. Thus, this project seeks to answer how the reactive and predictive elements of neural-metabolic
energy coupling interact.
The proposed work focuses on three key questions. First, do different neuron types, with distinct
patterns of activity in the intact brain, display differences in how they react to, and predict, metabolic load?
Second, how do neurons balance energy production via two alternative energy sources, namely glycolysis and
oxidative phosphorylation, to both react to metabolic cost and predict future expenditures? Finally, how are
these metabolic loads coordinated across circuits in behaving animals detecting sensory stimuli? We
hypothesize that because neuronal activity levels differ substantially across cell types, and because glycolysis
and oxidative phosphorylation can produce ATP with different latencies and efficiencies, subcellular
compartments, neurons and circuits dynamically switch between alternative energy sources to both react to
computational demand and predict future metabolic need. To test this hypothesis, we propose to use two
photon imaging of fluorescent sensors of neural activity and metabolic flux, combined with genetic and
optogenetic perturbations of specific cell types, using the adult fruit fly brain as a model.
As many of the genes involved in energy metabolism are evolutionarily conserved between humans
and flies, deepening our understanding of how neural activity couples to energy metabolism in vivo will
increasing our understanding of the neural impacts of metabolic diseases, possibly opening new therapeutic
avenues for future investigation.
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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Thomas Robert Clandinin其他文献
Thomas Robert Clandinin的其他文献
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{{ truncateString('Thomas Robert Clandinin', 18)}}的其他基金
Population Neural Activity Mediating Sensory Perception Across Modalities
群体神经活动介导跨模态的感官知觉
- 批准号:
10310712 - 财政年份:2021
- 资助金额:
$ 45.34万 - 项目类别:
Population Neural Activity Mediating Sensory Perception Across Modalities
群体神经活动介导跨模态的感官知觉
- 批准号:
10242189 - 财政年份:2018
- 资助金额:
$ 45.34万 - 项目类别:
Population Neural Activity Mediating Sensory Perception Across Modalities
群体神经活动介导跨模态的感官知觉
- 批准号:
9789712 - 财政年份:2018
- 资助金额:
$ 45.34万 - 项目类别:
A Brain Circuit Program for Understanding the Sensorimotor Basis of Behavior
用于理解行为的感觉运动基础的脑回路程序
- 批准号:
10202757 - 财政年份:2017
- 资助金额:
$ 45.34万 - 项目类别:
Revealing circuit control of neuronal excitation with next-generation voltage indicators
使用下一代电压指示器揭示神经元兴奋的电路控制
- 批准号:
9380741 - 财政年份:2017
- 资助金额:
$ 45.34万 - 项目类别:
A Brain Circuit Program for Understanding the Sensorimotor Basis of Behavior
用于理解行为的感觉运动基础的脑回路程序
- 批准号:
9444301 - 财政年份:2017
- 资助金额:
$ 45.34万 - 项目类别:
Project 3: Neural Basis of Motion Guidance Loops
项目 3:运动引导环的神经基础
- 批准号:
10202763 - 财政年份:2017
- 资助金额:
$ 45.34万 - 项目类别:
A new strategy for cell-type specific gene disruption in flies and mice
果蝇和小鼠细胞类型特异性基因破坏的新策略
- 批准号:
9297370 - 财政年份:2015
- 资助金额:
$ 45.34万 - 项目类别:
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