Identifying pathways for motor variability in the mammalian brain
Identifying pathways for motor variability in the mammalian brain
批准号:
8955334
负责人:
Jesse Heymann Goldberg
金额:
$241.5万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-09-30 至 2020-06-30
关键词:
AddressAnimalsBehaviorBehavioralBehavioral ParadigmBiological ModelsBrainChoreaComplexComputersDystoniaEffectivenessElementsEventForelimbFunctional disorderGeneticJoystickLearningMotorMotor CortexMotor PathwaysMotor outputMovementMusOpsinPathway interactionsPositioning AttributePosturePrimatesProcessResolutionSpecificityStagingSystemTestingTimeTouch sensationTrainingTransgenic MiceWorkbehavior influencebrain pathwaycell typehigh throughput analysismillisecondmind controlmotor controlmotor learningnervous system disorderneural circuitnew technologynext generationoptogeneticspublic health relevancerelating to nervous systemresearch studyskillsspatiotemporaltargeted treatmenttool
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Deficits in movement initiation, control and variability constitute the core dysfunctions of neurological disease, but we still don't know how these processes are implemented in the brain. The main obstacle is the sheer complexity of brain pathways for movement. The mammalian motor system is a distributed group of neural circuits, which are in turn comprised of complex microcircuits and specific cell types. Because we don't know how these small circuit elements influence behavior, current treatments lack effectiveness and specificity. To address this problem, we developed a panel of new technologies that will allow us to define how previously inaccessible microcircuits control motor behavior. First, we invented a touch-sensing joystick that quantifies mouse forelimb trajectories with unprecedented (micron-millisecond) spatiotemporal resolution. Second, we incorporate this joystick into automated, computer-controlled homecages that perform real-time behavioral analysis and high-throughput behavioral training. Third, we devise a new way of doing high-throughput optogenetics in untethered mice using newly available red-shifted opsins. Finally, we demonstrate for the first time that mice can learn complex center-out forelimb tasks similar to ones long used in primates. By establishing a new, sophisticated motor learning paradigm in mice - a tractable model system with powerful genetic tools - we are now poised to selectively manipulate neural activity in large batches of behaving animals. First, we will perform projection-specific optogenetic silencing to determine how each of fourteen pathways converging on mouse forelimb motor cortex controls movement initiation and variability in the joystick trajectories. Next, we will use Cre-transgenic mouse lines to test how distinct layers inside forelimb cortex differentially control these processes. For both of these experiments, real-time behavioral analysis will enable optogenetic manipulations to be time-locked to specific task events and animal postures, as well as at distinct stages of skill learning. In summary, the proposed work combines unprecedented readout of motor output with unprecedented tools for manipulating previously inaccessible parts of the mammalian motor system. Our new behavioral and experimental paradigm will identify yet-to-be discovered circuits controlling movement initiation, variability and learning. If successful, it will no longer be so mysterious where tremos, dystonias, akinesias and choreas come from. We will be able to point to specific pathways and cell types positioned to cause specific deficits, which in turn will provide a roadmap towards the next generation of more targeted therapies.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1038/s41586-021-03561-9
发表时间:
2021-06
期刊:
Nature
影响因子:
64.8
作者:
[Bollu T, Ito BS, Whitehead SC, Kardon B, Redd J, Liu MH, Goldberg JH]
通讯作者:
Goldberg JH
Neural Mechanisms of Social Communication in Parrots
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批准号:10207958
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项目类别:
-
资助金额:$68.92万
-
财政年份:2021
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负责人:Jesse Heymann Goldberg
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依托单位:
MOTES: Micro-scale Opto-electronically Transduced Electrode Sites
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批准号:9244414
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项目类别:
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资助金额:$28.18万
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财政年份:2016
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负责人:Jesse Heymann Goldberg
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依托单位:
MOTES: Micro-scale Opto-electronically Transduced Electrode Sites
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批准号:9360613
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项目类别:
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资助金额:$20.13万
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财政年份:2016
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负责人:Jesse Heymann Goldberg
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依托单位:
Neural Mechanisms of Performance Evaluation During Motor Sequence Learning
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批准号:10183339
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项目类别:
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资助金额:$36.9万
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财政年份:2015
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负责人:Jesse Heymann Goldberg
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依托单位:
Neural mechanisms of performance evaluation during motor sequence learning
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批准号:9306224
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项目类别:
-
资助金额:$34.06万
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财政年份:2015
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负责人:Jesse Heymann Goldberg
-
依托单位:
Neural Mechanisms of Performance Evaluation During Motor Sequence Learning
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批准号:10658875
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项目类别:
-
资助金额:$36.9万
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财政年份:2015
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负责人:Jesse Heymann Goldberg
-
依托单位:
Neural mechanisms of performance evaluation during motor sequence learning
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批准号:9136884
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项目类别:
-
资助金额:$33.73万
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财政年份:2015
-
负责人:Jesse Heymann Goldberg
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依托单位:
Neural mechanisms of performance evaluation during motor sequence learning
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批准号:9753376
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项目类别:
-
资助金额:$33.95万
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财政年份:2015
-
负责人:Jesse Heymann Goldberg
-
依托单位:
Neural Mechanisms of Performance Evaluation During Motor Sequence Learning
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批准号:10437774
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项目类别:
-
资助金额:$36.9万
-
财政年份:2015
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负责人:Jesse Heymann Goldberg
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依托单位:
Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning
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批准号:8711569
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项目类别:
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资助金额:$24.81万
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财政年份:2010
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负责人:Jesse Heymann Goldberg
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依托单位:
Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning
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批准号:8045232
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项目类别:
-
资助金额:$13.27万
-
财政年份:2010
-
负责人:Jesse Heymann Goldberg
-
依托单位:
Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning
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批准号:8539852
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项目类别:
-
资助金额:$24.05万
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财政年份:2010
-
负责人:Jesse Heymann Goldberg
-
依托单位:
Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning
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批准号:8136045
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项目类别:
-
资助金额:$13.67万
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财政年份:2010
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负责人:Jesse Heymann Goldberg
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依托单位:
Basal Ganglia-Thalamic Interactions in Behaving Songbirds During Learning
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批准号:8531556
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项目类别:
-
资助金额:$24.9万
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财政年份:2010
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负责人:Jesse Heymann Goldberg
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依托单位:
海外基金