The Function of Sleep in Critical Period Plasticity
睡眠在可塑性关键期的作用
基本信息
- 批准号:10590177
- 负责人:
- 金额:$ 9.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdultAlgorithmsAnimalsAstrocytesAttention Deficit DisorderAttentional deficitBehaviorBehavioralBehavioral AssayBiological AssayBody partBrainCarbon DioxideCategoriesCellsChronicCognition DisordersComputer ModelsComputer softwareCoupledDataData SetDevelopmentDrosophila genusElderlyElectrophysiology (science)EnvironmentExhibitsExposure toFacultyFoundationsGene Expression ProfilingGenesGeneticGoalsHumanImageInhibitory SynapseInterneuronsLifeLobeMachine LearningManualsMediatingMentorsMethodsMolecularMorphologyMuscleNeurodevelopmental DisorderNeuronal PlasticityNeuronsOlfactory PathwaysPhysiologicalPlayPositioning AttributeProcessRNA interference screenResearchResourcesRiskRoleScientistShapesSignal TransductionSleepSleep DeprivationSleep StagesSleep disturbancesStatistical MethodsStatistical ModelsSynapsesSystemTestingTrainingUniversitiesWorkadverse outcomeautism spectrum disorderbehavioral habituationbehavioral phenotypingcareercareer developmentcell typecritical periodearly childhoodexperienceexperimental studyflyimaging modalityin vivojuvenile animalknock-downmarkov modelmembermodel organismneuralneural circuitneurobehavioral disorderneurocognitive disorderneurophysiologynew therapeutic targetnoveloptogeneticspatch clamppostsynaptic neuronspresynaptic neuronspreventprogramsresearch and developmentsingle-cell RNA sequencingsocial deficitstenure track
项目摘要
Project Summary
Although we spend a third of our lives sleeping, the function of this evolutionarily conserved behavior
remains elusive. Most studies investigating the function of sleep have focused on sleep in adults.
However, young animals spend an even greater proportion of their lives asleep, and their sleep is
deeper and has distinct electrophysiological features. Sleep in young animals is thought to aid brain
development by promoting plasticity. These plastic processes occur during critical periods in which
neural circuits are shaped by experience. Yet, the molecular, cellular and circuit mechanisms by
which sleep functions in critical period plasticity remains elusive. This proposal aims to address this
question by using a simple neural circuit in a genetically tractable model organism. In Aim 1, I will
define sleep substages using behavioral features and statistical modeling, as well as imaging
methods, and then determine if critical period plasticity requires a specific form of sleep. In Aim 2, I
will investigate the neurophysiological processes by which sleep promotes critical period plasticity
using patch clamp electrophysiology and investigate the genes that are important for this process
using single cell RNA sequencing. In Aim 3, I will perform a large-scale RNAi screen using a
behavioral assay to find novel genes that are involved in sleep-dependent critical period plasticity. In
addition, I will investigate whether sleep-related neural activity is generated by astrocytes to aid
critical period plasticity. Overall, these aims will delineate the function of specific sleep states in young
animals and identify cellular and molecular mechanisms underlying sleep-dependent critical period
plasticity. Because sleep disturbances in early life are predictors of neurocognitive disorders such as
autism and attention deficit disorders, this work may have implications for the treatment of
neurodevelopmental conditions. To achieve these aims, I have brought together a mentoring team
which includes experts in computational modeling, transcriptional profiling, and developmental neural
plasticity. In addition, the proposed career development and research plan will capitalize on the
exceptional environment, facilities, and resources that Johns Hopkins University provides. My
overarching career goal is to obtain a tenure track faculty position and establish my own research
program as an independent scientist, and the proposed work and training will form a strong
foundation for achieving this goal.
项目摘要
尽管我们一生中有三分之一的时间都在睡觉,
仍然难以捉摸大多数关于睡眠功能的研究都集中在成年人的睡眠上。
然而,年轻的动物花费更大比例的时间在睡眠中,他们的睡眠是
具有明显的电生理特征。年轻动物的睡眠被认为有助于大脑
通过促进可塑性发展。这些塑性过程发生在关键时期,
神经回路是由经验塑造的。然而,分子,细胞和电路机制,
睡眠在关键期的可塑性中起着什么样的作用仍然是一个谜。该提案旨在解决这一问题
问题通过使用一个简单的神经回路在遗传上听话的模式生物。在目标1中,我将
使用行为特征和统计建模以及成像来定义睡眠子阶段
方法,然后确定关键期可塑性是否需要特定形式的睡眠。在目标2中,我
将研究睡眠促进关键期可塑性的神经生理过程
使用膜片钳电生理学,并研究在这一过程中重要的基因,
使用单细胞RNA测序。在目标3中,我将使用一个大规模的RNAi筛选,
行为分析,以寻找参与睡眠依赖性关键期可塑性的新基因。在
此外,我将研究是否睡眠相关的神经活动产生的星形胶质细胞,以帮助
临界期塑性总的来说,这些目标将描绘出年轻人特定睡眠状态的功能。
动物,并确定睡眠依赖性关键期的细胞和分子机制
可塑性因为早期的睡眠障碍是神经认知障碍的预测因子,
自闭症和注意力缺陷障碍,这项工作可能对治疗
神经发育状况为了实现这些目标,我组建了一个指导团队,
包括计算建模、转录谱分析和发育神经系统方面的专家,
可塑性此外,拟议的职业发展和研究计划将利用
约翰霍普金斯大学提供的卓越环境、设施和资源。我
总体职业目标是获得终身教职,并建立自己的研究
计划作为一个独立的科学家,和建议的工作和培训将形成一个强大的
为实现这一目标奠定了基础。
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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