Circadian Structural Plasticity in Central Pacemakers
中央起搏器的昼夜节律结构可塑性
基本信息
- 批准号:10409826
- 负责人:
- 金额:$ 51.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-30 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalARNTL geneAddressAdhesionsAdultAnimalsArgentinaAstrocytesAutomobile DrivingBehaviorBehavioralBiological ModelsBrainCalciumCell CommunicationCellsCircadian RhythmsConfocal MicroscopyCountryCoupledCuesDrosophila genusElectron MicroscopyEnterobacteria phage P1 Cre recombinaseFaceFeedbackFiberFlavoproteinsGeneticGenetic TranscriptionHypothalamic structureImmunohistochemistryImpairmentInjectionsLabelMammalsMediatingMolecularMotor ActivityMusNeuritesNeurogliaNeuronsNeuropeptidesNeurotransmittersOrganismPacemakersPeriodicityPhotoperiodPhysiologicalPigmentsPostdoctoral FellowPrincipal InvestigatorProcessPropertyReporterReportingResearchScanning Electron MicroscopySignal TransductionSleep Wake CycleSliceStructureStudentsSynapsesSynaptophysinSystemTechniquesTestingTimeTissuesTrainingTranslationsVasoactive Intestinal PeptideViralVirusVisualizationcircadiancircadian pacemakerdensityex vivo imagingexperienceexperimental studyflygene productimmunocytochemistryknock-downlight microscopylongitudinal analysismouse Cre recombinaseneuronal circuitrypolymerizationpostsynapticpresynapticpromoterreceptorreconstitutionrecruitresponsesuprachiasmatic nucleustoolvector
项目摘要
SUMARY
Circadian rhythms depend on the molecular transcription/translation negative feedback loop (TTL) operating in
clock neurons, and on the network properties of these neurons. Among the properties that could be recruited
by the circadian clock are changes in the identity of pre/post synaptic partners and/or strength of the
connectivity between clock neurons, a property collectively termed as circadian structural plasticity. Our central
hypothesis is that circadian structural plasticity within the central circadian clocks of mammals and Drosophila
are part of the time-encoding mechanisms. We will employ mouse and fly genetics combined with state-of-the-
art quantitative 3D light and electron microscopy techniques to address the extent of structural plasticity within
specific neurons of the mouse suprachiasmatic nucleus (SCN) and the Drosophila circadian network.
Specific aim 1 will assess how widespread structural plasticity is in the Drosophila circadian network as well as
which are the functional consequences of those structural changes. We will explore the extent of circadian
neuronal remodeling of subsets of PDF and non-PDF pacemaker neurons using CM and SBEM (sub-aims 1A i
and ii). We will examine time-of-day dependent functional connectivity changes among clock neurons through
chemogenetic GCamP6-reporting (sub-aim 1B). Sub-aim 1C will examine the behavioral consequences of
impairing structural remodeling; sub-aim 1D will further investigate the molecular mechanisms underlying
circadian structural plasticity.
Specific aim 2 will examine the degree of circadian structural remodeling in SCN VIPergic neurons, which are
an essential component of the timekeeping mechanism, through virally mediated sparse-labeling (CM) (sub-
aim 2A), or serial block-face scanning electron microscopy (SBEM) with a marker that enables the analysis of
dendritic ultrastructure (sub-aim 2C). Finally, we will assess if circadian oscillations in VIP neuronal processes
rely on the TTL by repeating experiments in 1A in VIP-specific Bmal1-/- mice (sub-aim 2B).
Specific aim 3 will explore if connectivity of VIPergic neurons changes throughout the 24-h cycle. Using GFP
reconstitution across synaptic partners (GRASP), we will investigate if these connections change with circadian
time through immunocytochemistry and CM analysis in fixed tissue (sub-aim 3A) as well as ex vivo in SCN
slices (sub- aim 3B). We will also determine whether GRASP-detected rhythms depend on the canonical TTL
by repeating experiments in 2A and 2B in VIP- or SCN astrocyte-specific Bmal1-/- mice (sub-aim 3C).
Our experiments test predictions of the hypothesis that circadian structural plasticity represents a defining
feature of central neuronal circadian pacemakers. Support for this hypothesis would provide a critical new
perspective to understand how these pacemakers encode time at the network level. Furthermore, the
experiments we propose represent a unique opportunity for research capacity building in Argentina, where the
foreign principal investigator is located, and where students and postdocs will be trained in techniques that are
still not fully developed in that country.
SUMARY
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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Maria Fernanda Ceriani其他文献
Maria Fernanda Ceriani的其他文献
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{{ truncateString('Maria Fernanda Ceriani', 18)}}的其他基金
Circadian Structural Plasticity in Central Pacemakers
中央起搏器的昼夜节律结构可塑性
- 批准号:
10630311 - 财政年份:2020
- 资助金额:
$ 51.45万 - 项目类别:
Circadian Structural Plasticity in Central Pacemakers
中央起搏器的昼夜节律结构可塑性
- 批准号:
10266132 - 财政年份:2020
- 资助金额:
$ 51.45万 - 项目类别:
Circadian control of structural plasticity in Drosophila
果蝇结构可塑性的昼夜节律控制
- 批准号:
8085756 - 财政年份:2010
- 资助金额:
$ 51.45万 - 项目类别:
Circadian control of structural plasticity in Drosophila
果蝇结构可塑性的昼夜节律控制
- 批准号:
8250791 - 财政年份:2010
- 资助金额:
$ 51.45万 - 项目类别:
Circadian control of structural plasticity in Drosophila
果蝇结构可塑性的昼夜节律控制
- 批准号:
7855493 - 财政年份:2010
- 资助金额:
$ 51.45万 - 项目类别:
Mechanisms of progressive neurodegeneration: combining forward genetic screens in
进行性神经变性的机制:结合正向遗传筛选
- 批准号:
8053114 - 财政年份:2009
- 资助金额:
$ 51.45万 - 项目类别:
Mechanisms of progressive neurodegeneration: combining forward genetic screens in
进行性神经变性的机制:结合正向遗传筛选
- 批准号:
7914324 - 财政年份:2009
- 资助金额:
$ 51.45万 - 项目类别: