Postnatal experience shapes gene expression and connectivity development in the cortex
Postnatal experience shapes gene expression and connectivity development in the cortex
批准号:
10749679
负责人:
Alexander Nevue
金额:
$7.37万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-08-01 至 2026-07-31
关键词:
AccelerationAddressAnatomyArchitectureAuditoryAuditory areaAuditory systemBar CodesBehaviorBiologicalBrainBrain StemCell DeathCell NucleusCell ShapeCellsCentral Nervous SystemChromosome MappingComplexDataDevelopmentDiphtheria ToxinElectrophysiology (science)EngineeringGene ExpressionGeneticGenomicsGoalsHair CellsHearingHomeostasisImpairmentIndividualLabyrinthMapsMeasuresMethodologyMethodsModelingMolecularMolecular GeneticsMusOutcomePathway interactionsProcessPropertyRNARabiesRabies virusResearch PersonnelSamplingSensorySensory DeprivationSensory HairShapesSlideSynapsesTechnical ExpertiseTechniquesTechnologyTherapeutic InterventionTimeTissue-Specific Gene ExpressionTissuesViralbrain cellcareercell cortexcell typediphtheria toxin receptorexcitatory neuronexperiencegenome-widein vivoinhibitory neuronmolecular shapemouse modelneuralneural circuitnew technologynormal hearingnovelpostnatalpostsynaptic neuronspresynapticprogramssensory cortexsensory inputsingle nucleus RNA-sequencingtool
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项目总结
英文摘要
PROJECT SUMMARY
Postnatal sensory experience has a profound effect on the maturation, composition, and connectivity of cortical
cell types, but systematic analyses of these changes have not yet been feasible. This lack of methods for
systematic analysis had made it difficult to define principles in how neural activity re-wires brain circuits and
whether connectivity changes precede or follow molecular changes in brain cell types. Systematically
characterizing how neural activity from the sensory periphery shapes the molecular and synaptic properties of
neural circuits in the brain would benefit from new technologies in which synaptic connectivity relationships and
genome-wide RNAs could be measured in vivo from the same individual cells. High-throughput, single-cell
resolved methods to profile gene expression and synaptic connectivity – including the barcoded rabies virus-
based method called Slide-SBARRO method developed in the Saunders Lab - are well suited to study how
sensory input influences cortical circuit formation. In Aim 1, I will use an inducible mouse model paired with single
nucleus RNA sequencing of primary auditory cortex (A1) cells to determine how auditory input shapes cortical
cell-type proportions and gene expression. In Aim 2, I will determine how auditory input shapes local synaptic
relationships within A1 by reconstructing hundreds of spatially resolved and cell-type-specific monosynaptic
networks using Slide-SBARRO. By comprehensively characterizing how auditory sensory input alters brain cell
and circuit properties in A1, this proposal will enhance our understanding of the mechanisms through which
cortex responds to damage in the sensory periphery. Finally, this proposal will allow me to develop new technical
skills and intellectual approaches that I will use to study auditory circuit plasticity as an independent researcher.
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