RP3: Cell Phenotyping: Intrinsic physiology and genetic characteristics

RP3:细胞表型:内在生理学和遗传特征

基本信息

  • 批准号:
    10011920
  • 负责人:
  • 金额:
    $ 70.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-09-15 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Summary: Project 3 – Cell Phenotyping: Intrinsic Physiology and Genetic Characteristics The identification of developmental pathways and neuronal subtype markers has made circuit studies of the spinal cord one of the most tractable CNS systems to investigate how neural networks control behaviorally relevant activity. Although a general framework now exists for labeling cardinal interneuron and motor neuron populations within the ventral spinal cord using Cre-mouse lines, it is apparent that each cardinal spinal neuron population is in fact a complex mixture of many heterogeneous cell types when viewed from the perspective of inputs, outputs, firing properties, and molecular-genetic attributes. Despite clear evidence for this heterogeneity, the relationship between each of these cellular properties is very fragmentary. The goal of Project 3 is to interrelate how cell lineage (cardinal neuron identity), connectivity to motor pools, intrinsic firing properties, and molecular genetics define cell types to provide a true definition of cell identity. This interconnected framework of cell features is critical because it will allow modeling to predict how spinal circuitry modulates the control of movement, and it will serve as the basis for genetic experiments that perturb neuronal function in order to test predictions of the model. This U19 Spinal Cord Circuit Team hypothesizes that the heterogeneity among premotor interneurons will scale with the complexity of motor functions mediated by different motor pools. If this hypothesis is correct, muscle groups controlling the wrist will be controlled by a more diverse population of premotor interneurons than the subset controlling the elbow because the degrees of freedom in movement differ between these two joints. There are two main approaches that will be employed to define interneuron heterogeneity: patch clamp electrophysiology in order to define input/output relationships, and single cell sequencing transcriptomics (scRNAseq) to define molecular heterogeneity. These methods will be anchored to connectivity and lineage by recording and sequencing cells that have been Cre-tagged to mark their lineage of origin (i.e. V1, V2a, V2b, V3) and retrograde trans-synaptically labeled with rabies to identify motor pool connectivity. How will the characterization of cell type-specific intrinsic firing patterns and transcriptome be applied to the broader understanding of neuroscience and limb movements in particular? First, each cardinal interneuron group will be divided into many additional subtypes based on their unique combinatorial patterns of gene expression. However, the goal is not to attempt to fractionate the cardinal interneuron groups into as many subpopulations as possible, rather it is to establish a set of molecular landmarks that can be used to reliably identify and genetically perturb subsets of interneurons with known firing patterns and connectivity. It is only with information about cell numbers, connectivity, synaptic strength, firing properties, and “surgical” molecular tools to perturb neuronal subtype activity can models of cervical spinal circuitry be created and functionally tested to understand how forelimb movements are regulated.
项目3 -细胞表型:内在生理和遗传特征

项目成果

期刊论文数量(0)
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专利数量(0)

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SAMUEL L. PFAFF其他文献

SAMUEL L. PFAFF的其他文献

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{{ truncateString('SAMUEL L. PFAFF', 18)}}的其他基金

Characterization of spinal circuits underlying motor synergy function
运动协同功能背后的脊髓回路的表征
  • 批准号:
    10281130
  • 财政年份:
    2021
  • 资助金额:
    $ 70.9万
  • 项目类别:
Characterization of spinal circuits underlying motor synergy function
运动协同功能背后的脊髓回路的表征
  • 批准号:
    10687832
  • 财政年份:
    2021
  • 资助金额:
    $ 70.9万
  • 项目类别:
Characterization of spinal circuits underlying motor synergy function
运动协同功能背后的脊髓回路的表征
  • 批准号:
    10478289
  • 财政年份:
    2021
  • 资助金额:
    $ 70.9万
  • 项目类别:
MiR-218 regulatory networks in adult mice and its relationship to ALS
成年小鼠的 MiR-218 调控网络及其与 ALS 的关系
  • 批准号:
    10196817
  • 财政年份:
    2021
  • 资助金额:
    $ 70.9万
  • 项目类别:
Tools for regulated expression control of miR-218
用于调控 miR-218 表达控制的工具
  • 批准号:
    10196829
  • 财政年份:
    2021
  • 资助金额:
    $ 70.9万
  • 项目类别:
RP3: Cell Phenotyping: Intrinsic physiology and genetic characteristics
RP3:细胞表型:内在生理学和遗传特征
  • 批准号:
    10226043
  • 财政年份:
    2019
  • 资助金额:
    $ 70.9万
  • 项目类别:
RP3: Cell Phenotyping: Intrinsic physiology and genetic characteristics
RP3:细胞表型:内在生理学和遗传特征
  • 批准号:
    10696198
  • 财政年份:
    2019
  • 资助金额:
    $ 70.9万
  • 项目类别:
RP3: Cell Phenotyping: Intrinsic physiology and genetic characteristics
RP3:细胞表型:内在生理学和遗传特征
  • 批准号:
    9815389
  • 财政年份:
    2019
  • 资助金额:
    $ 70.9万
  • 项目类别:
Novel mechanistic study of CMT2D neuropathy
CMT2D 神经病的新机制研究
  • 批准号:
    8656827
  • 财政年份:
    2013
  • 资助金额:
    $ 70.9万
  • 项目类别:
Novel mechanistic study of CMT2D neuropathy
CMT2D 神经病的新机制研究
  • 批准号:
    8572006
  • 财政年份:
    2013
  • 资助金额:
    $ 70.9万
  • 项目类别:

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