GABA Driven Depolarization in Early Human Cortical Development.

GABA 驱动早期人类皮质发育中的去极化。

基本信息

  • 批准号:
    9317257
  • 负责人:
  • 金额:
    $ 27.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2019-03-31
  • 项目状态:
    已结题

项目摘要

Project Summary: Human pluripotent stem cells provide an attractive experimental platform for studying the normal and abnormal development of human neural networks. In vitro, induced pluripotent stem cells (iPSC) have been used to study early developmental mechanisms and the initial stages of synaptogenesis and circuit formation. iPSC also offer the tantalizing but unrealized potential to study human neural circuits in vitro. Our efforts to model the development of human cortical circuits in vitro indicate that differentiation can be segmented into a 5-step progression involving: 1) patterning of the neuroectoderm and early neurogenesis - robustly evident after 3 weeks; 2) neuroblast migration and initial differentiation into regionally-specific neuronal subtypes - evident after 6 weeks; 3) development of spontaneous electrical activity and early synaptogenesis – evident after 2-3 months; 4) initial appearance of astrocytes and the formation of vigorous and synchronous oscillatory bursting within large ensembles – evident within 3-5 months; 5) resolution of large hypersynchronous neuronal ensembles into smaller, discreetly firing sub-ensembles – occasionally observed after more than 6 months. Appearance of oligodendrocyte progenitors and myelination of axons seen in vivo has not yet been observed or reported. Although it is comforting to confirm that human-specific developmental programs are temporally intact in iPSC models, the protracted timeline makes it challenging to study late developmental mechanisms or mature circuit function. The ultimate goal of this project is to develop methods to accelerate the formation of networks of highly interconnected human neurons with mature synapses. Synchronized and oscillatory neuronal activity appears to be a fundamental and obligate transitional property of developing nervous systems. Young neurons in structures as diverse as retina, cerebral cortex and spinal cord experience periods of high connectivity and robust neuronal activity that are subsequently refined to produce specific synaptic connections and regulated action potential activity. Human neurons developing in vitro presumably require the acquisition of these same properties in order to become functional neuronal networks. Our preliminary work suggests that these obligate properties are acquired by the interactions of cell types generated at different times in development and/or from different regions of the developing brain. Experiments in this proposal focus on novel methods that recapitulate these interactions to accelerate the acquisition of synchronous oscillatory bursting and promote the further maturation of iPSC-derived human neural networks.
项目总结:

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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Theo D Palmer其他文献

Theo D Palmer的其他文献

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{{ truncateString('Theo D Palmer', 18)}}的其他基金

Graduate Training in Stem Cell Biology and Regenerative Medicine
干细胞生物学和再生医学研究生培训
  • 批准号:
    9278892
  • 财政年份:
    2017
  • 资助金额:
    $ 27.48万
  • 项目类别:
Convergence of genetic and gestational immune mechanisms in 16p11.2-related ASD
16p11.2 相关 ASD 中遗传和妊娠免疫机制的趋同
  • 批准号:
    9009074
  • 财政年份:
    2016
  • 资助金额:
    $ 27.48万
  • 项目类别:
Convergence of genetic and gestational immune mechanisms in CHD8-related ASD
CHD8 相关 ASD 中遗传和妊娠免疫机制的融合
  • 批准号:
    9890858
  • 财政年份:
    2016
  • 资助金额:
    $ 27.48万
  • 项目类别:
Neuroimmune Signaling in Neural Transplantation
神经移植中的神经免疫信号传导
  • 批准号:
    8369326
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
Neuroimmune Signaling in Neural Transplantation
神经移植中的神经免疫信号传导
  • 批准号:
    8837922
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
GABRB3 and Placental Vulnerability in ASD
ASD 中的 GABRB3 和胎盘脆弱性
  • 批准号:
    8811472
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
GABRB3 and Placental Vulnerability in ASD
ASD 中的 GABRB3 和胎盘脆弱性
  • 批准号:
    8438258
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
Neuroimmune Signaling in Neural Transplantation
神经移植中的神经免疫信号传导
  • 批准号:
    8653851
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
Neuroimmune Signaling in Neural Transplantation
神经移植中的神经免疫信号传导
  • 批准号:
    8461539
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:
GABRB3 and Placental Vulnerability in ASD
ASD 中的 GABRB3 和胎盘脆弱性
  • 批准号:
    8619661
  • 财政年份:
    2012
  • 资助金额:
    $ 27.48万
  • 项目类别:

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    10590405
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NSF Postdoctoral Fellowship in Biology: Coalescent Modeling of Sex Chromosome Evolution with Gene Flow and Analysis of Sexed-versus-Gendered Effects in Human Admixture
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    2023
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用于识别癌症驱动因素的马赛克拷贝数改变的混合图谱
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Leveraging the Microbiome, Local Admixture, and Machine Learning to Optimize Anticoagulant Pharmacogenomics in Medically Underserved Patients
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