Mechanisms of Calcium Transients in Neuronal Development

神经元发育中钙瞬变的机制

• 批准号: 7232348
• 负责人: NICHOLAS CANADAY SPITZER
• 金额: $ 30.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7232348
• 关键词: Xenopus; action potentials; axon; calcium channel; calcium flux; cell differentiation; developmental genetics; developmental neurobiology; gene expression; growth cones; mechanoreceptors; membrane potentials; neurogenesis; neurotransmitter transport; reporter genes; sodium potassium exchanging ATPase; spinal cord; tissue /cell culture

DESCRIPTION (provided by applicant): In previous work we discovered three classes of spontaneous transient elevations of intracellular calcium (Ca) in embryonic Xenopus spinal neurons and showed that they have distinct functions, regulating aspects of differentiation in a frequency-dependent manner prior to synapse formation: 1) Ca spikes are generated by developmental transient Ca-dependent action potentials and regulate expression of neurotransmitters. 2) Growth cone Ca transients are generated locally in the growth cone and regulate the rate of axon extension. 3) Filopodial Ca transients are produced at the tips of filopodia and regulate growth cone turning. The proposed research has three specific aims that address the mechanisms of action of Ca transients in differentiation of these embryonic spinal neurons. The first aim investigates the mechanisms by which Ca spikes regulate neurotransmitter expression. The second aim analyzes the mechanism generating changes in membrane potential that lead to onset and termination of Ca spiking. The third aim investigates the mechanism by which voltage-gated Ca channels regulate growth cone function. We describe experiments to address the following questions: What molecules are involved in the action of Ca spikes? What mechanisms generate the changes in membrane potential that lead to onset and termination of the period of Ca spiking? Does the mechanism of action of growth cone voltage-gated Ca channels involve interaction with extracellular matrix molecules or mechanically enhanced transmitter release? The immediate goal of this research is to test hypotheses about the mechanisms of Ca transients in the early stages of differentiation of vertebrate spinal neurons. The long term goal is to provide information about the cellular and molecular machinery that governs processes of development, which will contribute to understanding developmental disorders of the nervous system.

描述（由申请人提供）：在之前的工作中，我们发现了胚胎非洲爪蟾脊髓神经元中细胞内钙（Ca）的三类自发瞬时升高，并表明它们具有不同的功能，在突触之前以频率依赖的方式调节分化的各个方面形成：1) Ca 尖峰由发育瞬时 Ca 依赖性动作电位产生并调节神经递质的表达。 2) 生长锥 Ca瞬变在生长锥中局部产生并调节轴突延伸的速率。 3)丝状伪足尖端产生丝状伪足Ca瞬变并调节生长锥转动。拟议的研究有三个具体目标，旨在解决 Ca 瞬变在这些胚胎脊髓神经元分化中的作用机制。第一个目标是研究 Ca 尖峰调节神经递质表达的机制。第二个目标是分析导致 Ca 尖峰发生和终止的膜电位变化的机制。第三个目标是研究电压门控 Ca 通道调节生长锥功能的机制。我们描述实验来解决以下问题：哪些分子参与 Ca 尖峰的作用？哪些机制会产生膜电位的变化，从而导致 Ca 尖峰时期的开始和终止？生长锥电压门控 Ca 通道的作用机制是否涉及与细胞外基质分子的相互作用或机械增强的递质释放？这项研究的直接目标是检验有关脊椎动物脊髓神经元分化早期阶段 Ca 瞬变机制的假设。长期目标是提供有关控制发育过程的细胞和分子机制的信息，这将有助于理解神经系统的发育障碍。