Mechanisms of Calcium Transients in Neuronal Development

神经元发育中钙瞬变的机制

• 批准号: 7098164
• 负责人: NICHOLAS CANADAY SPITZER
• 金额: $ 4.25万
• 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/7098164
• 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）：在先前的工作中，我们发现了三类的自发性短暂升高（CA）在胚胎爪蟾脊髓神经元中的细胞内钙（CA）的升高，表明它们具有不同的功能，以频率依赖性形成的频率依赖性方式调节差异化的方面：1）CA SPIKES的依赖性CARINDER依赖性依赖性依赖性依赖性依赖性依赖性依赖性依赖性。 2）生长锥瞬变是在生长锥中局部生成的，并调节轴突延伸的速率。 3）丝状Ca瞬变是在丝状尖端产生的，并调节生长锥转弯。拟议的研究具有三个特定的目的，可以解决CA瞬态在分化这些胚胎脊柱神经元的作用机理。第一个目标研究了CA尖峰调节神经递质表达的机制。第二个目标分析了产生膜电位变化的机制，从而导致CA尖峰的发作和终止。第三个目标研究了电压门控CA通道调节生长锥功能的机制。我们描述了解决以下问题的实验：CA尖峰的作用涉及哪些分子？哪些机制会产生膜电位的变化，从而导致CA尖峰时期的发作和终止？生长锥电门控CA通道的作用机理是否涉及与细胞外基质分子的相互作用或机械增强的发射器释放？这项研究的直接目的是检验有关脊椎动物脊柱神经元分化早期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。