Role of calcium signaling in axon-dendrite interactions during synapse development

突触发育过程中钙信号在轴突-树突相互作用中的作用

• 批准号: 43761670
• 负责人: Dr. Christian Lohmann
• 金额: --
• 依托单位: Netherlands Institute of Neuroscience
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/43761670?language=en
• 关键词: Role; calcium; signaling; axon; dendrite

During the development of the nervous system, axons and dendrites establish contacts some of which will be stabilized and mature into synapses, whereas others will be eliminated. Very little is known about the turnover rate of such contacts. Moreover, while it is clear that patterns of neuronal activity shape synaptic connectivity, the specific activity patterns or signaling factors, which determine the fate of a given contact, have not been identified. Dendritic filopodia are neuronal processes that facilitate contact formation with axons. Recently, we were able to show that the growth of filopodia is characteristically correlated with and regulated by dendritic calcium signaling. Now, we have developed new strategies to image axonal and dendritic structure and calcium signaling simultaneously in hippocampal slices from developing rats or mice. We propose experiments, which take advantage of these technical advances to investigate the structural and functional interactions between dendrites and axons that precede synapse formation. We will describe how axons and dendrites initiate contact and determine the turnover rates of contacts. Subsequently, we will investigate whether calcium transients are generated when dendrites and axons form contacts and finally we will determine whether specific patterns of calcium signaling regulate the establishment, maturation, or elimination of synaptogenic contacts. These experiments will help to understand better, how neurons select synaptic partners and establish specific neuronal networks, which underlie the functions of the brain.

在神经系统的发育过程中，轴突和树突建立了一些联系，其中一些将稳定并成熟为突触，而另一些将被消除。人们对这类接触的周转率知之甚少。此外，虽然神经元活动模式塑造突触连通性是很清楚的，但决定特定接触命运的特定活动模式或信号传导因素尚未被确定。树突丝状足是促进与轴突形成接触的神经元突起。最近，我们能够证明丝状足的生长特征性地与树突钙信号相关并受其调节。现在，我们已经开发了新的策略，同时在发育中的大鼠或小鼠的海马切片中成像轴突和树突结构以及钙信号。我们提出实验，利用这些技术进步来研究突触形成之前树突和轴突之间的结构和功能相互作用。我们将描述轴突和树突如何启动接触并确定接触的周转率。随后，我们将研究当树突和轴突形成接触时是否会产生钙瞬变，最后我们将确定钙信号的特定模式是否调节突触性接触的建立、成熟或消除。这些实验将有助于更好地理解神经元如何选择突触伙伴并建立特定的神经元网络，这是大脑功能的基础。