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

在神经系统的发育过程中，轴突和树突建立联系，其中一些将被稳定并成熟为突触，而另一些将被消除。对这种联系人的更替率知之甚少。此外，虽然神经元活动的模式塑造了突触连接，但决定给定接触命运的特定活动模式或信号传导因子尚未确定。树突丝状伪足是促进与轴突接触形成的神经元过程。最近，我们能够表明，丝状伪足的生长特征与树突状钙信号相关并受其调节。现在，我们已经开发出新的策略，在发育中的大鼠或小鼠的海马切片中同时成像轴突和树突结构和钙信号。我们提出的实验，利用这些技术的进步，研究突触形成之前的树突和轴突之间的结构和功能的相互作用。我们将描述如何轴突和树突发起接触，并确定营业额的接触。随后，我们将研究是否产生钙瞬变时，树突和轴突形成接触，最后，我们将确定是否特定的钙信号模式调节突触接触的建立，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。

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.