Investigation of CNS synaptogenesis

在神经元发育过程中，神经元延伸其突起以支配特定的靶点。神经元之间的连接（称为突触）的形成对于建立神经系统的结构至关重要。突触的产生也被认为是学习和记忆发生的机制之一。最近，在神经系统中，在识别负责将轴突引导到其适当靶点的分子方面取得了重大进展，但参与这些接触部位分化为功能性突触的分子仍然未知。Netrin是一个蛋白质家族，几乎专门研究其作为迁移轴突的指导线索的作用。我们最近发现，netrin-1在出生后继续存在于神经系统中，并在突触处富集。这些观察使我们研究netrin-1及其受体在调节新突触形成和维持中的新功能。我们已经表明，netrin-1刺激导致突触密度增加。这些研究旨在确定netrin-1及其受体对突触形成、重塑和维持的贡献。 我们的初步研究结果表明，我们已经确定了一种新的机制，在神经元发育过程中发挥重要作用，调节突触发生，并可能有助于突触修饰在成人大脑。 研究这一点将有助于提高我们对调节神经元之间通讯机制的基本理解。 更好地了解正常的大脑功能将有可能提高我们再生和重新连接在神经退行性疾病或创伤性损伤后失去的神经元连接的能力。

During neuronal development, neuron extends their processes to innervate specific targets. The formation of connections between neurons (called synapses) is essential to establish the architecture of the nervous system. The creation of synapses is also thought to be one of the mechanisms by which learning and memory occur. Recently, in the nervous system, significant progress has been made in identifying molecules responsible for guiding axons to their appropriated target, but the molecules involved in the differentiation of these sites of contact into functional synapses still unknown. Netrins are a family of proteins that have been studied almost exclusively for their role as guidance cues for migrating axons. We recently showed that netrin-1 continues to be present in the nervous system after birth and are enriched at the synapse. These observations led us to investigate a novel function for netrin-1 and its receptors in regulating the formation and the maintenance of new synapses. We have shown that netrin-1 stimulation causes an increase in synapse density. The proposed studies aim to identify the contribution of netrin-1 and its receptors to the formation, remodeling, and maintenance of synapse. Our preliminary findings suggest that we have identified a novel mechanism that plays and important role regulating synaptogenesis during neuronal development and may contribute to synaptic modification in the adult brain. Studying this will contribute to improve our basic understanding of mechanisms that regulate communication between neurons. A better understanding of normal brain functioning will potentially improve our ability to regenerate and reconnect neuron connections lost during neurodegenerative diseases or after traumatic injuries.