The role of Wnt signalling in synaptic maintenance

功能性突触的形成是两个神经细胞(神经元)之间的接触点，对正常的大脑功能至关重要。突触是非常动态的结构，在有机体的整个生命过程中都会生长、缩小和改变形状。突触前神经元(神经递质释放细胞)和突触后靶细胞(神经递质反应细胞)之间的对话对于突触的形成、生长和维持是必不可少的。重要的是，新突触的形成和旧突触的重塑是学习和记忆等重要功能的基础。此外，最近的研究表明，在几种神经退行性疾病中观察到的神经元死亡之前，突触丢失。然而，关于突触是如何维持或免受损伤的知之甚少。我们的实验室一直在研究称为Wnts的分泌因子在突触维持中的作用。我们发现，WNT阻断导致成熟突触的丢失，这表明WNT对它们的维持至关重要。在这项拨款提案中，我们将研究WNTS调节突触维持的分子机制，以及这一过程如何影响神经元连接和动物行为。我们的结果可能有助于开发治疗突触受损的疾病的治疗策略。

The formation of functional synapses, points of contact between two nerve cells (neurons) is crucial for proper brain function. Synapses are very dynamic structures that grow, shrink and change shape through the entire life of the organism. A dialogue between the pre-synaptic neuron (neurotransmitter releasing cell) and its postsynaptic target (a neurotransmitter responding cell) is essential for the formation, growth and maintenance of synapses. Importantly, the formation of new synapses and the remodelling of old ones underlay important functions such as learning and memory. Moreover, recent studies suggest that synaptic loss precedes the death of neurons observed in several neurodegenerative diseases. However, little is known about how synapses are maintained or protected against injury.Our laboratory has been studying the function of secreted factors, called Wnts, in the maintenance of synapses. We found that Wnt blockade induces the loss of mature synapses indicating that Wnts are critical for their maintenance. In this grant proposal, we will examine the molecular mechanism by which Wnts regulate synaptic maintenance and how this process influences neuronal connectivity and animal behaviour. Our results could contribute to the development of therapeutic strategies for the treatment of diseases in which synapses are compromised.