Rab3A-Mediated Regulation of Quantal Size after Loss of Activity

项目4 每年有近10万人因创伤性脑或脊髓损伤而永久残疾。 今天，有500多万永久性残疾人士在世。神经科学研究的一个主要目标是 了解并促进神经系统损伤后恢复的机制。备用神经元反应 对伤害不利的，或试图对伤害进行补偿。不幸的是，即使是恢复机制也可以 产生意想不到的后果，如脊髓损伤后痉挛，或皮质损伤后癫痫 脑部受伤。这些异常行为是由于单个神经元功能的改变。突触 传输，即信号从一个神经元到下一个神经元的交流，异常增加或 减少了。损伤后突触传递的改变可能通过正常的机制发生。 学习一项新任务或习得一门外语的可塑性。或者，它们可能涉及 完全独特的机制。我们的目标是确定损伤诱导可塑性的细胞机制。 突触传递的信号。在脊髓或大脑的复杂环境中，这是一项艰巨的任务， 在那里，数千个神经元彼此之间制造数百万个突触。我们通过观察来简化这个问题 在损伤对一个突触的影响，运动神经元和肌肉之间的突触， 神经肌肉接头。为了模拟损伤的影响，我们用以下物质阻断神经肌肉接头的所有活动 河豚毒素，河豚鱼的一种毒素，可以通过麻痹横隔膜而致死。我们的数据表明 突触囊泡蛋白RabSA对损伤诱导的可塑性是必不可少的。为了检验这一假设，我们将 确定在RabSA功能受损的突变小鼠中，损伤诱导的可塑性是如何改变的。这个 这项建议的研究将大大促进我们对神经系统对Long的反应的理解 受伤后活动的长期变化。这些知识对于防止长期的 残疾人士。

Project 4 Every year almost 100,000 people suffer permanent disability from a traumatic brain or spinal cord injury. Over 5 million people with permanent disability are alive today. A major goal of neuroscience research is to understand and promote mechanisms that allow recovery after nervous system injury. Spared neurons react adversely to the injury, or try to compensate for the injury. Unfortunately, even recovery mechanisms can produce unintended consequences, such as spasticity after spinal cord injury, or epilepsy after a cortical brain injury. These anomalous behaviors are due to changes in the functions of individual neurons. Synaptic transmission, the communication of a signal from one neuron to the next, is abnormally increased or decreased. The changes in synaptic transmission after injury may occur through mechanisms of normal plasticity that underlie learning a new task or acquiring a foreign language. Alternatively, they may involve completely unique mechanisms. Our goal is to determine the cellular mechanisms of injury-induced plasticity of synaptic transmission. This is a Herculean task in the complex environment of the spinal cord or brain, where thousands of neurons make millions of synapses with each other. We simplify the problem by looking at the effects of injury on one synapse, the synapse between the motor neuron and the muscle, the neuromuscular junction. To mimic the effects of injury, we block all activity at the neuromuscular junction with tetrodotoxin, the toxin of puffer fish that can kill a person by paralyzing the diaphragm. Our data suggest that the synaptic vesicle protein RabSA is essential for injury-induced plasticity. To test this hypothesis, we will determine how injury-induced plasticity is altered in a mutant mouse with impaired RabSA function. The studies in this proposal will significantly advance our understanding of the nervous system's response to long term changes in activity that occur after injury. Such knowledge is essential in the fight to prevent long term disabilities.