Role of P2X and P2Y ATP Receptors in Neuromuscular Development

0077634HumeNerve细胞通过被称为突触的狭窄接触区域相互传递信息。进入的突触前细胞释放一种化学信号（神经递质），它与目标细胞上的受体结合，引起电兴奋或抑制。这些实验的总体目标是了解使发育中的突触达到稳定、成熟状态的机制。要探讨的主要假设是，除了已知的在神经和肌肉之间传递促进突触成熟的两个信号（agrin和ARIA）外，还有一个额外的信号系统也传递关键信息。该信号系统由突触前末端释放的ATP（5'三磷酸腺苷）与肌肉细胞表面两种不同类型的ATP受体相互作用组成。这一假设将通过使用分子生物学和药理学工具来测试，以改变鸡蛋内发育的鸡肌肉细胞表面和细胞培养中at受体的功能。重要的是成熟的神经肌肉突触是稳定的，这样它们才能可靠地控制神经系统的日常活动，比如命令肌肉以允许我们呼吸的模式运动。然而，了解促进突触生长和成熟的机制也可能使我们深入了解在成熟神经系统中突触并不总是稳定的其他区域突触功能变化的机制。突触反应振幅的变化被认为是学习和遗忘发生的细胞基础。

0077634HumeNerve cells communicate information to each other at narrow zones of contactreferred to as synapses. The incoming presynaptic cell releases a chemicalsignal (the neurotransmitter), which binds to receptors on the target cell,eliciting electrical excitation or inhibition. The general goal of theseexperiments is to understand the mechanisms that allow developing synapsesto reach their stable, mature state. The principal hypothesis to be exploredis that in addition to the two signals known to pass between nerve andmuscle to promote synapse maturation (agrin and ARIA), an additionalsignaling system also transmits key information. This proposed signalingsystem consists of ATP (adenosine 5' triphosphate) released from presynapticterminals interacting with two different types of ATP receptors on themuscle cell surface. The hypothesis will be tested by using molecularbiological and pharmacological tools to alter the function of the ATPreceptors on the surface of chick muscle cells developing within the egg,and in cell culture.It is important that mature neuromuscular synapses be stable, so that theycan reliably control of the routine actions of the nervous system such ascommanding muscles to move in the pattern that allows us to breathe.However, understanding the mechanisms that promote synaptic growth andmaturation are likely to also provide us with insight into the mechanismsthat bring about changes in synaptic function in other regions of the maturenervous system where synapses are not always stable. Changes in theamplitude of synaptic responses are thought to be the cellular basis bywhich learning and forgetting occur.