Collaborative Research: Calcium Entry and Transmitter Release at the Frog NMJ

神经系统中的细胞通过称为突触的特殊区域进行交流。当神经放电时，钙离子从周围的细胞外液进入突触，导致神经递质分子被释放到通讯细胞之间的突触间隙中。然而，从钙进入到递质释放的分子事件的顺序仍然未知。为了更好地理解这一重要过程，这项研究将结合实验室实验和大规模计算机模拟，建立详细的三维模型，研究青蛙神经和肌肉细胞之间的突触中钙触发的神经递质释放。在许多方面，青蛙的突触与许多哺乳动物（包括人类）的突触非常相似，但它为实验室和计算研究的结合提供了独特的机会。这使得它成为创建高度逼真和准确的模型的理想选择。利用这些模型，假设将被开发和测试，以解释突触如何使用钙来触发神经递质释放，以及反复的神经放电如何改变释放，正如所有突触在对变化的行为条件做出反应时发生的那样。现实的三维计算机模型的发展也为转型培训和教育提供了独特的机会。本科生、研究生和博士后学员将直接参与这些研究，模型的高质量动画将被改编用于课堂。该项目的共同负责人（匹兹堡大学的S. Meriney和卡耐基梅隆大学的J. Stiles）及其同事将在匹兹堡大学、匹兹堡超级计算中心和卡耐基梅隆大学的本科生和研究生神经科学、生物学和计算生物学课程、多机构暑期学院（www.ccbb.pitt.edu/bbsi）、研讨会和基于网络的教程（www.mcell.psc.edu/tutorials/tlist.htm）中使用新的教材。新的教材也将出现在CMIST项目中，这是一个由Stiles博士指导的国家生物医学超级计算资源的本科和K-12外展项目（www.nrbsc.org/cmist）。

Cells in the nervous system communicate at specialized regions called synapses. When a nerve fires, calcium ions enter synapses from the surrounding extracellular fluid and cause neurotransmitter molecules to be released into the synaptic cleft between the communicating cells. However, the sequence of molecular events leading from calcium entry to transmitter release remains unknown. To better understand this important process, this research will combine laboratory experiments and large-scale computer simulations to build detailed 3-D models of calcium-triggered neurotransmitter release at the synapse between a nerve and muscle cell in the frog. In many respects, the frog synapse is quite similar to many mammalian synapses (including human), and yet it presents unique opportunities for combined laboratory and computational studies. This makes it an ideal choice for creation of highly realistic and accurate models. Using these models, hypotheses will be developed and tested to explain how synapses use calcium to trigger neurotransmitter release, and how repeated nerve firing changes release, as occurs at all synapses as they respond to changing behavioral conditions. Development of realistic 3-D computer models also presents unique opportunities for transformational training and education. Undergraduate, graduate, and postdoctoral trainees will participate directly in these studies, and high quality animations of the models will be adapted for use in the classroom. The project co-directors (S. Meriney, Univ. of Pittsburgh, and J. Stiles, Carnegie Mellon Univ.) and faculty colleagues will use the new teaching material at the University of Pittsburgh, the Pittsburgh Supercomputing Center, and Carnegie Mellon University, in undergraduate and graduate Neuroscience, Biology, and Computational Biology courses, a multi-institutional summer institute (www.ccbb.pitt.edu/bbsi), workshops, and web-based tutorials (www.mcell.psc.edu/tutorials/tlist.htm). New teaching material will also be featured in the CMIST program, an undergraduate and K-12 outreach program at the National Resource for Biomedical Supercomputing, directed by Dr. Stiles (www.nrbsc.org/cmist).