CAREER: Genetic Analysis of NMDA Receptor Expression

这项由NSF教师早期职业发展（CAREER）奖支持的研究考察了神经元多样性的分子基础。神经系统包含大量的专门神经元，它们在称为突触的不同接触点上相互交流。突触功能是学习和记忆的基础，突触功能障碍是许多神经系统疾病的基础。随着神经元的发育，它必须表达突触通讯所需的分子。在这些分子中，有神经递质受体，它们接收在突触处传递的信号。一类重要的神经递质受体是那些与神经递质谷氨酸结合的受体。如果这些受体表达不当，神经系统的功能就会被破坏。NSF基金会支持的实验将确定谷氨酸受体NMDA亚型表达所需的基因。利用分子生物学和遗传学工具的实验策略将被用来发现在简单的模式生物秀丽隐杆线虫中调节这些受体表达的基因。NMDA受体被认为参与简单形式的联想学习，在许多神经系统疾病中也起着重要作用，该建议将研究纳入神经元功能的基本机制，并在科学探究的实践和理论方面对大学生进行早期培训。这些研究将提供一个详细的分子基础上的理解所需的基因产物的表达，组装和定位的NMDA受体在C。优雅该策略利用了强大的遗传技术，使快速识别的基因产物在这个模式生物。几乎所有突触功能所需的基因产物在简单生物和人类之间都是保守的。因此，本研究的结果可应用于人类神经系统的研究。

The research supported by this NSF Faculty Early Career Development (CAREER) award examines the molecular basis of neuronal diversity. The nervous system contains tremendous numbers of specialized neurons that communicate with one another at distinct points of contact called synapses. Synaptic function underlies learning and memory and dysfunction of the synapse underlies many neurological disorders. As a neuron develops, it must express the molecules needed for synaptic communication. Amongst these molecules are the neurotransmitter receptors that receive the signal transmitted at the synapse. One important class of neurotransmitter receptors are those that bind to the neurotransmitter glutamate. If these receptors are improperly expressed, the function of the nervous system is disrupted.The experiments supported by this NSF award will identify genes required for the expression of the NMDA subtypes of glutamate receptors. An experimental strategy that utilizes the tools of molecular biology and genetics will be used to discover genes that regulate the expression of these receptors in the simple model organism Caenorhabditis elegans. The NMDA receptors are most recognized as being involved in simple forms of associative learning and also play important roles in many neurological disorders.This proposal integrates research into the fundamental mechanisms of neuronal function with the early training of undergraduates in the practice and theory of scientific inquiry. The studies will provide a detailed molecular-based understanding of the gene products required for the expression, assembly and localization of NMDA receptors in C. elegans. The strategy takes advantage of the powerful genetic techniques that enable rapid identification of gene products in this model organism. Almost all gene products required for synaptic function are conserved between simple organisms and humans. Therefore, the results of this research can be applicable to the study of the human nervous system.