Collaborative Research:Excitatory Interneurons in the Mouse Locomotor Pattern Generator

这项提案将研究驱动脊椎动物运动的神经网络的进化。 要了解动物是如何运动的，有必要识别和研究控制运动的网络中的神经元。 一组参与鱼类和蝌蚪运动控制的兴奋性中间神经元的同源物现在已经在小鼠脊髓中被鉴定，基于它们的Chx10转录因子基因的表达。 这项提议将确定这些Chx10细胞的功能是否在哺乳动物中保守。使用钙敏感染料的光学成像将用于研究Chx10神经元在通过尾部刺激或对离体脊髓施加发射器诱发的运动活动期间的活性。 该合作提案的主要研究者已经产生了缺乏Chx10神经元的转基因小鼠，这些小鼠将用于研究这种损失对分离的脊髓运动活动的影响。 最后，将研究Chx10神经元的放电特性以及它们被血清素的调节，血清素有助于启动运动。 预计这些神经元对于正常运动是必不可少的，尽管在没有这些神经元的情况下仍然可能发生改变的运动（例如同步的奔马活动）。 血清素应该修改这些神经元，使它们为参与运动网络做好准备。 这个项目将帮助培养一名博士后和一名少数民族本科生，以研究产生简单节奏行为的神经网络的组织和功能。

This proposal will study the evolution of neural networks that drive locomotion in vertebrates. To understand how animals locomote, it is necessary to identify and study the neurons in the networks that control locomotion. Homologs of a set of excitatory interneurons that participate in locomotor control in fish and tadpoles have now been identified in the mouse spinal cord, based on their expression of the Chx10 transcription factor gene. This proposal will determine whether the function of these Chx10 cells has been conserved in mammals. Optical imaging using calcium-sensitive dyes will be used to study the activity of the Chx10 neurons during the locomotor activity evoked by tail stimulation or transmitter application to the isolated spinal cord. The principal investigator of the collaborative proposal has generated transgenic mice lacking the Chx10 neurons, which will be used to study the effects of this loss on locomotor activity in the isolated spinal cord. Finally, the firing properties of Chx10 neurons will be studied as well as their modulation by serotonin, which helps to initiate locomotion. It is expected that these neurons are essential for normal locomotion, though altered movements (such as synchronous galloping activity) may still occur in the absence of these neurons. Serotonin should modify these neurons to prepare them for participation in the locomotor network. This project will help train a postdoctoral fellow and a minority undergraduate to study the organization and function of neural networks that generate simple rhythmic behaviors.