Maintenance and Plasticity at the Frog Neuromuscular Junction

IBN 9602136 PI：伊丽莎白·A·康纳神经元在称为突触的特殊接触点与它们的目标细胞通信。为了确保这些细胞之间的可靠通信和神经系统的正常功能，神经元和其靶细胞之间的突触的协调维持是必要的。虽然神经元和它们的目标之间的一些突触贯穿动物的整个生命，但神经元维持在突触位置的机制尚不清楚。这项建议的目标是以青蛙神经肌肉接头为模型，确定影响突触神经元稳定性的因素。在青蛙神经肌肉交界处，运动神经元与目标肌肉细胞形成突触。青蛙神经肌肉接头是一个研究突触稳定性的强大系统，因为神经元可以在没有靶肌肉的情况下进行研究，以揭示通常在靶肌肉存在的情况下掩盖的非肌肉稳定相互作用。此外，可以操纵目标剥夺神经元的稳定性来测试稳定因素。神经胶质支持细胞，即终末雪旺细胞，在神经元的稳定和维持中的作用，将通过评估终末雪旺细胞从已确定的突触位置移除后神经元的稳定性来确定。将测试雪旺细胞产生的一种神经营养因子拯救和稳定神经元的能力。在突触位置或附近发现的结缔组织分子在神经元稳定中的作用也将被确定。这些实验将为稳定和维持突触部位神经元的机制提供新的信息，并将扩大我们对支配突触可塑性的分子和细胞相互作用的理解。

IBN 9602136 PI: Elizabeth A. Connor Neurons communicate with their target cells at specialized points of contact called synapses. The coordinated maintenance of the synapse between a neuron and its target is necessary to ensure reliable communication between these cells and the normal functioning of the nervous system. Though some synapses between neurons and their targets persist throughout the entire life of an animal, the mechanism by which neurons are maintained at synaptic sites is not understood. The goal of this proposal is to identify factors that contribute to the stability of neurons at synapses using the frog neuromuscular junction as a model. At the frog neuromuscular junction, a motor neuron forms a synapse with a target muscle cell. The frog neuromuscular junction is a powerful system in which to study synapse stability since neurons can be studied in the absence of target muscle to reveal nonmuscle stabilization interactions normally masked in the presence of target. Further, the stability of target-deprived neurons can be manipulated to test for stabilization factors. The role of a glial support cell, the terminal Schwann cell, in the stability and maintenance of the neuron will be determined by assessing the stability of neurons after removal of terminal Schwann cells from identified synaptic sites. The ability of a neurotrophic factor produced by Schwann cells to rescue and stabilize neurons will be tested. The role of connective tissue molecules found at or near synaptic sites in the stabilization of neurons will also be determined. These experiments will yield new information on the mechanisms that stabilize and maintain neurons at synaptic sites and will expand our understanding of the molecular and cellular interactions that govern synaptic plasticity.