Retinal Synaptic Transmission

描述（由申请人提供）：在眼睛和内耳的感觉神经元中，神经递质谷氨酸在活跃区以分级和连续的方式释放。在这些神经元中进化出了称为突触带的特殊结构。突触带是一种亲锇的蛋白质结构，它将突触囊泡系在活性区附近。由于它们的形态、在细胞内的位置和发现它们的细胞类型，这些细胞器对谷氨酸的持续释放无疑是重要的；然而，丝带如何帮助完成这项任务尚不清楚。这项资助的重点是研究突触带在感觉突触传递中的作用，长期目标是解决从这些重要细胞释放神经递质所涉及的事件的时间序列。特异性目的1是观察囊泡是如何附着在突触带和远离突触带的质膜上的。特异性目标2将探讨突触释放的特性。特异性目的3探讨突触带的可塑性。了解色带的功能可能会提供一些线索，帮助我们了解那些特别影响视力和听力的疾病。此外，对这些特殊神经元突触前过程的基本理解将对一般的神经元交流产生更广泛的影响，因此，可能有助于我们对精神健康和神经系统疾病的各个方面的理解。公共卫生相关性：神经系统中的信息在突触的神经细胞之间传递，在“突触前”神经细胞中的电脉冲导致神经递质从称为突触囊泡的小膜结合结构中释放出来。在眼睛和内耳的感觉神经元中，神经递质谷氨酸从突触囊泡中以分级和连续的方式释放，这一过程中的缺陷可能是遗传性失明和耳聋的基础。这个建议研究神经递质的强直性释放从一个这样的特殊神经元在视网膜。

DESCRIPTION (provided by applicant): In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released at active zones in a graded and continuous manner. In these neurons specialized structures have evolved, known as synaptic ribbons. Synaptic ribbons are osmiophilic proteinaceous structures that tether synaptic vesicles near active zones. Because of their morphology, location within the cells and the cell types where they are found, these organelles are undoubtedly important for the continuous release of glutamate; how ribbons aid in this task, however, remains unclear. The focus of this grant is to study the role of synaptic ribbons in sensory synaptic transmission, with the long term goal to resolve the temporal sequence of events that are involved in the release of neurotransmitter from these important cells. Specific Aim 1 is to look at how vesicles attach to the ribbon and to plasma membrane at sites away from the synaptic ribbon. Specific Aim 2 will look at the properties of synaptic release. Specific Aim 3 explores the plasticity of the synaptic ribbons. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders. PUBLIC HEALTH RELEVANCE: Information in the nervous system is transmitted between nerve cells at the synapse, where an electrical impulse in the "presynaptic" nerve cell causes the release of neurotransmitter from small membrane bound structures, known as synaptic vesicles. In sensory neurons of the eye and inner ear the neurotransmitter, glutamate, is released from synaptic vesicles in a graded and continuous manner and deficiencies in this process may underlie hereditary forms of blindness and deafness. This proposal studies the tonic release of neurotransmitter from one such specialized neuron in the retina.