Retinal Synaptic Transmission

描述(申请人提供)：在眼睛和内耳的感觉神经元中，神经递质谷氨酸以分级和连续的方式在活动区释放。在这些神经元中，进化出了特殊的结构，称为突触带。突触带是连接活动区附近突触小泡的嗜嗅性蛋白质结构。由于它们的形态、在细胞内的位置以及它们被发现的细胞类型，这些细胞器对于谷氨酸的持续释放无疑是重要的；然而，这些细胞器如何帮助完成这一任务仍不清楚。这项拨款的重点是研究突触带在感觉突触传递中的作用，长期目标是解决与这些重要细胞释放神经递质有关的事件的时间序列。具体目标1是观察囊泡如何附着在突触带和远离突触带的部位的质膜上。《特定目标2》将研究突触释放的特性。具体目标3探索突触带的可塑性。了解功能区的功能可能会为了解特定影响视力和听力的疾病提供线索。此外，对这些特殊神经元突触前过程的基本了解将对神经元的总体交流产生更广泛的影响，从而可能有助于我们对心理健康和神经疾病的各个方面的理解。与公共卫生相关：神经系统中的信息在突触的神经细胞之间传输，在突触前神经细胞中的电脉冲导致神经递质从被膜结合的小结构释放，称为突触小泡。在眼睛和内耳的感觉神经元中，神经递质谷氨酸以分级和连续的方式从突触小泡中释放出来，这一过程中的缺陷可能是遗传性失明和耳聋的基础。这项建议研究视网膜中一种特殊神经元的神经递质的紧张性释放。

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.