Synaptic transmission at retinal ribbon synapses

在眼睛和内耳的感觉细胞中，神经递质谷氨酸以分级的方式在活动区释放。 连续的方式。这些细胞已经进化出称为突触带的特殊结构。这些 蛋白质结构将突触囊泡拴在活性区附近。根据它们的位置， 栓系囊泡和感觉神经元的特性，这些细胞器有很长的 被认为是重要的，以维持谷氨酸盐的持续释放。其他几个功能 也被归因于丝带。然而，最近的证据对这些想法提出了质疑。该补助金的重点是 为了了解突触带在感觉突触传递中的作用，使用缺乏神经传导的动物模型， Ribeye是一种蛋白质，在丝带中含量最丰富，在其他任何地方都找不到。没有Ribeye 导致膜相关突触带的损失，而不损失其他突触前蛋白。具体目标1 研究如何Ribeye去除和突触带的损失影响神经递质释放， 光感受器具体目标2着眼于来自相同动物的双极细胞中突触释放的特性。 在特定目标3中，我们将对缺乏Ribeye的细胞中的单个突触囊泡进行成像，以测量囊泡的比率。 移动和补充，以测试色带在这些过程中的作用。了解功能区功能 可能会提供线索，帮助了解专门影响视力和听力的疾病。此外该 对这些特化神经元中突触前过程的基本理解将具有更广泛的意义 对于一般的神经元通讯，因此可能有助于我们对神经元通讯各个方面的理解 精神健康和神经系统疾病。

In sensory cells of the eye and inner ear the neurotransmitter glutamate is released at active zones in a graded and continuous manner. These cells have evolved specialized structures known as synaptic ribbons. These proteinaceous structures tether synaptic vesicles near active zones. Based on their location, abundance of tethered vesicles, and properties of the sensory neurons in which they are found, these organelles have long been thought to be important for maintaining the continuous release of glutamate. Several other functions have also been ascribed to ribbons. However, recent evidence casts doubt on these ideas. The focus of this grant is to understand the role of synaptic ribbons in sensory synaptic transmission using animal models that lack Ribeye, a protein that is both the most abundant within the ribbon and not found anywhere else. Lack of Ribeye leads to loss of membrane associated synaptic ribbons, without loss of other presynaptic proteins. Specific Aim 1 investigates how Ribeye removal and loss of synaptic ribbons affects neurotransmitter release from photoreceptors. Specific Aim 2 looks at the properties of synaptic release in bipolar cells from the same animals. In Specific Aim 3, we will image single synaptic vesicles in cells lacking Ribeye to measure rates of vesicle movement and replenishment to test the role of the ribbon in these processes. 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.