Neuron-glia interactions in Drosphila visual neuropiles

果蝇视觉神经桩中神经元-胶质细胞的相互作用

• 批准号: 8444403
• 负责人: HONG-SHENG LI
• 金额: $ 39.07万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8444403
• 关键词: Amacrine Cells; Astrocytes; Biological; Biology; Cells; Defect; Drosophila eye; Drosophila genus; Epithelial; Eye; Feedback; Genetic; Genetic Models; Glutamates; Goals; Interneurons; Knowledge; Light; Maintenance; Mediating; Membrane; Molecular; Neurobiology; Neuroglia; Neurons; Neurotransmitter Receptor; Neurotransmitters; Phenocopy; Photoreceptors; Phototransduction; Proteins; Regulation; Research; Resolution; Retinal Diseases; Role; Signal Transduction; Speed; Structure; Synaptic Transmission; Testing; Therapeutic; Vision; Visual; Visual system structure; abstracting; base; design; fly; glutamate-gated chloride channel; knock-down; mutant; neuron development; novel; postsynaptic; prevent; response; retinal neuron

Abstract The long-term goal of the proposed research is to reveal functions and mechanisms of neuron-glia interaction in visual systems. As previous studies on vision have mostly been focused on the visual transduction cascades and the neuronal circuits, our knowledge about the role of glial cells in visual signaling is still very limited. Intriguingly, glial cells express receptors for neurotransmitters of visual interneurons in both mammalian and fly eyes. It is unknown whether glial cells directly communicate with those neurons for regulation of visual signaling. In our preliminary studies on Drosophila vision, we found that the visual epithelial glia may concentrate a glutamate-gated chloride channel GluCl in 'gnarl', a special glial membrane structure that typically interposes between a glutamatergic interneuron amacrine cell and its postsynaptic partner T1 cell. When the glutamate release from amacrine cell was blocked, the speed of photoreceptor repolarization at the end of light response reduced significantly. Importantly, this visual defect was phenocopied by knocking down the GluCl expression specifically in the epithelial glia, and was also observed in an ADAM protein mutant of impaired gnarl structure. Based on these observations, we propose the existence of a photoreceptor-amacrine cell-epithelial glia-photoreceptor feedback loop, which functions to reinforce the speed of photoreceptor repolarization and is thus important for the temporal resolution of vision. Using a combination of molecular and cell biological, genetic, histological, and electrophysiological approaches, we propose to further investigate this novel function of visual epithelial glia. Specifically, we will 1. Test the hypothesis that laminar epithelial glia receive neuronal input through the glutamate-gated chloride channel GluCl; 2. Test the hypothesis that an ADAM protein MMD is required to localize GluCl in the gnarl structure for the neuron-glia signaling; 3. Identify the mechanism of epithelial glia-mediated photoreceptor regulation. These studies are not only important to visual biology, but will also contribute to our understanding of glial function in general.

摘要 本研究的长期目标是揭示神经胶质细胞的功能和机制 视觉系统中的交互。由于以往对视觉的研究大多集中在视觉上， 转导级联和神经元回路，我们的知识的作用，胶质细胞在视觉 信令仍然非常有限。有趣的是，神经胶质细胞表达视觉神经递质的受体， 在哺乳动物和苍蝇的眼睛中间神经元。目前尚不清楚神经胶质细胞是否直接与 控制视觉信号的神经元。在我们对果蝇视觉的初步研究中， 视觉上皮神经胶质细胞可以将谷氨酸门控氯离子通道GluCl集中在“gnarl”中， 一种胶质细胞膜结构，典型地介于神经元能的中间神经元无长突细胞和其 突触后伴侣T1细胞。当无长突细胞释放谷氨酸被阻断时， 光反应结束时感光细胞复极化明显降低。重要的是，这种视觉 通过特异性敲低上皮胶质细胞中的GluCl表达来表型复制缺陷， 也在受损的Gnarl结构的ADAM蛋白突变体中观察到。根据这些观察，我们 提出存在光感受器-无长突细胞-上皮胶质细胞-光感受器反馈回路， 其功能是增强感光细胞复极的速度，因此对于暂时的 视觉的分辨率。利用分子和细胞生物学、遗传学、组织学和 电生理方法，我们建议进一步研究这种新的功能，视觉上皮细胞 神经胶质。具体来说，我们将 1.测试层状上皮胶质细胞通过谷氨酸门控的 氯离子通道GluCl; 2.检验如下假设：需要ADAM蛋白MMD将GluCl定位在Gnarl结构中， 神经元-胶质细胞信号转导; 3.确定上皮胶质细胞介导的感光细胞调节机制。 这些研究不仅对视觉生物学具有重要意义，而且将有助于我们对神经胶质细胞的理解。 功能一般。