Cross-talk between ganglion-cell photoreceptors and other neurons in the retina

神经节细胞感光器和视网膜其他神经元之间的串扰

• 批准号: 8053770
• 负责人: KWOON Y. WONG
• 金额: $ 23.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8053770
• 关键词: Address; Agonist; Amacrine Cells; Animal Model; Behavior; Behavioral; Biological Clocks; Brain; Cell Nucleus; Cells; Chemicals; Conscious; Data; Data Quality; Development; Docking; Dopamine; Dyes; Environment; Eye; Failure; Functional disorder; Ganglia; Goals; Grant; Health; Human; Image; Investigation; Jet Lag Syndrome; Knowledge; Light; Lighting; Malignant Neoplasms; Mammals; Measures; Mediating; Mental Depression; Methods; Morphology; Mus; Neuromodulator; Neuromodulator Receptors; Neurons; Organism; Output; Paper; Phase; Photoreceptors; Phototherapy; Physiological; Physiology; Policies; Process; Productivity; Progress Reports; Publishing; Pupil; Reflex action; Regulation; Reporting; Research; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Rodent; Role; Schedule; Schools; Signal Transduction; Sleep; Sleep Disorders; Sleep Disorders Therapy; Slice; Space Perception; Subconscious; Synapses; Technology; Testing; Time; Update; Vertebrate Photoreceptors; Vision; Visual; Visual Perception; Visual system structure; Work; Workplace; alertness; base; combat; constriction; design; drug development; experience; feeding; fluorescence imaging; ganglion cell; imaging modality; improved; light intensity; melanopsin; prevent; receptor; research study; response; retinal bipolar neuron; retinal neuron; retinal rods; visual process; visual processing

One function of the visual system is to enable conscious perception of spatial details in tlie environment; this requires the rod and cone photoreceptor cells in the retina. The visual system also mediates subconscious, non-image-forming photic regulation of various physiological functions such as the pupil reflex and the resetting of our body clocks to the solar cycle. Failure to properly regulate these accessory visual responses results in a wide range of health problems including depression, sleep disorders, and even' cancer. Non-image-forming photoreception utilizes not only rods and cones but also the recently discovered ganglion-cell photoreceptors, i.e. the intrinsically photosensitive retinal ganglion cells (ipRGCs), Recent studies suggested that ipRGCs Interact bidirectionally with other retinal neurons: bipolar and amacrine cells feed rod/cone-driven light responses to ipRGCs, vifhile these ganglion cells signal their intrinsic photoresponses to bipolar and amacrine cells. This grant uses electrophysiological and imaging methods to study both directions of synaptic interactions In rodent retinas and comprises three goals: (1) To Identify ON bipolar cells that innervate the ipRGCs and analyze their light responses, through intracellular recordings from ON bipolar cells followed by fluorescence Imaging of intracellular dye fills; (2) To analyze the effects of amacrine-csll neuromodulators on ipRGCs, by testing chemicals that either activate or inhibit the receptors for these neuromodulators; and (3) To Identify bipolar and amacrine cells that receive synaptic Input from ipRGCs, by using intracellular recordings to search for light-sensitive bipolar and amacrine cells in rodless coneless retinas. Findings from these studies will enable a better understanding of how rod/cone signals regulate our body docks, the pupil reflex and other non-image-forming photosensory behaviors, and will also provide clues as to how the ipRGCs might modulate rod/cone circuits and hence conscious visual perception. This new knowledge may be useful for the development of drugs and light therapies for sleep problems and depression, the design of better workplace policies and school schedules to promote alertness and maximize productivity, and the development of healthier lighting technologies.

视觉系统的一个功能是能够有意识地感知环境中的空间细节；这 需要视网膜中的视杆和视锥感光细胞。视觉系统也调节潜意识， 对各种生理功能的非成像光调节，如瞳孔反射和 将我们的生物钟重新设置为太阳周期。未能适当地调节这些辅助视觉 反应会导致一系列的健康问题，包括抑郁、睡眠障碍，甚至 癌症。非成像光接收不仅利用视杆和视锥，而且还利用最近发现的 神经节细胞光感受器，即固有的光敏性视网膜神经节细胞(IpRGCs)，近年来 研究表明，ipRGCs与其他视网膜神经元双向相互作用：双极细胞和无长突细胞 视杆/视锥驱动的光对ipRGC的光反应，即这些神经节细胞发出其固有的信号 对双极细胞和无长突细胞的光反应。这笔赠款使用电生理和成像方法来 研究啮齿动物视网膜中突触相互作用的两个方向，包括三个目标：(1)识别 支配ipRGC并通过细胞内记录分析其光反应的双极细胞 对双极细胞进行荧光成像，然后对细胞内的染料进行填充；(2)分析 通过测试激活或抑制受体的化学物质，对ipRGC上的无长臂碱-csll神经调节剂进行研究 这些神经调节剂；以及(3)识别接受突触输入的双极和无长突细胞 IpRGCs，通过细胞内记录在无杆细胞中寻找光敏的双极和无长突细胞 无视锥视网膜。这些研究的发现将使我们能够更好地理解杆/锥信号是如何 调节我们的身体、瞳孔反射和其他非成像感光行为，并将 还提供了关于ipRGC如何调制视杆/视锥细胞回路从而调节有意识视觉的线索 感知力。这一新知识可能对开发睡眠药物和光疗法有用。 问题和抑郁，设计更好的工作场所政策和学校时间表，以促进 提高警觉性和最大限度地提高生产率，以及开发更健康的照明技术。