PEPTIDERGIC NEURONS OF THE PRIMATE RETINA

灵长类动物视网膜的肽能神经元

• 批准号: 3262652
• 负责人: DAVID W MARSHAK
• 金额: $ 15.07万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-05-01 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3262652
• 关键词: Macaca; amacrine cells; aspartate; cholecystokinin; cone cell; corticotropin releasing factor; dendrites; electron microscopy; glutamates; glycine; histochemistry /cytochemistry; immunochemistry; neural information processing; neuroanatomy; neuropeptide Y; neuropeptides; neurophysiology; neurotransmitters; retina; retinal bipolar neuron; somatostatin; substance P; synapses; synaptic vesicles; visual feedback

The long-term goal of this research is to understand how peptidergic neurons contribute to information processing in the primate retina. Retinal peptides were previously thought to act primarily as neuromodulators, and the localizations of immunoreactive peptides in wide-field amacrine, associational and interplexiform cells that made the majority of their contacts with amacrine cells seemed to support this hypothesis. During the first grant period, however, some peptidergic amacrine were found to make extensive contacts with bipolar and ganglion cells. The most striking exception to the earlier generalizations about peptide function was the localization of a peptide to a type of bipolar cell. These results in the first grant period suggested that peptidergic cells are not only interacting with the most direct pathway for visual information; they also appear to be used as neurotransmitters by the cells that comprise that pathway. In the experiments proposed in this application for renewal, the emphasis will shift from the peptides, themselves, to the functions of the cells that contain them. Light microscopic double label experiments will be designed to identify the full complement of chemical messengers in each type of cell. Based on those results, electron microscopic double label experiments will be designed to identify the cells contacted by the peptidergic neurons, and other neurons in the circuits will be identified by serial reconstruction of electron micrographs. Studies with cryofixed retina will determine whether peptides are stored in and, presumably, released from synaptic vesicles. The light microscopic techniques developed for the macaque monkey retina will also be applied to the human retina, and the results would provide the basis for studies of peptidergic neurons in diseased eyes. Recent studies showing changes in retinal peptide levels after experimentally induced diabetes suggest that these neurons may be selectively affected by retinal diseases. The proposed experiments with peptidergic bipolar cells are particularly likely to have clinical relevance since they appear to contact the short wavelength cones. The short wavelength system is particularly vulnerable in the early stages of a number of retinal diseases, and the proposed basic research on the synaptic interactions in that pathway might facilitate the interpretation of the deficits.

这项研究的长期目标是了解肽能 神经元参与灵长类视网膜的信息处理。视网膜 此前，多肽被认为主要作为神经调节剂，并且 免疫活性多肽在广野无长突体内的定位， 联结和网间细胞使它们的大部分 与无长突细胞的接触似乎支持这一假设。在.期间 然而，在第一次授权期内，发现一些多肽能无花果碱能使 广泛接触双极细胞和神经节细胞。最引人注目的 关于多肽函数的早期推广的例外是 将一种多肽定位于一种双极细胞。这些结果在 首次授权期表明，肽能细胞不仅 与视觉信息最直接的途径互动；他们还 似乎被组成它的细胞用作神经递质 路径。在此续期申请中提出的实验中， 重点将从多肽本身转移到多肽的功能 包含它们的单元格。光学显微镜双标记实验将是 旨在识别每个化学信使的全部补充物 单元格的类型。根据这些结果，电子显微镜双标记 实验将被设计用来识别与 肽能神经元，以及回路中的其他神经元将被识别 通过电子显微图像的连续重建。冷冻固定的研究 视网膜将决定多肽是否储存在视网膜中， 从突触小泡中释放出来。发展起来的光学显微镜技术 因为猕猴的视网膜也将应用于人类的视网膜，以及 这些结果将为进一步研究大鼠脑内肽能神经元奠定基础。 有病的眼睛。最近的研究表明视网膜多肽水平的变化 在实验诱导的糖尿病后提示这些神经元可能是 选择性地受到视网膜疾病的影响。建议进行的实验 肽能双极细胞尤其有可能具有临床 因为它们似乎接触到了短波长锥体，所以与此相关。这个 短波长系统在早期阶段尤其脆弱 视网膜疾病的数量以及对突触的拟议基础研究 该途径中的相互作用可能有助于解释 赤字。