PEPTIDERGIC NEURONS OF THE PRIMATE RETINA

这项研究的长期目标是了解肽能 神经元有助于灵长类动物视网膜中的信息处理。视网膜 以前认为肽主要作为神经调节剂， 免疫反应性肽在宽视野无长突中的定位， 联合和网间细胞，使他们的大部分 与无长突细胞的接触似乎支持这一假设。期间 然而，在第一次赠款期间，发现一些肽能无长突蛋白使 与双极细胞和神经节细胞广泛接触。最引人注目的 早期关于肽功能的概括的例外是 将肽定位到一种类型的双极细胞。这些结果在 第一批研究表明，肽能细胞不仅 与视觉信息的最直接途径相互作用;它们还 似乎被组成它的细胞用作神经递质， 通路在本更新申请中提出的实验中， 重点将从肽本身转向肽的功能， 包含它们的细胞。光学显微镜双标记实验将是 旨在识别每一个细胞中的化学信使的完整补充， 细胞的类型基于这些结果，电子显微镜双标记 实验将被设计成识别与细胞接触的细胞。 肽能神经元和回路中的其他神经元将被识别 通过电子显微照片的连续重建。冷冻固定研究 视网膜将决定肽是否储存在，大概， 从突触囊泡中释放出来光学显微镜技术的发展 猕猴视网膜也将应用于人类视网膜， 本研究结果为进一步研究脑内肽能神经元提供了基础。 患病的眼睛最近的研究显示视网膜肽水平的变化 在实验诱导糖尿病后，这些神经元可能是 选择性地受到视网膜疾病的影响。建议的实验， 肽能双极细胞特别可能具有临床 相关性，因为它们似乎接触短波长锥。的 短波长系统在早期阶段特别脆弱， 一些视网膜疾病，并建议对突触的基础研究， 该途径中的相互作用可能有助于解释 赤字

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.