DEVELOPMENT AND REGENERATION OF THE VERTEBRATE RETINA

尽管脊椎动物视网膜的突触和功能组织 人们都很清楚，对细胞机制知之甚少 调节神经分化、成熟和突触形成。我们 最近使用了神经递质特有的特性，如摄取， 作为生理和解剖探针的合成和释放 非洲爪哇和兔已鉴定神经元和突触的发育 视网膜。我们发现，对于所检查的每一种视网膜传输器 (GABA、甘氨酸和多巴胺)的产生和成熟。 发射机特定的属性遵循特定的时间模式。 此外，神经元的承诺成为GABA能，甘氨酸能 和多巴胺能出现在其他基因表达之前的许多阶段 目前可用的形态和生理标记。因此， 特定于发射器的属性可能是需要遵循的强大工具 形态和化学上的早期分化事件也是如此 随着已鉴定神经元的成熟。因此，在接下来的五年里， 几年后，我们计划继续并扩大这些研究。主要有6种 目的：(1)胆碱能和某些疾病的发育规律 将对兔视网膜中的肽能神经元进行表征和比较 与GABA能、甘氨酸能和多巴胺能系统的同源性。(2) GABA能、甘氨酸能和多巴胺能细胞的分化和成熟 兔视网膜中的突触之后会有一系列的 ~3H-递质的高亲和力摄取与电子显微镜 放射自显影。(3)突触后的发育模式 其中一些递质和多肽的受体将通过 结合分析和功能分析。(4)我们对正常视网膜的研究结果 将以发展为基础，考察具体措施的效果 扰动，例如已识别的细胞类型添加的选择损伤 某些传送器和药物到达视网膜，以及光-和 暗培养，对各种递质特异性神经元的发育。 (5)非洲爪哇胚胎视网膜将被分离成单个细胞， 这些细胞中特定于发射器的属性的开发将是 其次是组织培养。(6)成年蝾螈的视网膜再生 也将使用神经递质作为探针进行研究。

Although the synaptic and functional organization of the vertebrate retina is fairly well understood, little is known about the cellular mechanisms regulating neuromal differentiation, maturation and synaptogenesis. We have recently used neurotransmitter-specific properties such as uptake, synthesis and release as physiological and anatomical probes to follow the development of identified neurons and synapses in the Xenopus and rabbit retinas. We found that for each of the retinal transmitters examined (GABA, glycine and dopamine), the emergence and maturation of transmitter-specific properties follow a characteristic temporal pattern. Furthermore, the commitments of neurons to become GABAergic, glycinergic and dopaminergic occur many stages prior to the expression of other currently available morphological and physiological markers. Thus, transmitter-specific properties may be powerful tools to follow morphologically and chemically the early events of differentiation as well as maturation of identified neurons. Accordingly, over the next five years, we plan to continue and extend these studies. There are 6 main objectives: (1) The developmental patterns for cholinergic and certain peptidergic neurons in the rabbit retina will be characterized and compared with those of GABAergic, glycinergic and dopaminergic systems. (2) The differentiation and maturation of GABAergic, glycinergic and dopaminergic synapses in the rabbit retina will be followed by a combination of high-affinity uptake of 3H-transmitters and electronic microscope autoradiography. (3) The developmental patterns of the post-synaptic receptors for some of these transmitters and peptides will be examined by binding and functional assays. (4) Our results on normal retinal development will be used as the basis to examine the effects of specific perturbations, such as selection lesion of an identified cell type addition of certain transmitters and drugs to the retinas, as well as light- and dark-rearings, on the development of various transmitter-specific neurons. (5) Embryonic Xenopus retinas will be dissociated into single cells and the development of transmitter-specific properties in these cells will be followed in tissue culture. (6) Retinal regeneration in the adult newt will also be studied using neurotransmitters as probes.