TRANSNEURONAL DEGENERATION IN THE CENTRAL NERVOUS SYSTEM

这项研究的长期目标是确定 发展中国家脆弱性的根本机制 神经元退化。 中枢神经系统损伤 导致轴突切断的神经元的原发性逆行变性。 亚连续性跨神经元变性可发生， 一个或两个突触之间的神经元。 小学和 transneuronal变性更有可能遵循损伤的 神经系统的发展比当类似的伤害发生在 成年人 在新生猫中，视觉皮层的消融导致 背外侧膝状体细胞的原发性变性 核（dLGN）和β视网膜变性的跨神经元变性 神经节细胞 当成年猫的视觉皮层被切除时， dLGN中的细胞退化，而视网膜中的所有细胞 生存 这些结果似乎表明，细胞 易受跨神经元变性的影响， 在它们和它们的突触连接达到成熟之前。 然而，尽管原发性变性发生在视觉上， 任何年龄的皮质消融， 退化在幼年和成年动物之间是不同的。 因此，我们认为， 目前尚不清楚神经元是否对 由于它们的不成熟而发生跨神经元变性， 跨神经元变性是否依赖于 原发性退化的特征。 中的实验 这一提议旨在检验以下假设： 跨神经元变性是一个过程， 神经元是脆弱的。 第一，快速初级模型 成人dLGN中的变性将使用 神经毒素红藻氨酸 这种模式将剥夺成熟的 视网膜神经节细胞的正常靶细胞以类似的方式 到新生儿的视觉皮层消融。 这将用于 研究成年后快速退化的后果 dLGN通过研究视网膜投影和连接， dLGN，以及不同神经节细胞的存活 人口。 这些实验的结果将提供 对解释以前的工作至关重要的信息， 未来研究的方向， 神经元变性 实验将使用标准光 和电子显微镜技术来标记神经通路 并量化突触连接的各个方面。

The longterm goal of this research is to determine the mechanisms which underlie the vulnerability of developing neurons to degeneration. Damage to the central nervous system results in primary retrograde degeneration of axotomized neurons. Subs equent transneuronal degeneration can occur to involve neurons across one or two synapses. Both primary and transneuronal degeneration are more likely to follow injury to the developing nervous system than when comparable injury occurs in the adult. In the neonatal cat, ablation of visual cortex results in primary degeneration of cells in the dorsal lateral geniculate nucleus (dLGN) and transneuronal degeneration of beta retinal ganglion cells. When visual cortex is ablated in the adult cat, cells in the dLGN degenerate whereas all cells in the retina survive. These results would seem to show that cells are vulnerable to transneuronal degeneratation only during the period before they and their synaptic connections have reached maturity. However, although primary degeneration occurs following visual cortex ablation at any age, the speed and severity of this degeneration varies between young and adult animals. Therefore, it is unclear at present whether neurons are susceptible to transneuronal degeneration because of their immaturity or whether transneuronal degeneration is dependent on the characteristics of the primary degeneration. The experiments in this proposal are designed to test the hypothesis that transneuronal degeneration is a process to which only developing neurons are vulnerable. First, a model for rapid primary degeneration in the adult dLGN will be developed using the neurotoxin kainic acid. This model will thus deprive mature retinal ganglion cells of their normal target cells in a similar way to visual cortex ablation in the neonate. This will be used to investigate the consequences of rapid degeneration in the adult dLGN by studying retinal projections and connectivity in the dLGN, as well as the survival of different ganglion cell populations. The results from these experiments will provide information essential to the interpretation of previous work and to the direction of future research into the mechanisms of neuronal degeneration. The experiments will use standards light and electron microscopy techniques to label neuronal pathways and quantify aspects of synaptic connectivity.