TRANSNEURONAL DEGENERATION IN THE CENTRAL NERVOUS SYSTEM

这项研究的长期目标是确定 开发的脆弱性背后的机制 神经元退化。对中枢神经系统的损害 结果轴突切断后神经元发生原发退行性变性。 继发性跨神经元变性可发生在 一个或两个突触上的神经元。主要和 跨神经元变性更有可能发生在损伤后的 与发生类似损伤时相比，正在发育的神经系统 成年人。在新生猫中，视皮质的消融会导致 背外侧膝状体细胞的原发变性 视网膜核团(DLGN)与跨神经元变性 神经节细胞。当成年猫的视觉皮质被消融时， DLGN中的细胞变性，而视网膜中的所有细胞 活下去。这些结果似乎表明，细胞是 仅在此期间易受跨神经元变性的影响 在它们和它们的突触连接成熟之前。 然而，尽管初级退行性变发生在视觉上 任何年龄的皮质消融，其速度和严重程度 幼年动物和成年动物的退化程度各不相同。因此， 目前尚不清楚神经元是否易受 因不成熟或不成熟而导致的跨神经元变性 跨神经元变性是否依赖于 原发退行性变的特点。在中国的实验 这项提议旨在检验这样一种假设 跨神经元变性是一个过程，只有发展到 神经元是脆弱的。首先，一个快速初选的模型 成年dLGN的退行性变将使用 神经毒素海人藻酸。因此，这种模式将剥夺成熟 视网膜神经节细胞的正常靶细胞以类似的方式 到新生儿的视皮层消融术。这将被用来 调查成人快速变性的后果 DLGN通过研究视网膜投射和连通性 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 对解释以前的工作和 指出了未来研究的方向。 神经元变性。这些实验将使用标准光 和电子显微镜技术来标记神经元通路 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.