DEVELOPMENT, INVOLUTION AND PLASTICITY IN THE CENTRAL NERVOUS SYSTEM

本项目旨在研究与神经系统发育、可塑性和内化相关的生化事件。我们使用定量放射自显影[1- 14C]亮氨酸方法来研究在这些事件中发生的神经系统组织变化的起源位置和过程，并使用[14C]脱氧葡萄糖方法来检查变化的结果，即功能重组。我们对大鼠正常出生后发育的研究表明，从第10天到成年阶段，大多数大脑区域的蛋白质合成率都在下降，除了下丘脑的室旁核和视上核，它们的蛋白质合成率在发育过程中增加，在成年时达到峰值。绵羊的正常胎儿发育伴随着蛋白质合成率的总体增加，这可能是由于绵羊的产前髓鞘形成。小鼠体感觉系统的“须到桶”通路被作为神经可塑性的模型。脱氧葡萄糖对新生小鼠须卵泡去除的影响的研究结果表明，当受损小鼠成年后，体感觉皮层和三叉脑干核的代谢图谱都发生了改变。当成年小鼠同样受到损伤时，160天后皮质桶区的代谢图谱也发生了改变。通过对比支配须囊周围神经纤维的数量，发现成年小鼠须囊周围神经纤维可能发生重组；也就是说，原来支配病变卵泡的纤维现在支配新的目标，即邻近的卵泡。在新生损伤小鼠中没有发现这种多余的神经支配，假设在新生儿中中枢神经系统发生了重组。这些结果表明小鼠新生和成年须桶通路的功能重组，并表明该系统可能作为发育和成年可塑性的有用模型。-可塑性退化须到桶途径胎儿发育脱氧葡萄糖法产后发育

The purpose of this project is to study the biochemical events associated with development, plasticity and involution of the nervous system. We have used the quantitative autoradiographic [1- 14C]leucine method to study the sites of origin and the processes underlying changes in nervous system organization that take place during these events and the [14C]deoxyglucose method to examine the outcome of the changes, i.e. the functional reorganization. Our studies of normal postnatal development in rats show decreasing rates of protein synthesis in most brain regions from day 10 to the adult stage except in the paraventricular and supraoptic nuclei of the hypothalamus in which rates of protein synthesis increased during development reaching peak values in adults. Normal fetal development in the sheep is accompanied by overall increases in rates of protein synthesis probably due to prenatal myelination in the sheep. The whisker-to-barrel pathway of the mouse somatosensory system has served as our model of neural plasticity. Results of deoxyglucose studies on the effects of whisker follicle removal in neonatal mice show that when the lesioned mice reach adulthood metabolic maps in both somatosensory cortex and in trigeminal brainstem nuclei are altered. When adult mice are similarly lesioned metabolic maps in the cortical barrel field are also found to be altered after 160 days. Comparison of the number of nerve fibers innervating whisker follicles adjacent to those that had been lesioned suggests that in adult mice some reorganization may occur in the periphery; i.e., fibers that had originally innervated the lesioned follicles now innervated new targets, the adjacent follicles. In the neonatally lesioned mice no such supernumerary innervation was found and it is hypothesized that in the neonate the reorganization had taken place in the central nervous system. These results indicate functional reorganization in both the neonatal and the adult whisker-barrel pathway in the mouse and they suggest that this system may serve as a useful model of both developmental and adult plasticity. - plasticity involution whisker-to-barrel pathway fetal development deoxyglucose method postnatal development