DEVELOPMENT, INVOLUTION AND PLASTICITY IN THE CENTRAL NERVOUS SYSTEM

这个项目的目的是研究与神经系统发育、可塑性和退化有关的生化事件。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神经系统组织发生变化的起始点和过程，并用[14C]脱氧葡萄糖方法来研究这些变化的结果，即功能重组。我们对大鼠出生后正常发育的研究表明，从第10天到成人期，大多数脑区的蛋白质合成速率都在下降，下丘脑室旁核和视上核除外，在发育过程中蛋白质合成速率增加，在成年时达到峰值。绵羊正常的胎儿发育伴随着蛋白质合成率的总体增加，这可能是由于绵羊出生前的髓鞘形成所致。小鼠躯体感觉系统的胡须到桶的通路已经成为我们的神经可塑性的模型。脱氧葡萄糖对新生小鼠去除胡须毛囊效果的研究结果表明，当小鼠成年后，躯体感觉皮质和三叉神经脑干核团的代谢图谱都发生了变化。当成年小鼠受到类似的损害时，大脑皮质桶区域的代谢图谱也被发现在160天后发生了变化。将支配胡须毛囊的神经纤维的数量与受损毛囊相邻的神经纤维数量进行比较表明，成年小鼠的周围可能发生了一些重组；即最初支配受损毛囊的纤维现在神经支配新的靶点，即邻近的毛囊。在新生儿受损的小鼠中，没有发现这种额外的神经支配，并假设在新生儿中，中枢神经系统发生了重组。这些结果表明，在小鼠的新生儿和成年胡须桶途径中都有功能重组，它们表明该系统可以作为发育和成年可塑性的有用模型。-可塑性退化胡须到桶途径胎儿发育脱氧葡萄糖方法出生后发育

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