Development, Involution and Plasticity in the Central Nervous System

Smith, Carolyn

Abstract

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.