Gianola Sara, Savio Tiziana, Schwab Martin E, Rossi Ferdinando
Department of Neuroscience, Rita Levi Montalcini Centre for Brain Repair, University of Turin, I-10125 Turin, Italy.
J Neurosci. 2003 Jun 1;23(11):4613-24. doi: 10.1523/JNEUROSCI.23-11-04613.2003.
The highly specific connection patterns of the mature CNS are shaped through finely regulated processes of axon growth and retraction. To investigate the relative contribution of cell-autonomous mechanisms and extrinsic cues in these events, we examined the development of Purkinje axon intracortical plexus in the rat cerebellum. During the first postnatal week, several new processes sprout from focal swellings along the initial portion of the Purkinje neurite and spread in the granular layer. Intense structural plasticity occurs during the following week, with pruning of collateral branches and remodeling of terminal arbors. The mature distribution of the Purkinje infraganglionic plexus, confined within the most superficial portion of the granular layer, is attained at approximately postnatal day 15. A similar neuritic branching pattern is also developed by Purkinje cells grown in cultures of dissociated cerebellar cells or transplanted to extracerebellar CNS regions, suggesting that cell-autonomous mechanisms contribute to determining the Purkinje axon phenotype. The structural remodeling of Purkinje intracortical plexus is concomitant with the development of cerebellar myelin. To ask whether myelin-associated factors contribute to the morphological maturation of Purkinje neurites, we prevented normal myelinogenesis by killing oligodendrocyte precursors with 5'-azacytidine or by applying neutralizing antibodies against the myelin-associated neurite growth inhibitor Nogo-A. In both conditions, Purkinje axons retained exuberant branches, and the terminal plexus spanned the entire extent of the granular layer. Thus, the formation of Purkinje axon collaterals is, in part, controlled by intrinsic determinants, but their growth and distribution are regulated by environmental signals, among which are myelin-derived cues.
成熟中枢神经系统高度特异的连接模式是通过轴突生长和回缩的精细调控过程形成的。为了研究细胞自主机制和外在信号在这些事件中的相对作用，我们研究了大鼠小脑浦肯野轴突皮质内神经丛的发育。在出生后的第一周，几个新的突起从小脑浦肯野神经元突起起始段的局灶性肿胀处发出，并在颗粒层中扩散。在接下来的一周，发生了强烈的结构可塑性变化，侧支被修剪，终末树突发生重塑。浦肯野神经节下神经丛的成熟分布局限于颗粒层最表层，大约在出生后第15天形成。在解离的小脑细胞培养物中生长或移植到小脑外中枢神经系统区域的浦肯野细胞也形成了类似的神经突分支模式，这表明细胞自主机制有助于确定浦肯野轴突的表型。浦肯野皮质内神经丛的结构重塑与小脑髓鞘的发育同时发生。为了探究髓鞘相关因子是否有助于浦肯野神经突的形态成熟，我们通过用5'-氮杂胞苷杀死少突胶质前体细胞或应用针对髓鞘相关神经突生长抑制因子Nogo-A的中和抗体来阻止正常的髓鞘形成。在这两种情况下，浦肯野轴突都保留了丰富的分支，终末神经丛跨越了颗粒层的整个范围。因此，浦肯野轴突侧支的形成部分受内在决定因素控制，但其生长和分布受环境信号调节，其中包括髓鞘衍生的信号。
