Whitman Mary C, Greer Charles A
Yale University School of Medicine, Department of Neurobiology, New Haven, CT 06520-8082, United States of America.
Prog Neurobiol. 2009 Oct;89(2):162-75. doi: 10.1016/j.pneurobio.2009.07.003. Epub 2009 Jul 15.
Though initially described in the early 1960s, it is only within the past decade that the concept of continuing adult neurogenesis has gained widespread acceptance. Neuroblasts from the subventricular zone (SVZ) migrate along the rostral migratory stream (RMS) into the olfactory bulb, where they differentiate into interneurons. Neuroblasts from the subgranular zone (SGZ) of the hippocampal formation show relatively little migratory behavior, and differentiate into dentate gyrus granule cells. In sharp contrast to embryonic and perinatal development, these newly differentiated neurons must integrate into a fully functional circuit, without disrupting ongoing performance. Here, after a brief historical overview and introduction to olfactory circuitry, we review recent advances in the biology of neural stem cells, mechanisms of migration in the RMS and olfactory bulb, differentiation and survival of new neurons, and finally mechanisms of synaptic integration. Our primary focus is on the olfactory system, but we also contrast the events occurring there with those in the hippocampal formation. Although both SVZ and SGZ neurogenesis are involved in some types of learning, their full functional significance remains unclear. Since both systems offer models of integration of new neuroblasts, there is immense interest in using neural stem cells to replace neurons lost in injury or disease. Though many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. We discuss here some of the central features of these advances, as well as speculate on future research directions.
尽管在20世纪60年代初就有了最初的描述,但直到过去十年,成体神经发生持续存在的概念才得到广泛认可。来自脑室下区(SVZ)的神经母细胞沿着吻侧迁移流(RMS)迁移到嗅球,在那里它们分化为中间神经元。海马结构颗粒下区(SGZ)的神经母细胞迁移行为相对较少,并分化为齿状回颗粒细胞。与胚胎期和围生期发育形成鲜明对比的是,这些新分化的神经元必须整合到一个功能完备的神经回路中,且不能干扰正在进行的神经活动。在此,在对嗅觉神经回路进行简要的历史概述和介绍之后,我们回顾了神经干细胞生物学、RMS和嗅球中的迁移机制、新神经元的分化与存活,以及最终的突触整合机制等方面的最新进展。我们主要关注嗅觉系统,但也将那里发生的事件与海马结构中的事件进行对比。尽管SVZ和SGZ的神经发生都参与了某些类型的学习,但其全部功能意义仍不清楚。由于这两个系统都提供了新神经母细胞整合过程的模型,因此人们对利用神经干细胞替代因损伤或疾病而丢失的神经元有着极大的兴趣。尽管许多问题仍未得到解答,但关于成体神经发生、调控机制以及子代命运的新见解每天都在出现。我们在此讨论这些进展的一些核心特征,并对未来的研究方向进行推测。