de Lima Ana D, Gieseler Anne, Voigt Thomas
Developmental Physiology, Institute of Physiology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Dev Neurobiol. 2009;69(2-3):105-23. doi: 10.1002/dneu.20696.
Available evidence converges to suggest that during the early development of the cerebral cortex, the emergence of the spontaneous network activity chronologically overlap with the end of the cell migration period in the developing cortex. We approached the functional regulation of neuronal migration in a culture model of neocortical networks, using time lapses to detect migratory movements, calcium-imaging to assess the activity of migratory neurons, and immunocytochemical methods to identify the migratory cells retrospectively. In cell cultures, early physiological development and cell migration are reproduced at a local network level, thus allowing the study of the interrelationships between cell migration and network development independent of the topographical complexity. Neurons migrate at least until 12 days in vitro and GABAergic neurons migrate faster compared with non-GABAergic neurons. A decline of migratory activity was coincident with the development of spontaneous synchronous network activity. Migrating interneurons did not participate in synchronous network activity, but interneurons that ended cell migration during observation time frequently engaged in synchronous activity within less than an hour. Application of GABA(A) and ionotropic glutamate receptor antagonists significantly increased the number of migrating GABAergic neurons without changing the dynamics of the migratory movements. Thus, neurotransmitters released by early network activity might favor the termination of neuronal migration. These results reinforce the idea that network activity plays an important role in the development of late-born GABAergic cells.
现有证据表明，在大脑皮层的早期发育过程中，自发网络活动的出现与发育中皮层细胞迁移期的结束在时间上相互重叠。我们在新皮层网络的培养模型中研究神经元迁移的功能调节，利用延时摄影检测迁移运动，通过钙成像评估迁移神经元的活性，并采用免疫细胞化学方法追溯性地识别迁移细胞。在细胞培养中，早期生理发育和细胞迁移在局部网络水平上得以重现，从而能够独立于地形复杂性研究细胞迁移与网络发育之间的相互关系。神经元至少在体外培养12天时仍在迁移，与非GABA能神经元相比，GABA能神经元迁移速度更快。迁移活动的下降与自发同步网络活动的发展同时发生。正在迁移的中间神经元不参与同步网络活动，但在观察期内结束细胞迁移的中间神经元常在不到一小时内频繁参与同步活动。应用GABA(A)和离子型谷氨酸受体拮抗剂可显著增加迁移的GABA能神经元数量，而不改变迁移运动的动力学。因此，早期网络活动释放的神经递质可能有利于神经元迁移的终止。这些结果强化了网络活动在晚期生成的GABA能细胞发育中起重要作用这一观点。
