Bando Yuki, Irie Katsumasa, Shimomura Takushi, Umeshima Hiroki, Kushida Yuki, Kengaku Mineko, Fujiyoshi Yoshinori, Hirano Tomoo, Tagawa Yoshiaki
Department of Biophysics, Kyoto University Graduate School of Science, Kyoto 606-8502, Japan.
CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Cereb Cortex. 2016 Jan;26(1):106-117. doi: 10.1093/cercor/bhu180. Epub 2014 Aug 11.
Neural activity plays roles in the later stages of development of cortical excitatory neurons, including dendritic and axonal arborization, remodeling, and synaptogenesis. However, its role in earlier stages, such as migration and dendritogenesis, is less clear. Here we investigated roles of neural activity in the maturation of cortical neurons, using calcium imaging and expression of prokaryotic voltage-gated sodium channel, NaChBac. Calcium imaging experiments showed that postmigratory neurons in layer II/III exhibited more frequent spontaneous calcium transients than migrating neurons. To test whether such an increase of neural activity may promote neuronal maturation, we elevated the activity of migrating neurons by NaChBac expression. Elevation of neural activity impeded migration, and induced premature branching of the leading process before neurons arrived at layer II/III. Many NaChBac-expressing neurons in deep cortical layers were not attached to radial glial fibers, suggesting that these neurons had stopped migration. Morphological and immunohistochemical analyses suggested that branched leading processes of NaChBac-expressing neurons differentiated into dendrites. Our results suggest that developmental control of spontaneous calcium transients is critical for maturation of cortical excitatory neurons in vivo: keeping cellular excitability low is important for migration, and increasing spontaneous neural activity may stop migration and promote dendrite formation.
神经活动在皮质兴奋性神经元发育的后期阶段发挥作用，包括树突和轴突的分支、重塑以及突触形成。然而，其在早期阶段，如迁移和树突发生中的作用尚不清楚。在这里，我们使用钙成像和原核电压门控钠通道NaChBac的表达来研究神经活动在皮质神经元成熟中的作用。钙成像实验表明，II/III层的迁移后神经元比迁移神经元表现出更频繁的自发钙瞬变。为了测试这种神经活动的增加是否可能促进神经元成熟，我们通过NaChBac的表达提高了迁移神经元的活性。神经活动的升高阻碍了迁移，并在神经元到达II/III层之前诱导了领先进程的过早分支。许多在皮质深层表达NaChBac的神经元没有附着在放射状胶质纤维上，这表明这些神经元已经停止迁移。形态学和免疫组织化学分析表明，表达NaChBac的神经元的分支领先进程分化为树突。我们的结果表明，自发钙瞬变的发育控制对于体内皮质兴奋性神经元的成熟至关重要：保持细胞兴奋性低对迁移很重要，而增加自发神经活动可能会停止迁移并促进树突形成。
