Schilling K, Schmidt H H, Baader S L
Abteilung Anatomie und Zellbiologie, Universität Ulm, Germany.
Neuroscience. 1994 Apr;59(4):893-903. doi: 10.1016/0306-4522(94)90293-3.
The developmental expression and cellular distribution of nitric oxide synthase was investigated in the murine cerebellum and in cerebellar neurons developing under controlled in vitro conditions. Cerebellar granule cells expressed nitric oxide synthase only after migration to the internal granule cell layer. Initially, the nascent internal granule cell layer throughout the cerebellum stained uniformly for nitric oxide synthase, but during the second postnatal week, a pattern emerged consisting of clusters of heavily stained granule cells separated by areas of unstained granule cells. This pattern persisted into adulthood. There was a close temporal correlation between innervation of the granule cell layer by mossy fibers and the emergence of granule cell compartments as defined by levels of nitric oxide synthase expression. Granule cells in dissociated cultures derived from cerebellar anlagen prior to mossy fiber innervation also express nitric oxide synthase. The time-course of nitric oxide expression was independent of electrical activity of the neuronal network forming in vitro. However, suppression of spontaneous electrical activity resulted in enhanced nitric oxide synthase expression. These findings indicate that granule cell precursors are endowed with an intrinsic program which regulates nitric oxide synthase induction and which is executed independently of correct positional cues. The data also suggest that electrical activity of ingrowing mossy fibers down regulates nitric oxide synthase expression and plays an important role in the generation of granule cell compartments. These compartments may contribute to the functional organization of the cerebellar cortex.
研究了一氧化氮合酶在小鼠小脑以及在体外受控条件下发育的小脑神经元中的发育表达和细胞分布。小脑颗粒细胞仅在迁移至内颗粒层后才表达一氧化氮合酶。最初，整个小脑新生的内颗粒层对一氧化氮合酶呈均匀染色，但在出生后第二周，出现了一种模式，即由大量染色的颗粒细胞簇被未染色的颗粒细胞区域分隔开。这种模式持续到成年期。苔藓纤维对颗粒细胞层的支配与由一氧化氮合酶表达水平所定义的颗粒细胞区室的出现之间存在密切的时间相关性。在苔藓纤维支配之前从小脑原基分离培养的颗粒细胞也表达一氧化氮合酶。一氧化氮表达的时间进程与体外形成的神经元网络的电活动无关。然而，自发电活动的抑制导致一氧化氮合酶表达增强。这些发现表明颗粒细胞前体具有一种内在程序，该程序调节一氧化氮合酶的诱导，并且独立于正确的位置线索而执行。数据还表明，向内生长的苔藓纤维的电活动下调一氧化氮合酶表达，并在颗粒细胞区室的形成中起重要作用。这些区室可能有助于小脑皮质的功能组织。
