A distinctive property of the cerebellar system is olivocerebellar modules, where synchronized electrical activity in neurons in the inferior olivary nucleus (IO) evokes organized activity in the cerebellar cortex. However, the exact function of these modules, and how they are developed, is still largely unknown. Here we show that the IO in in vitro slices from postnatal mice spontaneously generates clusters of neurons with synchronous Ca 2+ transients. Neurons in the principal olive (PO), and the vestibular-related dorsomedial cell column (dmcc), showed an age-dependent increase in spontaneous calcium transients. The spatiotemporal activity pattern was occasionally organized in clusters of co-active neighbouring neurons, with regular (16 min -1) and irregular (2-3 min -1) repeating cluster activity in the dmcc and PO, respectively. IO clusters had a diameter of 100-170 μm, lasted ~1 s, and increased in occurrence from postnatal day P5.5 to P12.5, followed by a sharp drop to near zero at P15.5. IO clusters were overlapping, and comprised nearly identical neurons at some time points, and a varied subset of neurons at others. Some neurons had hub-like properties, being co-active with many other neighbours, and some were co-active with separate clusters at different times. The coherence between calcium transients in IO neurons decreased with Euclidean distance between the cells reaching low values at 100-200 μm distances. Intracellular recordings from IO neurons during cluster formation revealed the presence of spikelet-like potentials, suggesting that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. In conclusion, the IO shows spontaneous cluster activity under in vitro conditions, coinciding with a critical postnatal period in olivocerebellar development. We propose that these clusters may be forerunners of the ensembles of IO neurons shown to be co-active in adult animals spontaneously and during motor acts.
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机译：小脑系统的一个独特特性是小脑小脑模块，其中下橄榄核（IO）中神经元的同步电活动引起小脑皮层的有组织活动。但是，这些模块的确切功能以及如何开发仍然未知。在这里，我们显示来自出生后小鼠的体外切片中的IO自发生成具有同步Ca 2+瞬变的神经元簇。主橄榄（PO）和前庭相关的背膜细胞列（dmcc）中的神经元显示自发钙瞬变的年龄依赖性增加。时空活动模式偶尔组织在附近的共同活跃神经元的簇中，在dmcc和PO中分别有规律地（16 min -1）和不规则（2-3 min -1）重复的簇活动。 IO簇的直径为100-170μm，持续约1 s，并且从出生后P5.5到P12.5的发生率增加，然后在P15.5急剧下降到接近零。 IO簇重叠，在某些时间点包含几乎相同的神经元，在其他时间点包含不同的神经元子集。一些神经元具有类似集线器的特性，与许多其他邻居共同活动，而另一些则在不同时间与单独的簇共同活动。 IO神经元中钙瞬变之间的相干性随着细胞之间的欧几里得距离在100-200μm距离处达到低值而降低。在簇形成过程中，来自IO神经元的细胞内记录显示出小穗样电位的存在，这表明相邻IO神经元之间的电耦合可能是一种同步机制。总之，IO在体外条件下显示出自发的簇活动，这与小骨小脑发育的关键产后时期相吻合。我们建议这些簇可能是IO神经元集合的先驱者，这些神经元在成年动物中自发地和在运动过程中表现为共同活跃。
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