SPATIAL SEGREGATION BETWEEN POPULATIONS OF PONTO-CEREBELLAR NEURONS - STATISTICAL-ANALYSIS OF MULTIVARIATE SPATIAL INTERACTIONS

SPATIAL SEGREGATION BETWEEN POPULATIONS OF PONTO-CEREBELLAR NEURONS - STATISTICAL-ANALYSIS OF MULTIVARIATE SPATIAL INTERACTIONS
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DOI:
10.1002/ar.1092310413
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发表时间:
1991-12-01
期刊:
影响因子:
--
通讯作者:
BRODAL, P
BRODAL, P
中科院分区:
医学4区
文献类型:
--
作者:
BJAALIE, JG;DIGGLE, PJ;BRODAL, P

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本研究应用术语和方法来描述多变量空间点模式之间的空间相互作用,据我们所知,这在神经生物学中是新的。我们考虑两类点,类型1和2,分布在一定的参考体积(如脑干或皮质区的核)。例如,这些点可以代表不同类别的标记细胞或终止的轴突区域。我们说,有空间中立点之间的类型1和2,如果类型是签署的随机标签。如果一种机制驱动两个点类别在一起,我们说点模式是正相关的。相反,如果一个机制驱动类型1和类型2的点分开,我们说它们是分离的。通过比较两个点间距离的累积分布函数,我们可以区分中性、正关联和隔离。一个函数H12(t)是类型1和2的一对随机选择的点之间的距离t的累积分布函数。另一个是H 00(t),它是随机选择的一对点的对应函数,不涉及类型。这两个函数之间的估计差异的图给出了正关联、中性或隔离的指示。基于随机(中性)分布的模拟的统计检验可以用来观察偏离中性分布是否显著。我们将上述分析应用于大脑的一个主要通路,即脑桥-小脑投射。脑桥核中不同类型的细胞用荧光示踪剂罗丹明-B-异硫氰酸盐、荧光金和固蓝逆行标记。示踪剂注射在小脑旁小叶的邻近或更远的叶中。记录标记细胞胞体的位置,并在动态图形工作站上进行三维重建和显示。我们问是否不同的单位(叶)在paraflocculus接收信息从同一个群体,从两个不同的正相关的群体,或从分离的细胞群体。我们发现一个统计学上显着的趋势,细胞群投影到相邻的叶子是正相关的,虽然有几个细胞含有多个标签。神经元投射到叶宽分开的人口显着分离。从检查的重建,使用实时旋转,我们发现,标记的神经元的集群往往积累在壳或lamellae在脑桥。在板层内,细胞聚集成簇和带,其间有空孔(含有未标记的脑桥-小脑细胞体,可能投射到其他小脑靶点)。通过确定每个细胞群的参考平面的平均距离,我们发现,细胞群转移在腹内侧方向的注射部位从内侧部分的背侧parafleculus向外侧部分,并进入腹侧parafleculus。因此,我们得出结论,有一个连续的转变,在脑桥小脑细胞群的位置,对应于特定的变化,在小脑的目标区域。
This study applies terms and methods for describing spatial interactions between multivariate spatial point patterns, which are, to our knowledge, new in neurobiology. We consider two categories of points, type 1 and 2, distributed within a certain reference volume (such as a nucleus of the brainstem or a cortical area). The points may, for example, represent different categories of labelled cells or axonal fields of termination. We say that there is spatial neutrality between points of type 1 and 2 if the types are signed by random labelling. If a mechanism drives the two point categories together, we say that the point patterns are positively associated. Conversely, if a mechanism drives type 1 and 2 points apart, we say that they are segregated. By comparing two cumulative distribution functions of distances between points, we can distinguish neutrality, positive association, and segregation. One function, H12(t), is the cumulative distribution function of the distance t between a pair of randomly selected points of type 1 and 2. The other, H00(t), is the corresponding function for a pair of points randomly selected without reference to type. Plots of the estimated difference between these two functions give an indication of positive association, neutrality, or segregation. A statistical test, based on simulations of random (neutral) distributions, can be used to see whether deviations from neutrality are significant.We apply the analysis described above to a major pathway of the brain, namely the ponto-cerebellar projection. Different types of cells in the pontine nuclei are retrogradely labelled with the fluorescent tracers Rhodamine-B-isothiocyanate, Fluoro-Gold, and Fast Blue. The tracers are injected in adjacent or more distant folia of the cerebellar paraflocculus. The location of the somata of labelled cells are recorded and the total distribution reconstructed in three dimensions and displayed on a dynamic graphics workstation. We ask whether different units (folia) in the paraflocculus receive information from the same population, from two different positively associated populations, or from segregated cell populations. We find a statistically significant tendency for cell populations projecting to adjacent folia to be positively associated, although there are few cells containing multiple labels. Populations of neurons projecting to folia wider apart are significantly segregated. From inspections of the reconstructions, using real-time rotations, we find that the swarms of labelled neurons tend to accumulate in shells or lamellae in the pons. Within the lamellae, the cells are aggregated in clusters and bands with empty holes (containing unlabelled ponto-cerebellar cell bodies, presumably projecting to other cerebellar targets) in between. By determining the average distance to a reference plane for each cell population, we find that cell populations shift in a ventro-medial direction as the injection sites move from the medial part of the dorsal paraflocculus toward the lateral part and into the ventral paraflocculus. We therefore conclude that there is a continuous shift in location of ponto-cerebellar cell populations, corresponding to specific shifts in cerebellar target regions.