Tsai Philbert S, Kaufhold John P, Blinder Pablo, Friedman Beth, Drew Patrick J, Karten Harvey J, Lyden Patrick D, Kleinfeld David
Department of Physics, Center for Neural Circuits and Behavior, and Graduate Program in Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.
J Neurosci. 2009 Nov 18;29(46):14553-70. doi: 10.1523/JNEUROSCI.3287-09.2009.
It is well known that the density of neurons varies within the adult brain. In neocortex, this includes variations in neuronal density between different lamina as well as between different regions. Yet the concomitant variation of the microvessels is largely uncharted. Here, we present automated histological, imaging, and analysis tools to simultaneously map the locations of all neuronal and non-neuronal nuclei and the centerlines and diameters of all blood vessels within thick slabs of neocortex from mice. Based on total inventory measurements of different cortical regions ( approximately 10(7) cells vectorized across brains), these methods revealed: (1) In three dimensions, the mean distance of the center of neuronal somata to the closest microvessel was 15 mum. (2) Volume samples within lamina of a given region show that the density of microvessels does not match the strong laminar variation in neuronal density. This holds for both agranular and granular cortex. (3) Volume samples in successive radii from the midline to the ventral-lateral edge, where each volume summed the number of cells and microvessels from the pia to the white matter, show a significant correlation between neuronal and microvessel densities. These data show that while neuronal and vascular densities do not track each other on the 100 mum scale of cortical lamina, they do track each other on the 1-10 mm scale of the cortical mantle. The absence of a disproportionate density of blood vessels in granular lamina is argued to be consistent with the initial locus of functional brain imaging signals.
众所周知，成人大脑内神经元的密度存在差异。在新皮层中，这种差异包括不同层之间以及不同区域之间神经元密度的变化。然而，微血管的伴随变化在很大程度上仍未被探明。在此，我们展示了自动化的组织学、成像和分析工具，用于同时绘制小鼠新皮层厚切片内所有神经元和非神经元细胞核的位置以及所有血管的中心线和直径。基于对不同皮质区域的总体测量（跨大脑矢量化约10^7个细胞），这些方法揭示了：（1）在三维空间中，神经元胞体中心到最近微血管的平均距离为15μm。（2）给定区域各层内的体积样本表明，微血管密度与神经元密度的强烈层间变化不匹配。这在无颗粒皮层和颗粒皮层中均成立。（3）从中线到腹外侧边缘的连续半径方向上的体积样本，其中每个体积汇总了从软膜到白质的细胞和微血管数量，显示神经元密度与微血管密度之间存在显著相关性。这些数据表明，虽然在新皮层100μm尺度的层间，神经元和血管密度并不相互对应，但在1 - 10mm尺度的皮质区域，它们确实相互对应。颗粒层中血管密度没有不成比例的情况，这被认为与功能性脑成像信号的初始位置一致。
