Methods for Spatial Analysis of Microcolumns in Cortex

描述(由申请者提供)：针对研究主题18.功能性衰老： 在这项应用中，我们建议采用和验证源自统计和凝聚态物理的自动化、用户友好的方法，以量化皮质神经元的局部空间组织。特别是，我们的目的是通过计算微柱宽度、微柱间距、微柱内神经元密度和微柱有序的强度来量化神经元的局部微柱组织。这些关于局部微柱组织的定量信息将使我们能够检验以下假设：(1)不同皮质区域的微柱属性显著不同；(2)尽管没有显著的神经元丢失，但正常衰老时微柱组织被破坏；(3)年龄引起的微柱组织的变化与年龄相关的认知减退有关。在我们的研究中，我们将验证我们的方法并将我们的方法应用于Nissl染色的30微米厚的大脑皮层三个区域的冰冻切片：(A)位于主沟下岸的前额叶皮质46区，(B)位于颞上沟下方的颞下区域TE区，以及(C)海马旁回的TL区。之所以选择这些皮质区域，是因为它们可能与正常衰老时观察到的认知障碍有关，而且在显微镜下观察时，它们的微柱状程度明显不同。我们将在10只年轻恒河猴和10只老年恒河猴身上比较这三个区域的微柱属性，这些恒河猴之前已经进行了行为测试，以评估学习、识别记忆和执行系统功能。然后，我们将使用回归分析来确定年龄诱导的微柱属性的变化是否与这些认知领域中的任何一个领域的变化有关。

DESCRIPTION (provided by applicant): In response to Research Topic 18. Functional Senescence: In this application we propose to adapt and validate automated, user friendly methods derived from statistical and condensed matter physics to quantify the local spatial organization of neurons in the cortex. In particular, our aim is to quantify the local microcolumnar organization of neurons by calculating the microcolumnar width, intermicrocolumnar distance, neuronal density within the microcolumn and the strength of microcolumnar order. This quantitative information on local microcolumnar organization will allow us to test the following hypotheses: (1) microcolumnar properties differ significantly across diverse cortical regions, (2) microcolumnar organization is disrupted in normal aging despite non-significant neuronal loss, (3) age-induced changes in microcolumnar organization are correlated with age-related cognitive decline. In our study we will validate and apply our methods to Nissl-stained, 30 microns thick frozen sections from three regions of the cerebral cortex: (a) area 46 of the prefrontal cortex in the lower bank of sulcus principalis, (b) area TE of the inferior temporal region below the superior temporal sulcus, and (c) area TL of the parahippocampal gyrus. These cortical regions were selected because they are potentially associated with cognitive impairments observed in normal aging and because they clearly differ in the degree of microcolumnarity when visually inspected under the microscope. We will compare the microcolumnar properties of these three regions in ten young and ten aged rhesus monkeys which have been previously behaviorally tested to assess learning, recognition memory, and executive system function. We will then use a regression analysis to determine if age-induced changes in microcolumar properties are related to alterations on any of these cognitive domains.