Vanni Matthieu P, Chan Allen W, Balbi Matilde, Silasi Gergely, Murphy Timothy H
Department of Psychiatry, Brain Research Centre, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada.
Department of Psychiatry, Brain Research Centre, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada
J Neurosci. 2017 Aug 2;37(31):7513-7533. doi: 10.1523/JNEUROSCI.3560-16.2017. Epub 2017 Jul 3.
Connectivity mapping based on resting-state activity in mice has revealed functional motifs of correlated activity. However, the rules by which motifs organize into larger functional modules that lead to hemisphere wide spatial-temporal activity sequences is not clear. We explore cortical activity parcellation in head-fixed, quiet awake GCaMP6 mice from both sexes by using mesoscopic calcium imaging. Spectral decomposition of spontaneous cortical activity revealed the presence of two dominant frequency modes (<1 and ∼3 Hz), each of them associated with a unique spatial signature of cortical macro-parcellation not predicted by classical cytoarchitectonic definitions of cortical areas. Based on assessment of 0.1-1 Hz activity, we define two macro-organizing principles: the first being a rotating polymodal-association pinwheel structure around which activity flows sequentially from visual to barrel then to hindlimb somatosensory; the second principle is correlated activity symmetry planes that exist on many levels within a single domain such as intrahemispheric reflections of sensory and motor cortices. In contrast, higher frequency activity >1 Hz yielded two larger clusters of coactivated areas with an enlarged default mode network-like posterior region. We suggest that the apparent constrained structure for intra-areal cortical activity flow could be exploited in future efforts to normalize activity in diseases of the nervous system. Increasingly, functional connectivity mapping of spontaneous activity is being used to reveal the organization of the brain. However, because the brain operates across multiple space and time domains a more detailed understanding of this organization is necessary. We used wide-field calcium imaging of the indicator GCaMP6 in head-fixed, awake mice to characterize the organization of spontaneous cortical activity at different spatiotemporal scales. Correlation analysis defines the presence of two to three superclusters of activity that span traditionally defined functional territories and were frequency dependent. This work helps define the rules for how different cortical areas interact in time and space. We provide a framework necessary for future studies that explore functional reorganization of brain circuits in disease models.
基于小鼠静息态活动的连接图谱揭示了相关活动的功能基序。然而，这些基序如何组织成更大的功能模块，进而形成半球范围的时空活动序列，其规则尚不清楚。我们通过介观钙成像技术，对雌雄头固定、安静清醒的GCaMP6小鼠的皮质活动进行了划分。自发皮质活动的频谱分解显示存在两种主导频率模式（<1 Hz和~3 Hz），每种模式都与皮质大区域划分的独特空间特征相关，而这并非由经典的皮质区域细胞构筑定义所预测。基于对0.1 - 1 Hz活动的评估，我们定义了两个宏观组织原则：第一个原则是一个旋转的多模态关联风车结构，活动围绕该结构从视觉区域依次流向桶状区域，然后流向后肢体感区域；第二个原则是相关活动对称平面，其存在于单个区域内的多个层面，如感觉和运动皮质的半球内反射。相比之下，频率大于1 Hz的较高频率活动产生了两个更大的共同激活区域簇，其中一个后区域类似默认模式网络且有所扩大。我们认为，未来在神经系统疾病中进行活动归一化的努力，可以利用区域内皮质活动流的明显受限结构。越来越多的自发活动功能连接图谱被用于揭示大脑的组织架构。然而，由于大脑在多个空间和时间域中运作，因此有必要对这种组织架构有更详细的了解。我们使用头固定、清醒小鼠中指示剂GCaMP6的宽场钙成像技术，来表征不同时空尺度下自发皮质活动的组织架构。相关性分析确定了两到三个跨越传统定义功能区域的活动超簇，且这些超簇与频率相关。这项工作有助于确定不同皮质区域在时间和空间上如何相互作用的规则。我们提供了一个未来研究探索疾病模型中脑回路功能重组所需的框架。
