Department of Neurology, Washington University in St. Louis, St. Louis, MO 63130.
Department of Radiology, Washington University in St. Louis, St. Louis, MO 63130.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9952-E9961. doi: 10.1073/pnas.1711789114. Epub 2017 Oct 30.
Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism.
数十年的实验动物研究表明,在视觉皮层正常感觉诱发电位发育的关键时期,视觉经验非常重要。然而,对于早期视觉经验对自发活动系统水平组织的影响,人们知之甚少。人类静息态 fMRI 研究表明,自发活动中的亚慢波波动在整个大脑中呈现出一种刻板的时空模式。此外,自发亚慢波活动(ISA)的组织具有可塑性,它可以通过学习和经验来调节,这表明在关键时期对变化更加敏感。在这里,我们使用小鼠的宽场光学内源信号成像来研究全皮层自发 ISA 模式。通过单眼或双眼视觉剥夺,我们研究了关键期视觉经验对 ISA 相关性和潜伏期模式在皮层静息态网络内和跨网络发展的影响。通过单眼眼睑缝合进行视觉修饰会降低视觉网络内左右皮质之间的相关性(同型相关),但对网络间相关性影响不大。相比之下,双眼眼睑缝合导致视觉同型相关增加,视觉网络与几个非视觉网络之间的负相关增加,表明存在跨模态可塑性。在 Arc 基因缺失的小鼠中,这些网络水平的变化明显减弱,Arc 是一种已知对活性依赖性突触可塑性至关重要的基因。综上所述,我们的研究结果表明,关键期视觉经验通过 Arc 依赖的机制诱导自发 ISA 关系的全局变化,包括在视觉网络内和跨网络。