Department of Physiology, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94143-0444.
Department of Physiology, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, CA 94143-0444
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21812-21820. doi: 10.1073/pnas.1914661116. Epub 2019 Oct 7.
The developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure. To elucidate the relationship between synaptic remodeling and functional changes during this experience-dependent process, we used 2-photon microscopy to image synaptic structures of sparsely labeled layer 2/3 neurons in the binocular zone of mouse primary visual cortex. Anatomical changes at presynaptic and postsynaptic sites in mice undergoing monocular visual deprivation (MD) were compared to those in control mice with normal visual experience. We found that postsynaptic spines remodeled quickly in response to MD, with neurons more strongly dominated by the deprived eye losing more spines. These postsynaptic changes parallel changes in visual responses during MD and their recovery after restoration of binocular vision. In control animals with normal visual experience, the formation of presynaptic boutons increased during the critical period and then declined. MD affected bouton formation, but with a delay, blocking it after 3 d. These findings reveal intracortical anatomical changes in cellular layers of the cortex that can account for rapid activity-dependent plasticity.
发育中的大脑可以通过回路重组快速响应感觉体验的改变。在生命早期的一个关键时期,初级视觉皮层中的神经元对被遮挡的眼睛的反应迅速减弱,而对睁开的眼睛的反应则更好。虽然已经描述了这个过程的生理和一些分子机制,但除了众所周知的丘脑皮质投射变化之外,其结构基础仍然不清楚。为了阐明在这个经验依赖过程中突触重塑和功能变化之间的关系,我们使用双光子显微镜来成像小鼠初级视觉皮层双眼区稀疏标记的第 2/3 层神经元的突触结构。将经历单眼视觉剥夺 (MD) 的小鼠与具有正常视觉体验的对照小鼠的突触前和突触后部位的解剖变化进行了比较。我们发现,突触后棘在 MD 作用下迅速重塑,与剥夺眼更强主导的神经元失去更多的棘突。这些突触后变化与 MD 期间的视觉反应变化及其在双眼视觉恢复后的恢复相平行。在具有正常视觉体验的对照动物中,在关键时期内,突触前末梢的形成增加,然后减少。MD 影响末梢形成,但有延迟,在 3 天后阻断。这些发现揭示了皮质细胞层中的皮质内解剖变化,可以解释快速的活动依赖性可塑性。