Veterans Affairs Boston Healthcare System, Harvard Medical School, West Roxbury, MA, 02132, USA.
Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Sci Rep. 2022 Jul 19;12(1):12278. doi: 10.1038/s41598-022-16478-8.
Non-invasive stimulation technologies are emerging as potential treatment options for a range of neurodegenerative disorders. Experimental evidence suggests that stimuli-evoked changes in slow brain rhythms may mitigate or even prevent neuropathological and behavioral impairments. Slow wave activity is prevalent during sleep and can be triggered non-invasively by sensory stimulation targeting the visual system or directly via activation of neurons locally using optogenetics. Here, we developed new tools for delivering visual stimulation using light-emitting diodes in freely moving mice while awake and during sleep. We compared these tools to traditional optogenetic approaches used for local stimulation of neurons in the cerebral cortex. We then used these tools to compare the effects of low-frequency visual versus optogenetic stimulations on the slow wave activity and sleep pattern in mice. Visual stimulation effectively enhanced slow wave activity without disrupting the sleep pattern. Optogenetic stimulation of cortical GABAergic neurons increased NREM sleep. These results suggest that visual stimulation can be effective at boosting slow wave activity without having adverse effects on sleep and thus holds great potential as a non-invasive stimulation treatment strategy.
非侵入性刺激技术正在成为一系列神经退行性疾病的潜在治疗选择。实验证据表明,刺激引起的慢波节律变化可能减轻甚至预防神经病理学和行为损伤。慢波活动在睡眠期间很常见,可以通过针对视觉系统的感觉刺激非侵入性地触发,也可以直接通过光遗传学激活局部神经元来触发。在这里,我们开发了新的工具,用于在清醒和睡眠期间通过发光二极管向自由移动的小鼠提供视觉刺激。我们将这些工具与传统的用于大脑皮层局部刺激神经元的光遗传学方法进行了比较。然后,我们使用这些工具比较了低频视觉刺激与光遗传学刺激对小鼠慢波活动和睡眠模式的影响。视觉刺激有效地增强了慢波活动,而不会破坏睡眠模式。光遗传学刺激皮层 GABA 能神经元增加了非快速眼动睡眠。这些结果表明,视觉刺激可以有效地增强慢波活动,而不会对睡眠产生不良影响,因此作为一种非侵入性刺激治疗策略具有很大的潜力。