Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Neurology Service, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
Nat Commun. 2023 Nov 11;14(1):7320. doi: 10.1038/s41467-023-43081-w.
Loss of nervous system tissue after severe brain injury is a main determinant of poor functional recovery. Cell transplantation is a promising method to restore lost tissue and function, yet it remains unclear if transplanted neurons can demonstrate the population level dynamics important for movement control. Here we present a comprehensive approach for long-term single neuron monitoring and manipulation of transplanted embryonic cortical neurons after cortical injury in adult male mice performing a prehension task. The observed patterns of population activity in the transplanted network strongly resembled that of healthy networks. Specifically, the task-related spatiotemporal activity patterns of transplanted neurons could be represented by latent factors that evolve within a low dimensional manifold. We also demonstrate reliable modulation of the transplanted networks using minimally invasive epidural stimulation. Our approach may allow greater insight into how restoration of cell-type specific network dynamics in vivo can restore motor function.
严重脑损伤后神经系统组织的丧失是功能恢复不良的主要决定因素。细胞移植是一种有前途的方法,可以恢复丢失的组织和功能,但仍不清楚移植的神经元是否可以表现出对运动控制很重要的群体水平动力学。在这里,我们提出了一种综合方法,用于在成年雄性小鼠执行抓握任务时对皮质损伤后移植的胚胎皮质神经元进行长期的单个神经元监测和操作。观察到的移植网络中的群体活动模式与健康网络非常相似。具体来说,移植神经元的与任务相关的时空活动模式可以通过在低维流形内演变的潜在因素来表示。我们还证明了使用微创硬膜外刺激对移植网络进行可靠的调制。我们的方法可能使我们更深入地了解体内恢复细胞类型特异性网络动力学如何恢复运动功能。