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Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

机译:脑卒中后恢复中针对特定神经回路的光遗传学方法

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摘要

Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered light-sensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.Electronic supplementary materialThe online version of this article (doi:10.1007/s13311-015-0411-5) contains supplementary material, which is available to authorized users.
机译:在美国,中风是导致死亡和残疾的主要原因,但是治疗选择却非常有限。功能恢复可以在中风后发生,部分归因于在梗塞附近或远程连接到梗塞区域的神经连接的重新布线。因此,对神经回路重新布线的更好理解是发展未来中风恢复治疗策略的重要一步。由于中风会破坏梗塞周围区域和远程连接区域的功能连接,因此研究中风后恢复过程中大脑范围的网络动态非常重要。光遗传学是一种革命性的神经科学工具,它使用生物工程化的光敏蛋白在毫秒内选择性激活或抑制特定的细胞类型和神经回路,从而为解剖疾病中的神经回路机制提供了更高的特异性和时间精度。在这篇综述中,我们讨论了中风后重映射和恢复的当前观点,包括最近的使用光遗传学研究中风后神经回路重映射以及光遗传刺激以增强中风恢复的研究。将光遗传学与其他读数结合使用的多峰方法(例如,体内神经成像技术,行为测定和下一代测序)将加深我们对中风后恢复过程中神经回路重组的理解,并提供有关哪些脑回路的重要见解电子补充材料本文的在线版本(doi:10.1007 / s13311-015-0411-5)包含补充材料,授权用户可以使用。

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