Optogenetic surface stimulation of the rat cervical spinal cord

被引:15
作者
Mondello, S. E. [1 ,5 ]
Sunshine, M. D. [1 ,5 ]
Fischedick, A. E. [1 ]
Dreyer, S. J. [5 ,7 ]
Horwitz, G. D. [3 ,4 ,6 ]
Anikeeva, P. [5 ,8 ,9 ]
Horner, P. J. [10 ]
Moritz, C. T. [1 ,2 ,3 ,4 ,5 ,6 ]
机构
[1] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA
[2] Univ Washington, Inst Neuroengn, Seattle, WA 98195 USA
[3] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA
[4] Univ Washington, Grad Program Neurosci, Seattle, WA 98195 USA
[5] Ctr Sensorimotor Neural Engn, Seattle, WA USA
[6] Washington Natl Primate Res Ctr, Seattle, WA USA
[7] Univ Illinois, Dept Bioengn, Chicago, IL USA
[8] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA
[9] MIT, Elect Res Lab, Cambridge, MA 02139 USA
[10] Houston Methodist Res Inst, Dept Neurol Surg, Ctr Neuroregenerat, Houston, TX USA
基金
美国国家科学基金会;
关键词
brain-machine interface; hemiparesis; neuroprosthesis; optogenetics; spinal cord injury; EPIDURAL STIMULATION; CLINICAL-TRIAL; IN-VIVO; INTRASPINAL MICROSTIMULATION; NERVOUS-SYSTEM; GENE-THERAPY; LUMBAR CORD; INJURY; MOVEMENTS; ORGANIZATION;
D O I
10.1152/jn.00461.2017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Electrical intraspinal microstimulation (ISMS) at various sites along the cervical spinal cord permits forelimb muscle activation, elicits complex limb movements and may enhance functional recovery after spinal cord injury. here, we explore optogenetic spinal stimulation (OSS) as a less invasive and cell type-specific alternative to ISMS. To map forelimb muscle activation by OSS in rats. adeno-associated viruses (AAV) carrying the blue-light sensitive ion channels channelrhodopsin-2 (ChR2) and Chronos were injected into the cervical spinal cord at different depths and volumes. Following an AAV incubation period of several weeks, OSS-induced forelimb muscle activation and movements were assessed at 16 sites along the dorsal surface of the cervical spinal cord. Three distinct movement types were observed. We find that AAV injection volume and depth can be titrated to achieve OSS-based activation of several movements. Optical stimulation of the spinal cord is thus a promising method for dissecting the function of spinal circuitry and targeting therapies following injury. NEW & NOTEWORTHY Optogenetics in the spinal cord can be used both for therapeutic treatments and to uncover basic mechanisms of spinal cord physiology. For the first time, we describe the methodology and outcomes of optogenetic surface stimulation of the rat spinal cord. Specifically, we describe the evoked responses of forelimbs and address the effects of different adeno-associated virus injection paradigms. Additionally, we are the first to report on the limitations of light penetration through the rat spinal cord.
引用
收藏
页码:795 / 811
页数:17
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