Washington University Pain Center and.
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA, Washington University School of Medicine, St. Louis, MO, USA.
Pain. 2017 Nov;158(11):2108-2116. doi: 10.1097/j.pain.0000000000000968.
The advent of optogenetic tools has allowed unprecedented insights into the organization of neuronal networks. Although recently developed technologies have enabled implementation of optogenetics for studies of brain function in freely moving, untethered animals, wireless powering and device durability pose challenges in studies of spinal cord circuits where dynamic, multidimensional motions against hard and soft surrounding tissues can lead to device degradation. We demonstrate here a fully implantable optoelectronic device powered by near-field wireless communication technology, with a thin and flexible open architecture that provides excellent mechanical durability, robust sealing against biofluid penetration and fidelity in wireless activation, thereby allowing for long-term optical stimulation of the spinal cord without constraint on the natural behaviors of the animals. The system consists of a double-layer, rectangular-shaped magnetic coil antenna connected to a microscale inorganic light-emitting diode (μ-ILED) on a thin, flexible probe that can be implanted just above the dura of the mouse spinal cord for effective stimulation of light-sensitive proteins expressed in neurons in the dorsal horn. Wireless optogenetic activation of TRPV1-ChR2 afferents with spinal μ-ILEDs causes nocifensive behaviors and robust real-time place aversion with sustained operation in animals over periods of several weeks to months. The relatively low-cost electronics required for control of the systems, together with the biocompatibility and robust operation of these devices will allow broad application of optogenetics in future studies of spinal circuits, as well as various peripheral targets, in awake, freely moving and untethered animals, where existing approaches have limited utility.
光遗传学工具的出现使得人们能够以前所未有的方式深入了解神经元网络的组织。尽管最近开发的技术已经实现了在自由活动的、未束缚的动物中进行脑功能研究的光遗传学,但无线供电和设备耐用性在脊髓回路研究中仍然是一个挑战,因为在这些研究中,动态的、多维的运动与坚硬和柔软的周围组织相作用,可能导致设备退化。我们在这里展示了一种完全可植入的光电设备,它采用近场无线通信技术供电,具有薄而灵活的开放式架构,提供了出色的机械耐用性、对生物流体渗透的坚固密封以及无线激活的保真度,从而可以长期对脊髓进行光学刺激,而不会限制动物的自然行为。该系统由一个双层矩形磁线圈天线和一个微尺度无机发光二极管(μ-ILED)组成,连接在一个薄而灵活的探针上,探针可以植入小鼠脊髓的硬脑膜上方,以便有效地刺激背角中表达光敏感蛋白的神经元。通过脊髓 μ-ILED 对 TRPV1-ChR2 传入神经进行无线光遗传学激活会引起伤害感受行为,并在动物身上进行稳健的实时位置回避,持续操作时间可长达数周至数月。控制这些系统所需的低成本电子设备,以及这些设备的生物相容性和稳健运行,将允许光遗传学在未来对脊髓回路以及各种外周靶点的研究中得到广泛应用,而现有的方法在清醒、自由活动和未束缚的动物中应用受限。