Abstract
Optogenetics has potential applications in the study of epilepsy and neuroprostheses, and for studies on neural circuit dynamics. However, to achieve translation to clinical usage, optogenetic interfaces that are capable of chronic stimulation and monitoring with minimal brain trauma are required. We aimed to develop a chronically implantable device for photostimulation of the brain of non-human primates. We used a micro-light-emitting diode (LED) array with a flexible polyimide film. The array was combined with a whole-cortex electrocorticographic (ECoG) electrode array for simultaneous photostimulation and recording. Channelrhodopsin-2 (ChR2) was virally transduced into the cerebral cortex of common marmosets, and then the device was epidurally implanted into their brains. We recorded the neural activity during photostimulation of the awake monkeys for 4 months. The neural responses gradually increased after the virus injection for ~8 weeks and remained constant for another 8 weeks. The micro-LED and ECoG arrays allowed semi-invasive simultaneous stimulation and recording during long-term implantation in the brains of non-human primates. The development of this device represents substantial progress in the field of optogenetic applications.
Highlights
Optogenetic approaches enable the control of neural activity using light-sensitive receptors, which are genetically introduced to neurons
ChR2V was expressed in the membrane of the cells, whereas neuron-specific nuclear protein (NeuN) expression was observed in the nuclei and cytoplasm of neuronal cells
Merged images showed that the ChR2V was expressed in the membrane of the NeuN-labeled cells, which meant that the expression of ChR2 successfully occurred in neurons
Summary
Optogenetic approaches enable the control of neural activity using light-sensitive receptors, which are genetically introduced to neurons. This technology provides many distinct advantages, including millisecond temporal precision (Han and Boyden, 2007; Boyden, 2015), cell-type specificity (Han et al, 2009; Nathanson et al, 2009), and elimination of electrical artifacts (Zhang et al, 2007). Optogenetic approaches have a clear advantage over electrical and electromagnetic stimulation in animal studies of clinical applications, as well as for investigating neural circuit dynamics. Most current systems for combined stimulation and recording rely on the use of “optrodes,” which are penetrating electrodes combined with optical fibers (Gradinaru et al, 2007). To allow stable monitoring and stimulation at many sites, some recent studies have used a micro-electrocorticographic (μECoG) array combined with micro-light-emitting
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