Patterned photostimulation via visible-wavelength photonic probes for deep brain optogenetics
Optogenetic methods developed over the past decade enable unprecedented optical activation and silencing of specific neuronal cell types. However, light scattering in neural tissue precludes illuminating areas deep within the brain via free-space optics; this has impeded employing optogenetics universally. Here, we report an approach surmounting this significant limitation. We realize implantable, ultranarrow, silicon-based photonic probes enabling the delivery of complex illumination patterns deep within brain tissue. Our approach combines methods from integrated nanophotonics and microelectromechanical systems, to yield photonic probes that are robust, scalable, and readily producible en masse. Their minute cross sections minimize tissue displacement upon probe implantation. We functionally validate one probe design in vivo with mice expressing channelrhodopsin-2. Highly local optogenetic neural activation is demonstrated by recording the induced response—both by extracellular electrical recordings in the hippocampus and by two-photon functional imaging in the cortex of mice coexpressing GCaMP6.
© 2016 SPIE. Paper 16055SSR received Aug. 2, 2016; accepted for publication Oct. 24, 2016; published online Dec. 6, 2016. E.S. was supported by the Kavli Prize Postdoctoral Fellowship in Nanoscience. This work was supported by the NSF Award No. 1265055, DARPA Award No. W911NF-14-1-0006, and NIH Director's Pioneer Awards (MLR and AST). We gratefully acknowledge facilitation of our prototype probe fabrication by the Kavli Nanoscience Institute at Caltech. We thank Gustavo Rios for helpful discussions.
Published - NPH_4_1_011002.pdf