An implantable neural probe with monolithically integrated dielectric waveguide and recording electrodes for optogenetics applications

Abstract

Objective Optogenetics promises exciting neuroscience research by offering optical stimulation of neurons with unprecedented temporal resolution, cell-type specificity and the ability to excite as well as to silence neurons. This work provides the technical solution to deliver light to local neurons and record neural potentials, facilitating local circuit analysis and bridging the gap between optogenetics and neurophysiology research. Approach We have designed and obtained the first in vivo validation of a neural probe with monolithically integrated electrodes and waveguide. High spatial precision enables optical excitation of targeted neurons with minimal power and recording of single-units in dense cortical and subcortical regions. Main results The total coupling and transmission loss through the dielectric waveguide at 473 nm was 10.5 ± 1.9 dB, corresponding to an average output intensity of 9400 mW mm−2 when coupled to a 7 mW optical fiber. Spontaneous field potentials and spiking activities of multiple Channelrhodopsin-2 expressing neurons were recorded in the hippocampus CA1 region of an anesthetized rat. Blue light stimulation at intensity of 51 mW mm−2 induced robust spiking activities in the physiologically identified local populations. Significance This minimally invasive, complete monolithic integration provides unmatched spatial precision and scalability for future optogenetics studies at deep brain regions with high neuronal density.

State-of-the-art MEMS and microsystem tools for brain research

“…Some of the first neural probes monolithically integrating both optical and electrical components are illustrated in Figures 4a-g. Figure 4 Example optoelectrodes with integrated waveguides: (a-c) Laser diode coupled waveguide probe demonstrating diode directly mounted on neural probe 165 ; (d) a digital micromirror directing multi-color light into waveguides terminated with metal-coated corner mirrors 171 ; (e) single waveguide on a silicon recording array 162 ; (f and g) schematic of multi-color laser diodes coupled from a PCB using graded-index lenses and mixed on the neural probe and micrograph of an actual device 166 ; and (h) a 4x4 ZnO array demonstrating a very similar form factor as the Utah array with the added capability of optical stimulation through the ZnO tine and ITO-coated tip 109 .…”

“…In these devices, an optical waveguide is integrated onto the probe shank to deliver light from an externally coupled optical source to a stimulation site at the center of an integrated electrode array 162 . The waveguide can be made out of polymers such as SU-8 (Refs.…”

“…The waveguide can be made out of polymers such as SU-8 (Refs. 163,164) or dielectrics 162 and has a small rectangular light emission area on the order of 100 μm 2 . The lithographically defined waveguide has a precisely positioned stimulation site relative to the recording sites to provide the spatial resolution necessary for circuit mapping (Figure 4e).…”

“…The probe shank dimensions are defined with micron resolution using a double-sided DRIE process on an SOI wafer. Even a simple design having a single waveguide and eight electrode sites can demonstrate the utility of optogenetics from a highdensity population such as the CA1 pyramidal layer in a rat by optically inducing single-unit activity from two cell types, which can be distinguished by the relative timing between the induced spikes and the light stimuli 162 .…”

Direct interfacing of neurons to highly integrated microsystems

“…A sensor site and the surrounding stimulation site can be seen in Fig. 1b Besides the comparably large, planar in-vitro systems, which are in the focus of this contribution, there are also CMOS-based needle-type probes for recording and stimulation in vivo that have been pioneered at the University of Michigan [3,[29][30][31][32][33] and adopted by other groups ( Figure 2) [34][35][36][37]. Such electrode arrays are inserted into the living brain and facilitate advances in the understanding of the nervous system.…”