Multi-site optical excitation using ChR2 and micro-LED array

Abstract

Studying neuronal processes such as synaptic summation, dendritic physiology and neural network dynamics requires complex spatiotemporal control over neuronal activities. The recent development of neural photosensitization tools, such as channelrhodopsin-2 (ChR2), offers new opportunities for non-invasive, flexible and cell-specific neuronal stimulation. Previously, complex spatiotemporal control of photosensitized neurons has been limited by the lack of appropriate optical devices which can provide 2D stimulation with sufficient irradiance. Here we present a simple and powerful solution that is based on an array of high-power micro light-emitting diodes (micro-LEDs) that can generate arbitrary optical excitation patterns on a neuronal sample with micrometre and millisecond resolution. We first describe the design and fabrication of the system and characterize its capabilities. We then demonstrate its capacity to elicit precise electrophysiological responses in cultured and slice neurons expressing ChR2.

Holographic optogenetic stimulation of patterned neuronal activity for vision restoration

“…This could be highly desirable for neuro-photonic applications of optogenetic technology 1,2 including optogenetic retinal prostheses [3][4][5][6][7][8][9] , because sensory information is generally represented in distributed spatio-temporal patterns of activity carried across large populations of neurons, while neighbouring neurons in real circuits are often found to have widely divergent response properties. Although electrical retinal prostheses are already being used to aid blind human subjects, it appears that their ultimate performance/resolution may be limited by current spread, and the acuity of B20/2,000 is common to both 60 electrode epiretinal and 1,500 electrode sub-retinal systems.…”

“…A pattern photo-stimulation system for artificially controlling neural activity in a vision prosthesis or for general neurostimulation applications is not expected to have this limitation (due to minimal light scattering in the inner retinal layers) and will ideally allow cellular-resolution, rapid, massively parallel, light-efficient stimulation across macroscopic (millimeter-scale) coverage areas. To date, however, optical excitation of optogenetically targeted populations is often delivered nonspecifically to the whole population using wide-field flashes with intense lamps 1,3,10 , LEDs (light-emitting diodes) and optical fibre coupled illumination 11,12 or in simple patterns using rapid random-access laser deflection 13,14 , digital micromirror arrays 8,9,[15][16][17][18] and micro-LED arrays 6,19 .…”

Emerging Gene Therapies for Retinal Degenerations

“…These glasses have an array of sensitive light detectors, much like the detectors in a conventional video camera. The detectors drive an array of micro-LEDs, which then emit the proper wavelength and intensity of light (Grossman et al, 2010) to activate the NpHR that has been transduced into the cones via AAV. This work is moving forward toward a Phase 1 clinical trial, and will be using AAV with NpHR driven by a human cone promoter (Roska et al, personal communication).…”

52-1:Invited Paper: OLED Microdisplays Control Cell Behavior through Optogenetics

“…OLED microdisplays represent the culmination of this process. By integration with complementary metal-oxide semiconductor (CMOS) backplane driver electronics, it has become possible to produce arrays of >10 5 individually addressable OLEDs with each OLED pixel measuring well under 10 × 10 µm 2 . The primary use of these devices so far has been in 'near eye' applications, i.e.…”

“…In addition, stimulation at multiple sites has also been achieved with bundles of optical fibers and with µLED arrays. [4,5] However, only small numbers of separate excitation spots were demonstrated and the resolution of both approaches may be fundamentally limited [6]. In addition, fabrication of the µLED arrays requires relatively complex semiconductor technology.…”