Brian McGovern

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

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.

A New Individually Addressable Micro-LED Array for Photogenetic Neural Stimulation

Here, we demonstrate the use of a micro light emitting diode (LED) array as a powerful tool for complex spatiotemporal control of photosensitized neurons. The array can generate arbitrary, 2-D, excitation patterns with millisecond and micrometer resolution. In particular, we describe an active matrix control address system to allow simultaneous control of 256 individual micro LEDs. We present the system optically integrated into a microscope environment and patch clamp electrophysiology. The results show that the emitters have sufficient radiance at the required wavelength to stimulate neurons expressing channelrhodopsin-2 (ChR2).

A Processing Platform for Optoelectronic/Optogenetic Retinal Prosthesis

The field of retinal prosthesis has been steadily developing over the last two decades. Despite the many obstacles, clinical trials for electronic approaches are in progress and already demonstrating some success. Optogenetic/optoelectronic retinal prosthesis may prove to have even greater capabilities. Although resolutions are now moving beyond recognition of simple shapes, it will nevertheless be poor compared to normal vision. If we define the aim to be to return mobility and natural scene recognition to the patient, it is important to maximize the useful visual information we attempt to transfer. In this paper, we highlight a method to simplify the scene, perform spatial image compression, and then apply spike coding. We then show the potential for translation on standard consumer processors. The algorithms are applicable to all forms of visual prosthesis, but we particularly focus on optogenetic approaches.

Arrays of MicroLEDs and Astrocytes: Biological Amplifiers to Optogenetically Modulate Neuronal Networks Reducing Light Requirement

In the modern view of synaptic transmission, astrocytes are no longer confined to the role of merely supportive cells. Although they do not generate action potentials, they nonetheless exhibit electrical activity and can influence surrounding neurons through gliotransmitter release. In this work, we explored whether optogenetic activation of glial cells could act as an amplification mechanism to optical neural stimulation via gliotransmission to the neural network. We studied the modulation of gliotransmission by selective photo-activation of channelrhodopsin-2 (ChR2) and by means of a matrix of individually addressable super-bright microLEDs (μLEDs) with an excitation peak at 470 nm. We combined Ca2+ imaging techniques and concurrent patch-clamp electrophysiology to obtain subsequent glia/neural activity. First, we tested the μLEDs efficacy in stimulating ChR2-transfected astrocyte. ChR2-induced astrocytic current did not desensitize overtime, and was linearly increased and prolonged by increasing μLED irradiance in terms of intensity and surface illumination. Subsequently, ChR2 astrocytic stimulation by broad-field LED illumination with the same spectral profile, increased both glial cells and neuronal calcium transient frequency and sEPSCs suggesting that few ChR2-transfected astrocytes were able to excite surrounding not-ChR2-transfected astrocytes and neurons. Finally, by using the μLEDs array to selectively light stimulate ChR2 positive astrocytes we were able to increase the synaptic activity of single neurons surrounding it. In conclusion, ChR2-transfected astrocytes and μLEDs system were shown to be an amplifier of synaptic activity in mixed corticalneuronal and glial cells culture.

Photostimulator for optogenetic retinal prosthesis

The discovery that neurons can be photostimulated via genetic incorporation of artificial opsins offers potential for many new forms of neural prosthesis. In this work, we demonstrate a photostimulator which has both the irradiance requirement and the spatial resolution for retinal prosthesis. We characterise its electrical and optical properties and show its ability to accurately stimulate individual action potentials.

Seeing the light: a photonic visual prosthesis for the blind

This paper highlights how the genetic incorporation of artificial opsins into the retina can lead to a new class of retinal prosthesis. We demonstrate the efficacy of incorporating channelrhodopsin into neuron cells in-vitro and show how that can be scaled to in-vivo. We show that we need typically 100mW/cm2 of instantaneous light intensity on the neuron in order to stimulate action potentials which results in 10W/cm2 required from the light source. We thus use GaN LED arrays to provide spatially controlled stimulation which is of sufficient brightness to stimulate the cells.

An optogenetic neural stimulation platform for concurrent induction and recording of neural activity

The precise control of neural activity afforded by the use of light sensitive ion channels such as Channel Rhodopsin (ChR2) offers neuroscientists the means to devise new experiments. In this paper we present the Optogenetic Neural Stimulation (ONS) platform which enables complex in-vitro or ex-vivo investigation of neural activity. The platform is based on micro-meter sized Light Emitting Diodes (LEDs) integrated onto a single Gallium Nitrite chip. Mounted onto a microscope system, this system can be used to carry out experiments on networks of cells, or on sub-cellular regions of a neuron with millisecond timing and micrometer resolution.

Optoelectronic microarrays for retinal prosthesis

In this work we demonstrate the use of optoelectronic Gallium Nitride LED micro arrays for optical neural stimulation. We demonstrate the ability to control these sufficiently to transfer a spike coded ‘image’ to arrays of channelrhodopsin-2 photosensitized cells. We also show how this initial work is scalable from in-vitro towards a long term optoelectronic system for optogenetic retinal prosthesis.