By: Dr. Michael Johnson
Optogenetics is a method that combines genetic and optic approaches to control the electrical activity of excitable cells (neurons and muscle fibers). This method is based on implementation of specific light-sensitive proteins which are called opsins. These trans-membrane proteins change their conformation under light with a specific wavelength (390-700 nm) and as a result ionic currents flow across the cell membrane. In turn, positively-charged (cations) or negatively-charged (anions) ionic movements lead to cell depolarization or hyperpolarization. Optogenetics uses different opsins, but preferably Channelrhodopsin-2. Channelrhodopsin-2 (ChR2, cation channels, responsive to 470 nm wavelength blue light) are applied for excitatory responses. In contrast, inhibitory responses can be evoked by activating Archaerhodopsin and Halorhodopsin (Arch, light-driven proton pump, responsive to 566 nm wavelength yellow light , HR, transmembrane chloride ion-pump, responsive to 580 nm wavelength yellow light). As a result, the activity of neuronal cells can be changed just under the light of a specific wavelength. The idea to use light for selective control of neural activity in different brain cells was formulated by Francis Crick during a lecture at the University of California at San Diego in 1999(Crick, 1979). In 2002, Professor GeroMizenbёkfor the first time postulated the principles of optogenetic method, which allow to control genetically modified nerve cells by the light. A few years later Karl Deisserothfrom Stanford University described optogenetic technology, caused a great interest in scientific community
Photostimulation of neurons
Photo-stimulation of neurons is an emerging field of research. Neuronal firing is achieved by shining a focused light source onto the nerve cell, causing it to depolarize. There are two major ways to approach this goal: irradiation of the neurons with a laser, inducing a local temperature gradient; and the introduction of light sensitive channels or receptors into the nerve cell making it sensitive to light, similar to rods and cones in the human retina. Advantages over the traditionally used electric stimulation are increased precision and less to no tissue trauma.
Electric vs Optic stimulations
Electric stimulation has inherent limitations compared to optic stimulation. To elicit reliable firing the electrodes have to be in physical contact with or in close proximity to the targeted tissue. Introduction of electrodes into the nerve tissue damages it and surrounding tissue.
In many cases the electrode array is introduced into electrically conductive tissue allowing for current spread, further decreasing the spacial resolution that can be achieved.
In contrast, optic stimulation can reliably achieve excitation of single cells or small cell populations. It does not require direct contact to the target tissue, reducing tissue damage. Finally electrical recordings of neural response in close proximity are not contaminated by the excitation stimulus. Although electrical stimulation suffers from the above mentioned drawbacks it is still the most well established and reliable method for nerve stimulation in patients.
Infrared stimulation is based on an infrared laser inducing a local temperature gradient inside the neuron. It does not require any modification of the cells prior to stimulation. The low energy laser does not cause damage to the tissue and elicits an artefact free stimulation. The exact mechanisms that lead to neuronal discharge are not known. However studies have shown that this phenomenon is most likely due to local photothermal processes.Thus the IR irradiation creates a temperature gradient confined to a small space which rapidly vanishes after irradiation ceases.
Optic stimulation in Neuro-Prosthetics
Electric stimulation has long been used for evoking nerve firing in neuronal prosthetics. However, spread of electrical current and generation of electric fields limit the spatial resolution that can be achieved. This limits the fidelity of the transmitted signal. In the case of auditory prostheses a maximum of around twenty electrodes is feasible, leaving the sound quality achieved far off the desired goal. A switch to optic based technology could achieve activation of smaller areas, increasing the amount of potentially perceived tones. Recent development in optic stimulation techniques promise ways to overcome those obstacles and improve prosthetic devices and the quality of life for patients.