Recently, Dr. Georg Nagel, the father of optogenetics, visited our Jin Kairui. It is said that this is a popular candidate for the Nobel Prize. Then the face of the eagerly ate melon asks: å•¥ is optogenetics, sounds So tall!
What is optogenetics?
Optogenetics is a rapidly developing multi-disciplinary bioengineering technology that integrates optics, software control, gene manipulation technology, and electrophysiology.
The main principle is to first use the gene manipulation technology to transfer light-sensitive genes (such as ChR2, eBR, NaHR3.0, Arch or OptoXR, etc.) into specific types of cells in the nervous system for expression of specific ion channels or GPCRs. The photo-sensing ion channel will selectively induce the passage of cations or anions under different wavelengths of light stimulation, thereby causing changes in the membrane potential on both sides of the cell membrane to achieve selective excitation or inhibition of the cells.
On the occasion of the tenth anniversary, Nature Methods magazine launched a special issue to review the top ten technologies that have had the most impact on biological research in the past decade, including optogenetics. It is no exaggeration to say that optogenetics has revolutionized neurology. Now, this technology has quickly become a standard tool in many laboratories. More and more people believe that optogenetics can not only clarify the disease mechanism, but also treat a variety of human diseases (such as diseases related to the retina).
Where is optogenetics good?
The benefits of using light to read and control neural activity are clear. This technique is non-invasive and targets at precise time and space. Multiple wavelengths and sites can be used simultaneously to report the presence or activity of a particular molecule. In signal reading, highly sensitive probes have been developed to detect synaptic release, intracellular calcium and membrane voltage. In terms of neuronal manipulation, a series of proteins that activate and inactivate neurons are identified and optimized.
Optogenetic technology has penetrated into every corner of neurology. Researchers not only use it to study the basic functions of the brain, but also explore the pathogenesis of disease in animal models. The optogenetic activators and repressors can be expressed in the same cell, which is particularly helpful for the establishment of causal relationships.
In the field of optogenetics, the development of new probes is crucial. The light-sensitive protein Channelrhodopsin and its mutants have been continuously modified to develop a C1V1 that is more conducive to two-photon excitation and a ReaChR that can be activated deep in the brain or through the skull. Recently, researchers have also engineered optogenetic inhibitors based on high-resolution crystal structures.
In addition, some inhibitory opsins have been identified from nature, including the widely used Arch15 and the recently discovered Jaws. In terms of signal reading, a new generation of calcium ion sensors (such as GCaMP6 and Twitch) and voltage sensors (QuasAr family) have emerged.
What is wrong with optogenetics?
Some critics believe that the standard usage of optogenetic activators is flawed. First, such levels of stimulation may make neuronal responses out of the physiological range, which is difficult to assess. In this case, the neural circuit will undergo unnatural changes, which will lead to incorrect physiological conclusions. This problem is not limited to the activator, and the suppressor may be beyond the normal range of action. Second, the expression and illumination of light-sensitive proteins are not uniform in the population of neurons, with the result that heterogeneity occurs in the magnitude and extent of optogenetic manipulation. In addition, large-scale light stimulation acts on the neuron population at the same time, which may cause non-physiological activity patterns in the loop. Finally, traditional optogenetic technology targets a specific genetic background of the neuronal population that can no longer selectively activate subpopulations. Now scientists have begun to address these issues.
In any case, biotechnology is changing with each passing day, and new research ideas are emerging one after another. I hope that we can keep up with the pace of the times and make great strides in the biological world!
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