INTRODUCTION:
What is Optogenetics? Have you ever heard about “光遺傳學 ”??? Optogenetics (光遺傳學) is the science of using light to stimulate certain responses from cells, groups of cells or organs within complex biological systems. Neuroscientists traditionally study the function of the brain by stimulating and recording the activity of single nerve cells with electrodes. The idea of using light to start or stop neurons in living animals was proposed some decades ago by the famous Nobel Prize–winning scientist, Francis Crick. The optogenetic method was pioneered in 2005 by Boyden and Karl Deisseroth at Stanford University.
However, what is optogenetics exactly? Optogenetics is the combination of genetics and optics to control well-defined events within specific cells of living tissue. It includes the discovery and insertion into cells of genes that confer light responsiveness; it also includes the associated technologies for delivering light deep into organisms as complex as freely moving
mammals, for targeting lightsensitivity to cells of interest, and for assessing specific readouts, or effects, of this optical control. Both precision in the length of the bursts of light and the ability to produce bursts of light with great speed are essential to the practice of optogenetics.
Optogenetics involves the use of light to provoke responses from certain proteins existing as part of complex biological systems. It can also involve the use of light to invoke responses from single cells, rather than groups of cells.
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Over the years, scientists have been trying hard to understand how our brains work. However, with limited technology, we human only knew a small part of this mystery. In 2002, some scientists discovered a protein that can cause green algae to move towards or away from light. They later found out that the protein (channelrhodopsin2 or ChR) is a light sensitive channel. Blue light causes the channel to open and enables ion to float in, which activate the nerve cell, while when given no light, the channel will be closed. They saw the potential of it and wondered if the protein can control the movement of the algae with light, if they get the protein into the nerve cell, they can control
the nerve activities in the brain. In August 2005, Ed Boyden and Feng Zhang have successfully tried the technology on mammal nerve system. The most famous example is the optogenetic were used to control the eyes’ behavior of a monkey. With inserting a certain ChR, when the blue light is on, the monkey eyed on the target faster than usual. In 2006 the word “optogentic” was even coined! This discovery has been a huge milestone for mankind. It has made us easier to understand our brain and even will be able to cure Parkinson’s disease or other metal illness. For your information, it hasn’t been used in a dark evil way like what you see in the movies, humans are not DOOMED, please don’t worry.
Living things responding to light?! So strange‌ Actually, living organisms with phototropic response are everywhere! For example plants, which usually grows towards the light. And of course we humans, where the light-sensitive cell on the retina of our eyes detect light. So you are now more familiar with phototropic response, but how does it work? In most cases, it involves light-sensitive proteins, which change their chemical structures when exposed to light. Let me introduce you a protein which plays a significant role in Optogenetics, the Channelrhodopsin It is a channel protein which opens to ion transportation when exposed to blue light So now we are using this kind of proteins to control biological process.
Let’s have a case study.
Mammals’ brains are made of neurons, or also called nerve cells. They send electrical pulses to control the body or when the organism is thinking.
We insert these light-sensitive proteins into the brain of a mouse. And when light hits the channel rhodopsin gene, the excited nerve cell carries out ion transportation and sends out electrical pulses, which in turn affects the behaviour of the mouse.
First of all, doctors are required to drill holes in people’s skulls to carry out the surgery. It also involves changing the DNA of brain cells unreliable and unpredictable, risky a optogenetics become more unfavorable. Fiber optics could pose the threat of infection and being uncomfortable and having to carry heavy batteries Optogenetics requires high tech work and specific knowledge to let the whole thing work. extremely expensive + May reserved for the wealthy ones but not ordinary people + Only a small number of people in the society will be able to enjoy this new technology, optogenetics is not the significantly great if it is not able to benefit the whole society. Moreover, to let optogenetics to become efficient, specific knowledge about the illnesses’ neural underpinning is needed. Unfortunately, this kind of specific knowledge is one of the most important missing puzzle pieces to let us solve major mental illness like depression. Therefore, we can conclude that without the knowledge about the illnesses’ neural underpinning, we cannot use this new technique. There are still quite a number of unsolved question in this field too.
What’s so good about optogenetics?
ll culture, Network analysis The optogenetic method provides new opportunities to analyze neural networks. This can be achieved by growing cultured nerve cells on micro or nano patterned substrates. Cells can be stimulated or silenced simply by a light-beam with up to now unknown spatial precision. Only for registration of the light evoked signals electrodes devices are necessary. Results from these experiments are expected to be used for theoretical work on neural nets.
Mapping of the brain and behavior Immediately after having demonstrated that ChR2 can be used for remote control of neurons, many laboratories started projects for the mapping of the brain in living animals. Excellent work by various groups shows, that the application of the optogenetic methods opens the door in the near future for more detailed studies, which have not been possible with the traditional electrical and optical methods. To name some examples; studies are possible on which certain areas of the brain are stimulated via light pipes. Results are obtained on the movement of whisker of rodents; on the olfactory system where light replaces the ligands, and on the movement of animals after stimulation of the motor cortex.
Gene therapy In the future gene therapy with the optogenetic tools appears possible. Transduction via Adeno Associated Viruses (AAV) has been performed successfully on the human eye to cure Lebers Congenital Amaurosis, by
transduction of cells in the human retina to replace the missing retinal isomerase. In analogy to this, AAV´s could be loaded with the microbial rhodopsins and could be used for gene therapy on the diseases listed below.
Recovery of vision Experiments on photoreceptor deficient mice have shown that light evokes potentials in the visual cortex after the transduction of the ON bipolar cells with ChR2 in the retina. This indicates that the retina of the animals regained photosensitivity, which is transmitted via the optic nerve to the brain. Trajectories of the movement of the animals in the dark and in the light show clearly an increased activity in the light as it is obtained for wild type animals. It is conceivable that such an approach might be possible for blind humans, suffering e.g. the dry or the wet maculardegeneration. However, in order to come to this point many biomedical, biophysical and technical hurdles have to be surmounted. This would be an alternative to the technology, which implants photosensitive chips in the human eye, which is far away from a satisfying treatment.
Parkinson disease, Epilepsy Besides the application of drugs Parkinson disease (PD) can be treated by Deep Brain Stimulation (DBS). The method consists of the stereotactic application of a metallic bipolar or quadrupole electrode to the nucleus subthalamicus within the brain. With help of the electrodes an oscillating electric field is applied stimulating the neuronal cells. With this approach spectacular results are obtained, which represent a substantial improvement compared to the drug therapy. Because of the geometry of the electrodes a precision of about one millimeter can be achieved. The extracellular stimulation by the electrodes induces not only the required depolarization of cells, but also partially a hyperpolarization, which inactivates cells with unwanted side effects. This means that parts of the target area are not under perfect control.
The optogenetic method is completely different. If successful this approach will lead to an improved treatment of PD: Virus induced transduction of cells with ChR2 allows the activation of the target structure in the brain via appropriate light sources without the side effects. As discussed above the advantages are the cell specificity, high temporal and spatial resolution in the micrometer range, which would open ways for the stimulation of substructures of the nucleus subthalamicus. The latter would give the chance to get a deeper understanding of the cause of this disease. With respect to Epilepsy similar arguments would hold, because here certain areas in the cortex are affected. One could speculate that optogenetics would attract focus also to other diseases including neuropsychiatric diseases. To summarize, optogenetics offers great opportunities to for basic research in the neurosciences, as already has been demonstrated by many laboratories worldwide. The biomedical applications, however, hold unpredictable challenges and risks.
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OPTOGENETICS, BIOLOGY, NERVE, CELLS, NEUROSCIENCE, LIGHT, MSCHOW, MSLEE, MRSIN, MRSLAM, MSWONG, MSLAU, CHEESE, MAKING, JOINTHECLUB, GENE
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BIOLOGY CLUB BULLETIN TEAM: 5A (6) Anson Lam 4I (7) Justin Leung 3B (21) Shum Wing Zi 3F (27) Wu Jenny 4B (7) Mak Siu Hin 4B (13) Chan Cheuk Ki Reference: http://www.youtube.com/watch?v=I64X7vHSHOE http://faculty.washington.edu/chudler/opto.html http://en.wikipedia.org/wiki/Optogenetics http://www.optogenetics.co.uk/index.html http://optogenetics.weebly.com/what-is-it1.html Wikipedia Optogenetics
A Light Switch for the Brain Derek Schweighart http://www.united-academics.org/magazine/mind-brain/new-mri-techniques-whatis-brain-mapping-and-how-does-it-work-optogenetics-mit/ Quoted from http://www.mpg.de/36227/bm06_Optogenetics-basetext.pdf