Recent Advances in Optogenetics (II)



  • Cell: optogenetics makes the mouse incarnate the cruel killer




There is a killer hidden in every mouse. Researchers have found areas of the brain that control predatory behavior and have succeeded in finding a way to control their switches. Dr. Ivan de Araujo from Yale University and colleagues found two nerves in the brain that control the hunting behavior of mice, one coordinated to chase the prey, and the other controlled the muscles of the neck and jaw. In the nucleus, the amygdala is the area of the human body involved in movements, feelings, and fears.


By modifying these nerves, they can activate these nerves by laser. This technique is called optogenetics, and the research team can, therefore, control the switching of these pathways at any time. When the laser is turned off, the mouse walks around the cage normally. Once the laser is turned on, the mouse will frantically attack anything on their way: live cockroaches, fake insects, or even branches or caps. They will pounce on the prey, grab the prey with their claws and bite repeatedly.


Later, the researchers tried to suppress the function of each group of nerves separately. When they suppressed the nerves responsible for hunting the prey, the rats chased slower, but still bite; in turn, if the nerves responsible for biting were suppressed, the rats would hunt and prey, but don’t bite.


  • Oncotarget: First use of optogenetics to control tumorigenesis




In a new study, researchers from Tufts University in the United States first demonstrated the use of light to control electrical signals between cells, prevent tumor formation, and normalize tumors after tumor formation. This study is the first to report the use of optogenetics to specifically manipulate bioelectrical signals to prevent oncogene-induced tumor formation and to cause oncogene-induced tumor regression. The relevant research results were published online in the Oncotarget journal and the title of the paper is “Use of genetically encoded, light-gated ion translocators to control tumorigenesis”.


Frogs are a good model organism for basic scientific research in cancer because frogs and mammalian tumors share many of the same characteristics, including rapid cell division, tissue destruction, increased vascular growth, invasiveness, and abnormal internal positive voltage cells. Almost all healthy cells maintain a larger negative voltage inside the cell than outside the cell; opening and closing the ion channel in the cell membrane can cause the voltage to become more positive (depolarization) or more negative (polarization). Under normal conditions, they can be detected using the abnormal bioelectrical signal characteristics of the tumor.


  • Neuron: Delete memory? The future may come true



Recently, in a research paper published in the journal Neuron, researchers from the Center for Neuroscience Research at the University of California, Davis, used light to successfully remove the special memory in the mouse brain. The research provides some ideas for how different parts of the brain work together to restore episodic memory.


Optogenetics is a new technology that uses light to study nerve cells. In recent years, it has been rapidly adopted by scientists as a standard method for brain function research. In the article, the researcher Kazumasa Tanaka applied the technology to the study of memory recovery. For 40 years, scientists assumed that restoring episodic memory (i.e., special events in special places) involves the cerebral cortex and coordinated activity between the hippocampus, the theory is to study the pattern of reactivation of brain activity involving the cerebral cortex and hippocampus during the recovery of episodic memory, so that the individual experiences those events again. If the hippocampus is damaged, the patient will lose the ten years of memory.


In the article, the researchers used genetically modified mice to study, when the mouse nerve cells were activated, they could all emit green fluorescence and express special proteins to promote the nerve cells to be light-closed. The researchers placed the mice in cages. In training, mice in the cage will experience electroshock. Normally, mice in a new environment will use the sense of smell to adapt to the environment, but when they are placed in a new environment after electroshock, they will be in a kind of fear reaction.


  • Nature: A new hope for optogenetic tools, the light-driven sodium channel KR2 structure is resolved




Japanese scientists published an academic article in Nature, which they analyzed the structure of the light-driven sodium channel protein KR2, creating the possibility for a new generation of optogenetic tools.


Many organisms can absorb the energy of light or the information of light, relying on a rhodopsin molecule. This molecule has a seven alpha helix transmembrane protein (opsin) linked to a retinal molecule via a covalent bond. According to the type of opsin, it can be divided into animal and microbial opsin. The rhodopsin function of microorganisms is different from that in animals, mainly as ion channels, ion transporters, photoreceptors or kinases. The rhodopsin of this microorganism is receiving more and more attention. This is because ion channel and ion pump type rhodopsin can be used for neural cell activity in many living organisms and has become a very powerful optogenetic tool in the field of neuroscience.


It is generally believed that the positively charged hydrogen ions of Schiff base are localized in the ion channels of all photoion pumps and are believed to prevent the passage of anions and neutral molecules. The analysis of the KR2 structure raises a new question as to how the ion pump transports sodium ions.


  • Neuron: Chicago scientists realize new breakthroughs in optogenetics



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With the deepening of research in the field of epigenetics by scientists in recent years, people began to hope to control the state of cells in vivo, especially neuronal cells, by means of in vitro stimulation. This field has broad application prospects, such as the treatment of genetic diseases such as macular degeneration. Based on this, disciplines such as optogenetics have been established. However, to date, researchers have had to genetically engineer neurons in order to achieve this goal. This has also greatly hindered the popularity of this technology.


Recent researchers from the University of Chicago and the University of Illinois at Chicago have made breakthroughs in this area. Researchers use the heat generated by far-infrared light to control the normal life activities of normal neuronal cells. Unlike previous practices that expressed light-sensitive proteins in normal neuronal cells, scientists chose to use gold nanoparticles to locate specific neurons. To solve the problem of gold nanoparticle specificity, the researchers connected a scorpion neurotoxin Ts1 to gold nanoparticles. Ts1 can target and recognize neuronal cells by recognizing sodium ion channels on the surface of neuronal cells. This is also the first time humans have achieved the goal of light-controlled neuron activity without modifying the genetic characteristics of neurons. However, this research is still in its early stages, and the researchers also said that Ts1 may be toxic to neuronal cells. This research work was published in the journal Neuron.


  • Nat Methods: Photosensitizers Control Cell Targeting




In a study published in the journal Nature Methods, researchers from Carnegie Mellon University redesigned a fluorescent probe for controlling cells in photosensitizers in optogenetics. It may also help to understand the role of specific cells and proteins in the development of disease, and also provide hope for targeted therapies for the later development of cancer or other diseases.


Optogenetics is the use of light to control the biological processes of the body. Researchers usually implement photo-controlled cell processes by reprogramming light-activated components into the organism’s genetic code. When these components are exposed to light, it will promote the partial function of some body tissues. Researchers have spent nearly 10 years developing fluorescent probes called fluorogen-activating proteins (FAPs), which are often used to monitor protein activity in real-time. The fluorophore-activated protein is usually expressed genetically in cells, and when it is contacted with a fluorescent dye called luciferin, the complex illuminates so that scientists can observe and track it.


Researcher Bruchez said that in order to develop labels for optogenetics, we have engineered fluorescent dyes to make them not only luminesce, but also to generate singlet oxygen (Singlet Oxygen), which is the toxic form of oxygen, when it binds to fluorophore-activating proteins and is exposed to light, targeting fluorophore-activating proteins and photosensitizer activation methods (FAP-TAPS) allows scientists to clearly see the labeled proteins while also selectivity inhibit the activity of these proteins.






Jennifer Brown, Reza Behnam, Luke Coddington et al. Expanding the Optogenetics Toolkit by Topological Inversion of Rhodopsins. Cell, Published Online: 18 October 2018, doi:10.1016/j.cell.2018.09.026.

Oleksandr Volkov, Kirill Kovalev, Vitaly Polovinkin et al. Structural insights into ion conduction by channelrhodopsin 2. Science, 24 Nov 2017, 358(6366):eaan8862, doi:10.1126/science.aan8862

Klaus Gerwert. Channelrhodopsin reveals its dark secrets. Science, 24 Nov 2017, 358(6366):1000-1001, doi:10.1126/science.aar2299

Perusini JN, Cajigas SA, Cohensedgh O. et al. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer’s disease mice. Hippocampus. 2017 Oct;27(10):1110-1122. doi: 10.1002/hipo.22756.

Han W, Tellez LA, Rangel MJ Jr. et al. Integrated Control of Predatory Hunting by the Central Nucleus of the Amygdala. Cell. 2017 Jan 12;168(1-2):311-324.e18. doi: 10.1016/j.cell.2016.12.027.

Chernet BT, Adams DS, Lobikin M, Levin M. Use of genetically encoded, light-gated ion translocators to control tumorigenesis. Oncotarget. 2016 Apr 12;7(15):19575-88. doi: 10.18632/oncotarget.8036.

Tanaka KZ, Pevzner A, Hamidi AB. et al. Cortical representations are reinstated by the hippocampus during memory retrieval. Neuron. 2014 Oct 22;84(2):347-54. doi: 10.1016/j.neuron.2014.09.037. Epub 2014 Oct 9.

Kato HE, Inoue K, Abe-Yoshizumi R. et al. Structural basis for Na(+) transport mechanism by a light-driven Na(+) pump. Nature. 2015 May 7;521(7550):48-53. doi: 10.1038/nature14322. Epub 2015 Apr 6.

Carvalho-de-Souza JL, Treger JS, Dang B. et al. Photosensitivity of neurons enabled by cell-targeted gold nanoparticles. Neuron. 2015 Apr 8;86(1):207-17. doi: 10.1016/j.neuron.2015.02.033.

He J, Wang Y, Missinato MA. et al. A genetically targetable near-infrared photosensitizer. Nat Methods. 2016 Mar;13(3):263-8. doi: 10.1038/nmeth.3735. Epub 2016 Jan 25.



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