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Optogenetics and Its Influence on the Clinical Neurosciences

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Optogenetics and Its Influence on the Clinical Neurosciences Journal, Vol. XXI, No. 1, 1-5, 2017 Cambridge Medicine Journal, 1-6, 2021 http://doi.dx.10.7244/cmj.2017.03.002http://doi.dx.10.7244/cmj.2020.12.002 Potential Applications of Three-dimensional Optogenetics and its influence on the clinical neurosciencesBioprinting in Regenerative Medicine Mateusz Gotowiec*1 Dominic Kwan 1UCL Medical School *Correspondence to: Mateusz Gotowiec, [email protected] In 1979, Francis Crick proposed an innovative solution: 1. Optogenetics – the basics of its action the use of light to control neurons [1]. His idea, combined with the prolonged effort of various scientists, resulted in Optogenetics is a unique domain in the complex of experi- a revolutionary technique – optogenetics - being chosen mental and therapeutic approaches in the field of neurobiol- DOI: 10.7244/cmj.2017.03.002 in 2010 as the "Method of the Year" across all branches ogy because it creates a possibility for the manipulation of of science and engineering [2, 3]. The first optogenetic normal and pathological neuronal networks, which cannot experiments commenced in 2005, however, it took several be achieved using any other techniques.Potential The underlying applications of three-dimensional years until this novel method began to be used in clinical idea behind this biological technique is the control of neu- neuroscience. In 2013, the European Brain Research Prize rons using light, primarily with photosensitive channels was awarded to Ernst Bamberg, Edward Boyden, Karl or pumps [6] which by changing ionic concentrationsbioprinting can in Regenerative Medicine Deisseroth, Peter Hegemann, Gero Miesenbock,¨ and Georg depolarise or hyperpolarise the whole cell. The aforemen- Nagel for their ‘invention and refinement of optogenetics’ tioned neuronal control is achieved through optogenetic ac- [4]. Using optogenetics, scientists could for the first time tuators (opsins) such as channelrhodopsin, halorhodopsin, Dominic Kwan examine the spatial, temporal, and cell-type resolution of and archaerhodopsin, while the recording of any changes the nervous system with such levels of precision. caused by these proteins can be done using optogenetic sen- This paper aims to highlight three major improvements sors of several types, including calcium or voltage change 09 March 2017 in neuroscience which occurred following optogenetics de- detectors. velopment. Firstly, a possibility was created for singular Opsins are a group of light-sensitive proteins (ion chan- cell specificity activation and the identification of particular nels or G-protein coupled receptors) which can interfere neuronal networks, which led to a better understanding of with cell membrane potential in response to light stimuli neurodegenerative processes in conditions such as Parkin- [6]. The main class of opsins used for the activation of neu- son’s disease [5]. Secondly, optogenetics introduced a new rons are type I opsins, also known as microbial. They are approach to treatment, underlining the need for a shift from preferentially employed as they1 allow Background a direct membrane By sectioneditor molecular-centric to pathway-centric concepts. Finally, it potential change, leading to an action potential transduc- began a substantial revolution in neuroscience, which is tion, thus having an immediate effect [7]. The second currently significantly influencing other branches of sci- class used, type II opsins, alsoIt cancalled be animal argued opsins, are that the concept of bioengineering began when Alexis Car- ence such as biotechnology and neurotechnology. a group of the G protein-coupled receptor (GPCR) super- rel and Charles Lindbergh published “The Culture of Organs” in 1938, which This literature review includes publications searchedCulture offamily. Organs As” opposedin 1938, to which type Idescribed opsins, they the act equipment indirectly using PubMedContents and Web of Science databases based on by changing the metabolic pathways in the neuron [8], and methods which made the in vitrodescribedmaintenance the of organs equipment and methods which made the in vitro maintenance a variety of keywords (‘optogenetics’, ‘opsins’, ‘opsin’, thus not provoking an instant response. The first step for 1 Background‘optogenetic’,1 ‘opto’). As the development is quite recent,possible.optogenetic The final chapter procedures of the is bookinjectingof organs mentions benign an viruses, possible. ‘ultimate most The final chapter of the book mentions an ‘ultimate goal’ 2 Clinical needonly2 sources between 2005 and 2019 have been usedgoal’ with whichcommonly suggests adeno-associated increasing thewhich viruses speed (AAV)of suggestshealing [9] containing wounds. increasing the speed of healing wounds. From its conception the majority having been published in the last decade.From Only itsopsin-coding conception genes in the into 1980s a selected to present group of day, neurons. scientists In this 3 Principles ofEnglish Application/Methods language literature of was Bioprinting used, including2 aand great medicalway, researchers the neural cells alike become havein been sensitive the investigating 1980s to light. to Proteins, the present ex- day, scientists and medical researchers alike have been 4 Discussion3portion of research papers showing optogenetic experimentciting prospectswhich act three-dimensional as switches, activate printing or disactivate offers to the the neurons field methodology, with lesser evidential value and a few review depending on light flashes whichinvestigating are sent in milliseconds the exciting prospects three-dimensional printing offers to the 4.1 Progress.............................3 of Medicine. Over the course of three decades, advances in papers focused on optogenetics applicability. through fiber optic cables.field Hence, of each Medicine. neuron can be Over the course of three decades, advances in this techno- 4.2 Challenges...........................3 this technologydepolarized have or led hyperpolarized to several famous using milestones; only the choice in the of process spawningwavelength the that term it receives. ‘bioprinting’. Inlogy this manner, have In contemporary the led manipula- to several famous milestones; in the process spawning the term 5 Conclusion4 medicine, bioprinting is beginning‘bioprinting’. to play a role in regener- In contemporary medicine, bioprinting is beginning to play a References4 ative medicine and clinical research by providing scientists with the ability to build tissue-engineeringrole in regenerativescaffolds, pros- medicine and clinical research by providing scientists wi- thetic limbs and even functioning kidneys.th the One ability of the earliest to build tissue-engineering scaffolds, prosthetic limbs and even 1. Background cases of bioprinting made international headlines in 1999, It can be argued that the concept of bioengineering began when the world’s first 3D printed collagen scaffold was used when Alexis Carrel and Charles Lindbergh published “The for bladder augmentations in dogs. Then in 2009, researchers 1 Optogenetics and its influence on the clinical neurosciences — 2/6 Figure 1. Chart showing basic optogenetic method. tion of singular neuronal activities becomes possible for light-dependent cellular apoptosis. Using optogenetically researchers. manipulated Bcl-2 family proteins, responsible for mito- chondrial outer membrane permeabilization (MOMP) [13], 1.1 Control over electrical and biochemical activ- they were able to recruit Bcl-2 proteins to the outer mito- ity chondrial membrane (OMM) with a light trigger. A mutant Optogenetics have not only allowed for the control of elec- cytosolic Bax protein was fused with a blue-light sensitive trical activity, but also of many biochemical processes. As Cry2 protein, creating the optoBcl-2, which was then di- stated previously, there are two types of opsins, which al- rected to the OMM using a light source. The subsequent low both electrical and biochemical manipulation of the light-dependent cellular collapse occurred in a cascade neurons. Most commonly, researchers focus on changing manner, with the mitochondrion-bound optoBcl-2 leading the electrical pattern of neuronal network activation, how- to pore formation in the OMM, the leakage of cytochrome ever, there is also a significant number of studies focused on c, the activation of the caspase pathway and eventually to manipulating the metabolic activity of cells. OptoXRs are a cell death [12]. Potentially, the control of cell metabolism new family of receptors sensitive to green light, made from through optoXRs, cell motility via optocofilin and apopto- a combination of GPCR membrane receptors (which nor- sis using optoBcl-2 may lead to future therapeutic innova- mally respond to many medicinal drugs) and the rhodopsin tions. domain [10]. When introduced into a mouse via a virus vector, optoXRs respond to light and successfully exercise 1.2 Precise study of neural circuits providing a certain biochemical transduction mechanisms. novel approach Furthermore, not only signal transduction can be in- Single-cell electrical activation is an important change fluenced by optogenetic protocols, but also cell motility. brought by optogenetics, as it has paved a new way for Cofilin is a member of the cofilin/actin-depolymerising analyzing specific neural circuits. Thanks to this develop- factor family, which acts on the actin filaments of the cy- ment, scientists were able to causally link neural circuits, toskeleton of a cell, regulating its motility. An optogenetic behavior, and function in diseases such as Parkinson’s
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