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The hallmark of optogenetics therefore is introduction of fast light-activated channels, pumps, and enzymes that allow temporally precise manipulation of electrical and biochemical events while maintaining cell-type resolution through the use of specific targeting mechanisms. Among the microbial opsins which can be used to investigate the function of neural systems are the [[channelrhodopsin]]s (ChR2, ChR1, VChR1, and SFOs) to excite neurons and [[anion-conducting channelrhodopsin]]s for light-induced inhibition. Indirectly light-controlled [[potassium channel]]s have recently been engineered to prevent action potential generation in neurons during blue light illumination.<ref>{{cite journal | vauthors = Beck S, Yu-Strzelczyk J, Pauls D, Constantin OM, Gee CE, Ehmann N, Kittel RJ, Nagel G, Gao S | display-authors = 6 | title = Synthetic Light-Activated Ion Channels for Optogenetic Activation and Inhibition | journal = Frontiers in Neuroscience | volume = 12 | pages = 643 | date = 2018 | pmid = 30333716 | pmc = 6176052 | doi = 10.3389/fnins.2018.00643 | doi-access = free }}</ref><ref>{{cite journal| vauthors = Sierra YA, Rost B, Oldani S, Schneider-Warme F, Seifert R, Schmitz D, Hegemann P |date=November 2018 |title=Potassium channel-based two component optogenetic tool for silencing of excitable cells|journal=Biophysical Journal|volume=114 |issue=3 |pages=668a |doi=10.1016/j.bpj.2017.11.3607 |bibcode=2018BpJ...114..668A|doi-access=free |hdl=21.11116/0000-0003-4AEF-E |hdl-access=free }}</ref> Light-driven ion pumps are also used to inhibit neuronal activity, e.g. [[halorhodopsin]] (NpHR),<ref name="Zhao 2008">{{cite journal | vauthors = Zhao S, Cunha C, Zhang F, Liu Q, Gloss B, Deisseroth K, Augustine GJ, Feng G | display-authors = 6 | title = Improved expression of halorhodopsin for light-induced silencing of neuronal activity | journal = Brain Cell Biology | volume = 36 | issue = 1–4 | pages = 141–154 | date = August 2008 | pmid = 18931914 | pmc = 3057022 | doi = 10.1007/s11068-008-9034-7 }}</ref> enhanced halorhodopsins (eNpHR2.0 and eNpHR3.0, see Figure 2),<ref name="Gradinaru 2008">{{cite journal | vauthors = Gradinaru V, Thompson KR, Deisseroth K | title = eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications | journal = Brain Cell Biology | volume = 36 | issue = 1–4 | pages = 129–139 | date = August 2008 | pmid = 18677566 | pmc = 2588488 | doi = 10.1007/s11068-008-9027-6 }}</ref> [[archaerhodopsin]] (Arch), fungal opsins (Mac) and enhanced bacteriorhodopsin (eBR).<ref name="Witten 2010">{{cite journal | vauthors = Witten IB, Lin SC, Brodsky M, Prakash R, Diester I, Anikeeva P, Gradinaru V, Ramakrishnan C, Deisseroth K | display-authors = 6 | title = Cholinergic interneurons control local circuit activity and cocaine conditioning | journal = Science | volume = 330 | issue = 6011 | pages = 1677–1681 | date = December 2010 | pmid = 21164015 | pmc = 3142356 | doi = 10.1126/science.1193771 | bibcode = 2010Sci...330.1677W }}</ref>
Optogenetic control of well-defined biochemical events within behaving mammals is now also possible. Building on prior work fusing vertebrate [[opsins]] to specific [[G-protein coupled receptors]]<ref>{{cite journal | vauthors = Kim JM, Hwa J, Garriga P, Reeves PJ, RajBhandary UL, Khorana HG | title = Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops | journal = Biochemistry | volume = 44 | issue = 7 | pages = 2284–2292 | date = February 2005 | pmid = 15709741 | doi = 10.1021/bi048328i }}</ref> a family of [[chimera (genetics)|chimeric]] single-component optogenetic tools was created that allowed researchers to manipulate within behaving mammals the concentration of defined intracellular messengers such as cAMP and IP3 in targeted cells.<ref name="Airan 2009">{{cite journal | vauthors = Airan RD, Thompson KR, Fenno LE, Bernstein H, Deisseroth K | title = Temporally precise in vivo control of intracellular signalling | journal = Nature | volume = 458 | issue = 7241 | pages = 1025–1029 | date = April 2009 | pmid = 19295515 | doi = 10.1038/nature07926 | s2cid = 4401796 | bibcode = 2009Natur.458.1025A }}</ref> Other biochemical approaches to optogenetics (crucially, with tools that displayed low activity in the dark) followed soon thereafter, when optical control over small GTPases and adenylyl cyclase was achieved in cultured cells using novel strategies from several different laboratories.<ref>{{cite journal | vauthors = Levskaya A, Weiner OD, Lim WA, Voigt CA | title = Spatiotemporal control of cell signalling using a light-switchable protein interaction | journal = Nature | volume = 461 | issue = 7266 | pages = 997–1001 | date = October 2009 | pmid = 19749742 | pmc = 2989900 | doi = 10.1038/nature08446 | bibcode = 2009Natur.461..997L }}</ref><ref>{{cite journal | vauthors = Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM | title = A genetically encoded photoactivatable Rac controls the motility of living cells | journal = Nature | volume = 461 | issue = 7260 | pages = 104–108 | date = September 2009 | pmid = 19693014 | pmc = 2766670 | doi = 10.1038/nature08241 | bibcode = 2009Natur.461..104W | author-link5 = Ilme Schlichting }}</ref><ref>{{cite journal | vauthors = Yazawa M, Sadaghiani AM, Hsueh B, Dolmetsch RE | title = Induction of protein-protein interactions in live cells using light | journal = Nature Biotechnology | volume = 27 | issue = 10 | pages = 941–945 | date = October 2009 | pmid = 19801976 | doi = 10.1038/nbt.1569 | s2cid = 205274357
'''Hardware for light application'''
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==Applications==
The field of optogenetics has furthered the fundamental scientific understanding of how specific cell types contribute to the function of biological tissues such as neural circuits ''in vivo''. On the clinical side, optogenetics-driven research has led to insights into restoring with light[https://www.sciencedirect.com/science/article/pii/S037859552300223X?via%3Dihub ],<ref>{{cite journal |last1=Azees |first1=Ajmal |title=Spread of activation and interaction between channels with multi-channel optogenetic stimulation in the mouse cochlea |journal=Hearing Research |date=December 2023 |volume=440 |doi=10.1016/j.heares.2023.108911 |pmid=37977051 |doi-access=free }}</ref> [[Parkinson's disease]]<ref name="Kravitz 2010">{{cite journal | vauthors = Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC | title = Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry | journal = Nature | volume = 466 | issue = 7306 | pages = 622–626 | date = July 2010 | pmid = 20613723 | pmc = 3552484 | doi = 10.1038/nature09159 | bibcode = 2010Natur.466..622K }}</ref><ref name="Gradinaru 2009">{{cite journal | vauthors = Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K | title = Optical deconstruction of parkinsonian neural circuitry | journal = Science | volume = 324 | issue = 5925 | pages = 354–359 | date = April 2009 | pmid = 19299587 | pmc = 6744370 | doi = 10.1126/science.1167093 | citeseerx = 10.1.1.368.668 | bibcode = 2009Sci...324..354G }}</ref> and other neurological and psychiatric disorders such as [[autism]], [[Schizophrenia]], [[drug abuse]], anxiety, and [[Major depressive disorder|depression]].<ref name="Witten 2010" /><ref name="Cardin 2009">{{cite journal | vauthors = Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI | display-authors = 6 | title = Driving fast-spiking cells induces gamma rhythm and controls sensory responses | journal = Nature | volume = 459 | issue = 7247 | pages = 663–667 | date = June 2009 | pmid = 19396156 | pmc = 3655711 | doi = 10.1038/nature08002 | bibcode = 2009Natur.459..663C }}</ref><ref name="Sohal 2009">{{cite journal | vauthors = Sohal VS, Zhang F, Yizhar O, Deisseroth K | title = Parvalbumin neurons and gamma rhythms enhance cortical circuit performance | journal = Nature | volume = 459 | issue = 7247 | pages = 698–702 | date = June 2009 | pmid = 19396159 | pmc = 3969859 | doi = 10.1038/nature07991 | bibcode = 2009Natur.459..698S }}</ref><ref name="Tsai 2009">{{cite journal | vauthors = Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K | title = Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning | journal = Science | volume = 324 | issue = 5930 | pages = 1080–1084 | date = May 2009 | pmid = 19389999 | pmc = 5262197 | doi = 10.1126/science.1168878 | bibcode = 2009Sci...324.1080T }}</ref> An experimental treatment for blindness involves a channel rhodopsin expressed in [[Retinal ganglion cell|ganglion cells]], stimulated with light patterns from engineered goggles.<ref>{{cite news | vauthors = Zimmer C |title=Scientists Partially Restored a Blind Man's Sight With New Gene Therapy |url=https://www.nytimes.com/2021/05/24/science/blindness-therapy-optogenetics.html |access-date=25 May 2021 |work=[[The New York Times]] |date=24 May 2021}}</ref><ref name=":13">{{cite journal | vauthors = Sahel JA, Boulanger-Scemama E, Pagot C, Arleo A, Galluppi F, Martel JN, Esposti SD, Delaux A, de Saint Aubert JB, de Montleau C, Gutman E, Audo I, Duebel J, Picaud S, Dalkara D, Blouin L, Taiel M, Roska B | display-authors = 6 | title = Partial recovery of visual function in a blind patient after optogenetic therapy | journal = Nature Medicine | volume = 27 | issue = 7 | pages = 1223–1229 | date = July 2021 | pmid = 34031601 | doi = 10.1038/s41591-021-01351-4 | doi-access = free }}</ref>
===Identification of particular neurons and networks===
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