Channelrhodopsin

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Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. [1] They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. [2] Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes (see optogenetics). Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions (ACRs, KCRs) have been cloned from other species of algae and protists.

Contents

History

Phototaxis and photoorientation of microalgae have been studied over more than a hundred years in many laboratories worldwide. In 1980, Ken Foster developed the first consistent theory about the functionality of algal eyes. [3] He also analyzed published action spectra and complemented blind cells with retinal and retinal analogues, which led to the conclusion that the photoreceptor for motility responses in Chlorophyceae is rhodopsin. [4]

Photocurrents of the Chlorophyceae Heamatococcus pluvialis and Chlamydomonas reinhardtii were studied over many years in the groups of Oleg Sineshchekov and Peter Hegemann. [5] [6] Based on action spectroscopy and simultaneous recordings of photocurrents and flagellar beating, it was determined that the photoreceptor currents and subsequent flagellar movements are mediated by rhodopsin and control phototaxis and photophobic responses. The extremely fast rise of the photoreceptor current after a brief light flash led to the conclusion that the rhodopsin and the channel are intimately linked in a protein complex, or even within one single protein. [7] [8]

The name "channelrhodopsin" was coined to highlight this unusual property, and the sequences were renamed accordingly. The nucleotide sequences of the rhodopsins now called channelrhodopsins ChR1 and ChR2 were finally uncovered in a large-scale EST sequencing project in C. reinhardtii. Independent submission of the same sequences to GenBank by three research groups generated confusion about their naming: The names cop-3 and cop-4 were used for initial submission by Hegemann's group; [9] csoA and csoB by Spudich's group; [2] and acop-1 and acop-2 by Takahashi's group. [10] Both sequences were found to function as single-component light-activated cation channels in a Xenopus oocytes and human kidney cells (HEK). [1] [11]

Their roles in generation of photoreceptor currents in algal cells were characterized by Oleg Sineshchekov, Kwang-Hwan Jung and John Spudich, [2] and Peter Berthold and Peter Hegemann. [12]

Structure

Crystal structure of channelrhodopsin. PDB 3ug9 3ug9.png
Crystal structure of channelrhodopsin. PDB 3ug9

In terms of structure, channelrhodopsins are retinylidene proteins. They are seven-transmembrane proteins like rhodopsin, and contain the light-isomerizable chromophore all- trans -retinal (an aldehyde derivative of vitamin A). The retinal chromophore is covalently linked to the rest of the protein through a protonated Schiff base. Whereas most 7-transmembrane proteins are G protein-coupled receptors that open other ion channels indirectly via second messengers (i.e., they are metabotropic), channelrhodopsins directly form ion channels (i.e., they are ionotropic). [11] This makes cellular depolarization extremely fast, robust, and useful for bioengineering and neuroscience applications, including photostimulation.

Function

Scheme of ChR2-RFP fusion construct ChR2scheme.png
Scheme of ChR2-RFP fusion construct

The natural ("wild-type") ChR2 absorbs blue light with an absorption and action spectrum maximum at 480 nm. [14] When the all-trans-retinal complex absorbs a photon, it induces a conformational change from all-trans to 13-cis-retinal. This change introduces a further one in the transmembrane protein, opening the pore to at least 6 Å. Within milliseconds, the retinal relaxes back to the all-trans form, closing the pore and stopping the flow of ions. [11] Most natural channelrhodopsins are nonspecific cation channels (CCRs), conducting H+, Na+, K+, and Ca2+ ions. Anion-conducting channelrhodopsins (ACRs) [15] and potassium-selective channelrhodpsins (HcKCR1, HcKCR2) [16] were structurally analyzed to understand their ion selectivity. [17] [18] ACRs and KCRs have been used to inhibit neuronal activity. Recently discovered viral channelrhodopsins (VCR1) are localized to the membrane of the endoplasmic reticulum and lead to calcium release when illuminated. [19]

Development as a molecular tool

In 2005, three groups sequentially established ChR2 as a tool for genetically targeted optical remote control (optogenetics) of neurons, neural circuits and behavior.

At first, Karl Deisseroth's lab demonstrated that ChR2 could be deployed to control mammalian neurons in vitro , achieving temporal precision on the order of milliseconds (both in terms of delay to spiking and in terms of temporal jitter). [20] Because all opsins require retinal as the light-sensing co-factor and it was unclear whether central mammalian nerve cells would contain sufficient retinal levels, but they do. It also showed, despite the small single-channel conductance, sufficient potency to drive mammalian neurons above action potential threshold. From this, channelrhodopsin became the first optogenetic tool, with which neural activity could be controlled with the temporal precision at which neurons operate (milliseconds). A second study was published later confirming the ability of ChR2 to control the activity of vertebrate neurons, at this time in the chick spinal cord. [21] This study was the first wherein ChR2 was expressed alongside an optical silencer, vertebrate rhodopsin-4 in this case, demonstrating for the first time that excitable cells could be activated and silenced using these two tools simultaneously, illuminating the tissue at different wavelengths.

It was demonstrated that ChR2, if expressed in specific neurons or muscle cells, can evoke predictable behaviors, i.e. can control the nervous system of an intact animal, in this case the invertebrate C. elegans . [22] This was the first using ChR2 to steer the behavior of an animal in an optogenetic experiment, rendering a genetically specified cell type subject to optical remote control. Although both aspects had been illustrated earlier that year by the group of Gero Miesenböck, deploying the indirectly light-gated ion channel P2X2, [23] it was henceforth microbial opsins like channelrhodopsin that dominated the field of genetically targeted remote control of excitable cells, due to the power, speed, targetability, ease of use, and temporal precision of direct optical activation, not requiring any external chemical compound such as caged ligands. [24]

To overcome its principal downsides — the small single-channel conductance (especially in steady-state), the limitation to one optimal excitation wavelength (~470 nm, blue) as well as the relatively long recovery time, not permitting controlled firing of neurons above 20–40 Hz — ChR2 has been optimized using genetic engineering. A point mutation H134R (exchanging the amino acid Histidine in position 134 of the native protein for an Arginine) resulted in increased steady-state conductance, as described in a 2005 paper that also established ChR2 as an optogenetic tool in C. elegans. [22] In 2009, Roger Tsien's lab optimized ChR2 for further increases in steady-state conductance and dramatically reduced desensitization by creating chimeras of ChR1 and ChR2 and mutating specific amino acids, yielding ChEF and ChIEF, which allowed the driving of trains of action potentials up to 100 Hz. [25] [26] In 2010, the groups of Hegemann and Deisseroth introduced an E123T mutation into native ChR2, yielding ChETA, which has faster on- and off-kinetics, permitting the control of individual action potentials at frequencies up to 200 Hz (in appropriate cell types). [27] [25]

The groups of Hegemann and Deisseroth also discovered that the introduction of the point mutation C128S makes the resulting ChR2-derivative a step-function tool: Once "switched on" by blue light, ChR2(C128S) stays in the open state until it is switched off by yellow light – a modification that deteriorates temporal precision, but increases light sensitivity by two orders of magnitude. [28] They also discovered and characterized VChR1 in the multicellular algae Volvox carteri. VChR1 produces only tiny photocurrents, but with an absorption spectrum that is red-shifted relative to ChR2. [29] Using parts of the ChR1 sequence, photocurrent amplitude was later improved to allow excitation of two neuronal populations at two distinct wavelengths. [30]

Deisseroth's group has pioneered many applications in live animals such as genetically targeted remote control in rodents in vivo , [31] the optogenetic induction of learning in rodents, [32] the experimental treatment of Parkinson's disease in rats, [33] [34] and the combination with fMRI (opto-fMRI). [35] Other labs have pioneered the combination of ChR2 stimulation with calcium imaging for all-optical experiments, [36] mapping of long-range [37] and local [38] neural circuits, ChR2 expression from a transgenic locus – directly [39] or in the Cre-lox conditional paradigm [38] – as well as the two-photon excitation of ChR2, permitting the activation of individual cells. [40] [41] [42]

In March 2013, the Brain Prize (Grete Lundbeck European Brain Research Prize) was jointly awarded to Bamberg, Boyden, Deisseroth, Hegemann, Miesenböck, and Nagel for "their invention and refinement of optogenetics". [43] The same year, Hegemann and Nagel received the Louis-Jeantet Prize for Medicine for "the discovery of channelrhodopsin". In 2015, Boyden and Deisseroth received the Breakthrough Prize in Life Sciences and in 2020, Miesenböck, Hegemann and Nagel received the Shaw prize in Life Science and Medicine for the development of optogenetics.

Designer-channelrhodopsins

Channelrhodopsins are key tools in optogenetics. The C-terminal end of Channelrhodopsin-2 extends into the intracellular space and can be replaced by fluorescent proteins without affecting channel function. This kind of fusion construct can be useful to visualize the morphology of ChR2 expressing cells, i.e. simultaneously indicate which cells are tagged with FP and allow the activity to be controlled by the channelrhodopsin. [20] [36] Point mutations close to the retinal binding pocket have been shown to affect the biophysical properties of the channelrhodopsin, resulting in a variety of different tools.

Kinetics

Closing of the channel after optical activation can be substantially delayed by mutating the protein residues C128 or D156. This modification results in super-sensitive channelrhodopsins that can be opened by a blue light pulse and closed by a green or yellow light pulse (Step-function opsins). [28] [44] [30] Mutating the E123 residue accelerates channel kinetics (ChETA), and the resulting ChR2 mutants have been used to spike neurons at up to 200 Hz. [27] In general, channelrhodopsins with slow kinetics are more light-sensitive on the population level, as open channels accumulate over time even at low light levels.

Photocurrent amplitude

H134R and T159C mutants display increased photocurrents, and a combination of T159 and E123 (ET/TC) has slightly larger photocurrents and slightly faster kinetics than wild-type ChR2. [45] ChIEF, a chimera and point mutant of ChR1 and ChR2, demonstrates large photocurrents, little desensitization and kinetics similar to wild-type ChR2. [25] Variants with extended open time (ChR2-XXL) produce extremely large photocurrents and are very light sensitive on the population level. [46]

Wavelength

Chimeric channelrhodopsins have been developed by combining transmembrane helices from ChR1 and VChR1, leading to the development of ChRs with red spectral shifts (such as C1V1 and ReaChR). [30] [47] ReaChR has improved membrane trafficking and strong expression in mammalian cells, and has been used for minimally invasive, transcranial activation of brainstem motoneurons. Searches for homologous sequences in other organisms has yielded spectrally improved and stronger red-shifted channelrhodpsins (Chrimson). [48] In combination with ChR2, these yellow/red light-sensitive channelrhodopsins allow controlling two populations of neurons independently with light pulses of different colors. [49] [50]

A blue-shifted channelrhodopsin has been discovered in the alga Scherffelia dubia. After some engineering to improve membrane trafficking and speed, the resulting tool (CheRiff) produced large photocurrents at 460 nm excitation. [51] It has been combined with the Genetically Encoded Calcium Indicator jRCaMP1b [52] in an all-optical system called the OptoCaMP. [53]

Ion selectivity

Most channelrhodopsins are unspecific cation channels. When expressed in neurons, they conduct mostly Na+ ions and are therefore depolarizing (excitatory). Variants with moderate to high calcium permeability have been engineered (CatCh, CapChRs). [54] [55] K+-specific channelrhodopsins (KCRs, WiChR) were recently discovered in various protists. [56] [57] When expressed in neurons, potassium-selective channelrhodopsins hyperpolarize the membrane upon illumination, preventing spike generation (inhibitory).

Mutating E90 to the positively charged amino acid arginine turns channelrhodopsin from an unspecific cation channel into a chloride-conducting channel (ChloC). [58] The selectivity for Cl- was further improved by replacing negatively charged residues in the channel pore, making the reversal potential more negative. [59] [60] Anion-conducting channelrhodopsins (iChloC, iC++, GtACR) inhibit neuronal spiking in cell culture and in intact animals when illuminated with blue light. Calcium-selective channelrhodopsins have been engineered to activate calcium-dependent enzymes in cells. [61]

Applications

Channelrhodopsins can be readily expressed in excitable cells such as neurons using a variety of transfection techniques (viral transfection, electroporation, gene gun) or transgenic animals. The light-absorbing pigment retinal is present in most cells (of vertebrates) as Vitamin A, making it possible to photostimulate neurons without adding any chemical compounds. Before the discovery of channelrhodopsins, neuroscientists were limited to recording the activity of neurons in the brain and correlate this activity with behavior. This is not sufficient to prove that the recorded neural activity actually caused that behavior. Controlling networks of genetically modified cells with light, an emerging field known as Optogenetics., allows researchers now to explore the causal link between activity in a specific group of neurons and mental events, e.g. decision making. Optical control of behavior has been demonstrated in nematodes, fruit flies, zebrafish, and mice. [62] [63] Recently, chloride-conducting channelrhodopsins have been engineered and were also found in nature. [15] [58] These tools can be used to silence neurons in cell culture and in live animals by shunting inhibition. [59] [60]

Using multiple colors of light expands the possibilities of optogenetic experiments. The blue-light sensitive ChR2 and the yellow light-activated chloride pump halorhodopsin together enable multiple-color optical activation and silencing of neural activity. [64] [65] Another interesting pair is the blue-light sensitive chloride channel GtACR2 [66] and the red-light sensitive cation channel Chrimson [67] which have been combined in a single protein (BiPOLES) for bidirectional control of membrane potential. [68]

Using fluorescently labeled ChR2, light-stimulated axons and synapses can be identified. [36] This is useful to study the molecular events during the induction of synaptic plasticity. [69] [70] Transfected cultured neuronal networks can be stimulated to perform some desired behaviors for applications in robotics and control. [71] ChR2 has also been used to map long-range connections from one side of the brain to the other, and to map the spatial location of inputs on the dendritic tree of individual neurons. [37] [72]

In 2006, it was reported that transfection with Channelrhodopsin could restore eyesight to blind mice. [73]

Neurons can tolerate ChR expression for a long time, and several laboratories are testing optogenetic stimulation to solve medical needs. In blind mice, visual function can be partially restored by expressing ChR2 in inner retinal cells. [74] [75] In 2021, the red-light sensitive ChR ChrimsonR was virally delivered to the eyes of a human patient suffering from retinal degeneration (retinitis pigmentosa), leading to partial recovery of his vision. [76] [77] Optical cochlear implants have been shown to work well in animal experiments and are currently undergoing clinical trials. [78] [79] [80] In the future, ChRs may find even more medical applications, e.g. for deep-brain stimulation of Parkinson patients or to control certain forms of epilepsy.

Related Research Articles

<span class="mw-page-title-main">Rhodopsin</span> Light-sensitive receptor protein

Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction in rods. Rhodopsin mediates dim light vision and thus is extremely sensitive to light. When rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, after which the rods are more sensitive. Defects in the rhodopsin gene cause eye diseases such as retinitis pigmentosa and congenital stationary night blindness.

<span class="mw-page-title-main">Behavioral neuroscience</span> Field of study

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology, is the application of the principles of biology to the study of physiological, genetic, and developmental mechanisms of behavior in humans and other animals.

<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

<span class="mw-page-title-main">Opsin</span> Class of light-sensitive proteins

Animal opsins are G-protein-coupled receptors and a group of proteins made light-sensitive via a chromophore, typically retinal. When bound to retinal, opsins become retinylidene proteins, but are usually still called opsins regardless. Most prominently, they are found in photoreceptor cells of the retina. Five classical groups of opsins are involved in vision, mediating the conversion of a photon of light into an electrochemical signal, the first step in the visual transduction cascade. Another opsin found in the mammalian retina, melanopsin, is involved in circadian rhythms and pupillary reflex but not in vision. Humans have in total nine opsins. Beside vision and light perception, opsins may also sense temperature, sound, or chemicals.

<span class="mw-page-title-main">Photostimulation</span>

Photostimulation is the use of light to artificially activate biological compounds, cells, tissues, or even whole organisms. Photostimulation can be used to noninvasively probe various relationships between different biological processes, using only light. In the long run, photostimulation has the potential for use in different types of therapy, such as migraine headache. Additionally, photostimulation may be used for the mapping of neuronal connections between different areas of the brain by “uncaging” signaling biomolecules with light. Therapy with photostimulation has been called light therapy, phototherapy, or photobiomodulation.

<span class="mw-page-title-main">Halorhodopsin</span> Family of transmembrane proteins


Halorhodopsin is a seven-transmembrane retinylidene protein from microbial rhodopsin family. It is a chloride-specific light-activated ion pump found in archaea known as halobacteria. It is activated by green light wavelengths of approximately 578nm. Halorhodopsin also shares sequence similarity to channelrhodopsin, a light-gated ion channel.

Retinylidene proteins, or rhodopsins in a broad sense, are proteins that use retinal as a chromophore for light reception. They are the molecular basis for a variety of light-sensing systems from phototaxis in flagellates to eyesight in animals. Retinylidene proteins include all forms of opsin and rhodopsin. While rhodopsin in the narrow sense refers to a dim-light visual pigment found in vertebrates, usually on rod cells, rhodopsin in the broad sense refers to any molecule consisting of an opsin and a retinal chromophore in the ground state. When activated by light, the chromophore is isomerized, at which point the molecule as a whole is no longer rhodopsin, but a related molecule such as metarhodopsin. However, it remains a retinylidene protein. The chromophore then separates from the opsin, at which point the bare opsin is a retinylidene protein. Thus, the molecule remains a retinylidene protein throughout the phototransduction cycle.

Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion channels include voltage-gated ion channels, ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels have been synthesized in the laboratory for study, although two naturally occurring examples, channelrhodopsin and anion-conducting channelrhodopsin, are currently known. Photoreceptor proteins, which act in a similar manner to light-gated ion channels, are generally classified instead as G protein-coupled receptors.

<span class="mw-page-title-main">Gero Miesenböck</span>

Gero Andreas Miesenböck is an Austrian scientist. He is currently Waynflete Professor of Physiology and Director of the Centre for Neural Circuits and Behaviour (CNCB) at the University of Oxford and a fellow of Magdalen College, Oxford.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.

<span class="mw-page-title-main">Karl Deisseroth</span> American optogeneticist (born 1971)

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

<span class="mw-page-title-main">Peter Hegemann</span> German biophysicist

Peter Hegemann is a Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at the Department of Biology, Faculty of Life Sciences, Humboldt University of Berlin, Germany. He is known for his discovery of channelrhodopsin, a type of ion channels regulated by light, thereby serving as a light sensor. This created the field of optogenetics, a technique that controls the activities of specific neurons by applying light. He has received numerous accolades, including the Rumford Prize, the Shaw Prize in Life Science and Medicine, and the Albert Lasker Award for Basic Medical Research.

<span class="mw-page-title-main">Microbial rhodopsin</span> Retinal-binding proteins

Microbial rhodopsins, also known as bacterial rhodopsins, are retinal-binding proteins that provide light-dependent ion transport and sensory functions in halophilic and other bacteria. They are integral membrane proteins with seven transmembrane helices, the last of which contains the attachment point for retinal.

<span class="mw-page-title-main">Anion-conducting channelrhodopsin</span> Class of light-gated ion channels

Anion-conducting channelrhodopsins are light-gated ion channels that open in response to light and let negatively charged ions enter a cell. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins are used as tools to manipulate brain activity in mice, fruit flies and other model organisms (Optogenetics). Neurons expressing anion-conducting channelrhodopsins are silenced when illuminated with light, an effect that has been used to investigate information processing in the brain. For example, suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker. Studying how the behavior of an animal changes when specific neurons are silenced allows scientists to determine the role of these neurons in the complex circuits controlling behavior.

<span class="mw-page-title-main">Archaerhodopsin</span> Family of archaea

Archaerhodopsin proteins are a family of retinal-containing photoreceptors found in the archaea genera Halobacterium and Halorubrum. Like the homologous bacteriorhodopsin (bR) protein, archaerhodopsins harvest energy from sunlight to pump H+ ions out of the cell, establishing a proton motive force that is used for ATP synthesis. They have some structural similarities to the mammalian G protein-coupled receptor protein rhodopsin, but are not true homologs.

Zhuo-Hua Pan is a Chinese-American neuroscientist, known for his foundational contributions to optogenetics. He is the Edward T. and Ellen K. Dryer Endowed Professor of Ophthalmology at Wayne State University, and Scientific Director of the Ligon Research Center of Vision at the university's Kresge Eye Institute.

<span class="mw-page-title-main">Georg Nagel</span>

Georg Nagel is a biophysicist and professor at the Department for Neurophysiology at the University of Würzburg in Germany. His research is focused on microbial photoreceptors and the development of optogenetic tools.

Ernst Bamberg is a German biophysicist and director emeritus of the Department of Biophysical Chemistry at the Max Planck Institute of Biophysics.

<span class="mw-page-title-main">Photoactivated adenylyl cyclase</span>

Photoactivated adenylyl cyclase (PAC) is a protein consisting of an adenylyl cyclase enzyme domain directly linked to a BLUF type light sensor domain. When illuminated with blue light, the enzyme domain becomes active and converts ATP to cAMP, an important second messenger in many cells. In the unicellular flagellate Euglena gracilis, PACα and PACβ (euPACs) serve as a photoreceptor complex that senses light for photophobic responses and phototaxis. Small but potent PACs were identified in the genome of the bacteria Beggiatoa (bPAC) and Oscillatoria acuminata (OaPAC). While natural bPAC has some enzymatic activity in the absence of light, variants with no dark activity have been engineered (PACmn).

Lisa Gunaydin is an American neuroscientist and assistant professor at the Weill Institute for Neurosciences at the University of California San Francisco. Gunaydin helped discover optogenetics in the lab of Karl Deisseroth and now uses this technique in combination with neural and behavioral recordings to probe the neural circuits underlying emotional behaviors.

References

  1. 1 2 Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM, Bamberg E, et al. (June 2002). "Channelrhodopsin-1: a light-gated proton channel in green algae". Science. 296 (5577): 2395–2398. Bibcode:2002Sci...296.2395N. doi:10.1126/science.1072068. PMID   12089443. S2CID   206506942.
  2. 1 2 3 Sineshchekov OA, Jung KH, Spudich JL (June 2002). "Two rhodopsins mediate phototaxis to low- and high-intensity light in Chlamydomonas reinhardtii". Proceedings of the National Academy of Sciences of the United States of America. 99 (13): 8689–8694. doi: 10.1073/pnas.122243399 . PMC   124360 . PMID   12060707.
  3. ↑ Foster KW, Smyth RD (December 1980). "Light Antennas in phototactic algae". Microbiological Reviews. 44 (4): 572–630. doi:10.1128/mr.44.4.572-630.1980. PMC   373196 . PMID   7010112.
  4. ↑ Foster KW, Saranak J, Patel N, Zarilli G, Okabe M, Kline T, et al. (October 1984). "A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas". Nature. 311 (5988): 756–759. Bibcode:1984Natur.311..756F. doi:10.1038/311756a0. PMID   6493336. S2CID   4263301.
  5. ↑ Litvin FF, Sineshchekov OA, Sineshchekov VA (February 1978). "Photoreceptor electric potential in the phototaxis of the alga Haematococcus pluvialis". Nature. 271 (5644): 476–478. Bibcode:1978Natur.271..476L. doi:10.1038/271476a0. PMID   628427. S2CID   4165365.
  6. ↑ Harz H, Hegemann P (June 1991). "Rhodopsin-regulated calcium currents in Chlamydomonas". Nature. 351 (6326): 489–491. Bibcode:1991Natur.351..489H. doi:10.1038/351489a0. S2CID   4309593.
  7. ↑ Holland EM, Braun FJ, Nonnengässer C, Harz H, Hegemann P (February 1996). "The nature of rhodopsin-triggered photocurrents in Chlamydomonas. I. Kinetics and influence of divalent ions". Biophysical Journal. 70 (2): 924–931. Bibcode:1996BpJ....70..924H. doi:10.1016/S0006-3495(96)79635-2. PMC   1224992 . PMID   8789109.
  8. ↑ Braun FJ, Hegemann P (March 1999). "Two light-activated conductances in the eye of the green alga Volvox carteri". Biophysical Journal. 76 (3): 1668–1678. Bibcode:1999BpJ....76.1668B. doi:10.1016/S0006-3495(99)77326-1. PMC   1300143 . PMID   10049347.
  9. ↑ Kateriya, S. Fuhrmann, M. Hegemann, P.: Direct Submission: Chlamydomonas reinhardtii retinal binding protein (cop4) gene; GenBank accession number AF461397
  10. ↑ Suzuki T, Yamasaki K, Fujita S, Oda K, Iseki M, Yoshida K, et al. (February 2003). "Archaeal-type rhodopsins in Chlamydomonas: model structure and intracellular localization". Biochemical and Biophysical Research Communications. 301 (3): 711–717. doi:10.1016/S0006-291X(02)03079-6. PMID   12565839.
  11. 1 2 3 Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P, et al. (November 2003). "Channelrhodopsin-2, a directly light-gated cation-selective membrane channel". Proceedings of the National Academy of Sciences of the United States of America. 100 (24): 13940–13945. Bibcode:2003PNAS..10013940N. doi: 10.1073/pnas.1936192100 . PMC   283525 . PMID   14615590.
  12. ↑ Berthold P, Tsunoda SP, Ernst OP, Mages W, Gradmann D, Hegemann P (June 2008). "Channelrhodopsin-1 initiates phototaxis and photophobic responses in chlamydomonas by immediate light-induced depolarization". The Plant Cell. 20 (6): 1665–1677. doi:10.1105/tpc.108.057919. PMC   2483371 . PMID   18552201.
  13. ↑ Kato HE, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T, Hirata K, et al. (January 2012). "Crystal structure of the channelrhodopsin light-gated cation channel". Nature. 482 (7385): 369–374. Bibcode:2012Natur.482..369K. doi:10.1038/nature10870. PMC   4160518 . PMID   22266941.
  14. ↑ Bamann C, Kirsch T, Nagel G, Bamberg E (January 2008). "Spectral characteristics of the photocycle of channelrhodopsin-2 and its implication for channel function". Journal of Molecular Biology. 375 (3): 686–694. doi:10.1016/j.jmb.2007.10.072. PMID   18037436.
  15. 1 2 Govorunova EG, Sineshchekov OA, Janz R, Liu X, Spudich JL (August 2015). "NEUROSCIENCE. Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics". Science. 349 (6248): 647–650. Bibcode:2015Sci...349..647G. doi:10.1126/science.aaa7484. PMC   4764398 . PMID   26113638.
  16. ↑ Govorunova EG, Gou Y, Sineshchekov OA, Li H, Lu X, Wang Y, et al. (July 2022). "Kalium channelrhodopsins are natural light-gated potassium channels that mediate optogenetic inhibition". Nature Neuroscience. 25 (7): 967–974. doi:10.1038/s41593-022-01094-6. PMC   9854242 . PMID   35726059. S2CID   249886382.
  17. ↑ Kim YS, Kato HE, Yamashita K, Ito S, Inoue K, Ramakrishnan C, et al. (September 2018). "Crystal structure of the natural anion-conducting channelrhodopsin GtACR1". Nature. 561 (7723): 343–348. Bibcode:2018Natur.561..343K. doi:10.1038/s41586-018-0511-6. PMC   6340299 . PMID   30158696.
  18. ↑ Tajima S, Kim YS, Fukuda M, Byrne EF, Wang PY, Paggi JM, et al. (2022-10-31). "Structural basis for ion selectivity in potassium-selective channelrhodopsins" (PDF). bioRxiv. doi:10.1101/2022.10.30.514430. S2CID   253259023.
  19. ↑ Eria-Oliveira AS, Folacci M, Chassot AA, Fedou S, Thézé N, Zabelskii D, et al. (2024-01-02). "Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins". Nature Communications. 15 (1): 65. Bibcode:2024NatCo..15...65E. doi:10.1038/s41467-023-44548-6. ISSN   2041-1723. PMC   10761956 . PMID   38167346.
  20. 1 2 Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (September 2005). "Millisecond-timescale, genetically targeted optical control of neural activity". Nature Neuroscience. 8 (9): 1263–1268. doi:10.1038/nn1525. PMID   16116447. S2CID   6809511.
  21. ↑ Li X, Gutierrez DV, Hanson MG, Han J, Mark MD, Chiel H, et al. (December 2005). "Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin". Proceedings of the National Academy of Sciences of the United States of America. 102 (49): 17816–17821. Bibcode:2005PNAS..10217816L. doi: 10.1073/pnas.0509030102 . PMC   1292990 . PMID   16306259.
  22. 1 2 Nagel G, Brauner M, Liewald JF, Adeishvili N, Bamberg E, Gottschalk A (December 2005). "Light activation of channelrhodopsin-2 in excitable cells of Caenorhabditis elegans triggers rapid behavioral responses". Current Biology. 15 (24): 2279–2284. Bibcode:2005CBio...15.2279N. doi: 10.1016/j.cub.2005.11.032 . PMID   16360690.
  23. ↑ Lima SQ, Miesenböck G (April 2005). "Remote control of behavior through genetically targeted photostimulation of neurons". Cell. 121 (1): 141–152. doi: 10.1016/j.cell.2005.02.004 . PMID   15820685.
  24. ↑ Zhang F, Wang LP, Boyden ES, Deisseroth K (October 2006). "Channelrhodopsin-2 and optical control of excitable cells". Nature Methods. 3 (10): 785–792. doi:10.1038/nmeth936. PMID   16990810. S2CID   15096826.
  25. 1 2 3 Lin JY (January 2011). "A user's guide to channelrhodopsin variants: features, limitations and future developments". Experimental Physiology. 96 (1): 19–25. doi:10.1113/expphysiol.2009.051961. PMC   2995811 . PMID   20621963.
  26. ↑ Lin JY, Lin MZ, Steinbach P, Tsien RY (March 2009). "Characterization of engineered channelrhodopsin variants with improved properties and kinetics". Biophysical Journal. 96 (5): 1803–1814. Bibcode:2009BpJ....96.1803L. doi:10.1016/j.bpj.2008.11.034. PMC   2717302 . PMID   19254539.
  27. 1 2 Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P (March 2010). "Ultrafast optogenetic control". Nature Neuroscience. 13 (3): 387–392. doi:10.1038/nn.2495. PMID   20081849. S2CID   7457755.
  28. 1 2 Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K (February 2009). "Bi-stable neural state switches". Nature Neuroscience. 12 (2): 229–234. doi:10.1038/nn.2247. PMID   19079251. S2CID   15125498.
  29. ↑ Zhang F, Prigge M, Beyrière F, Tsunoda SP, Mattis J, Yizhar O, et al. (June 2008). "Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri". Nature Neuroscience. 11 (6): 631–633. doi:10.1038/nn.2120. PMC   2692303 . PMID   18432196.
  30. 1 2 3 Yizhar O, Fenno LE, Prigge M, Schneider F, Davidson TJ, O'Shea DJ, et al. (July 2011). "Neocortical excitation/inhibition balance in information processing and social dysfunction". Nature. 477 (7363): 171–178. Bibcode:2011Natur.477..171Y. doi:10.1038/nature10360. PMC   4155501 . PMID   21796121.
  31. ↑ Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L (November 2007). "Neural substrates of awakening probed with optogenetic control of hypocretin neurons". Nature. 450 (7168): 420–424. Bibcode:2007Natur.450..420A. doi:10.1038/nature06310. PMC   6744371 . PMID   17943086.
  32. ↑ Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, et al. (May 2009). "Phasic firing in dopaminergic neurons is sufficient for behavioral conditioning". Science. 324 (5930): 1080–1084. Bibcode:2009Sci...324.1080T. doi:10.1126/science.1168878. PMC   5262197 . PMID   19389999.
  33. ↑ Gradinaru V, Mogri M, Thompson KR, Henderson JM, Deisseroth K (April 2009). "Optical deconstruction of parkinsonian neural circuitry". Science. 324 (5925): 354–359. Bibcode:2009Sci...324..354G. CiteSeerX   10.1.1.368.668 . doi:10.1126/science.1167093. PMC   6744370 . PMID   19299587.
  34. ↑ Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, et al. (July 2010). "Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry". Nature. 466 (7306): 622–626. Bibcode:2010Natur.466..622K. doi:10.1038/nature09159. PMC   3552484 . PMID   20613723.
  35. ↑ Lee JH, Durand R, Gradinaru V, Zhang F, Goshen I, Kim DS, et al. (June 2010). "Global and local fMRI signals driven by neurons defined optogenetically by type and wiring". Nature. 465 (7299): 788–792. Bibcode:2010Natur.465..788L. doi:10.1038/nature09108. PMC   3177305 . PMID   20473285.
  36. 1 2 3 Zhang YP, Oertner TG (February 2007). "Optical induction of synaptic plasticity using a light-sensitive channel". Nature Methods. 4 (2): 139–141. doi:10.1038/nmeth988. PMID   17195846. S2CID   17721823.
  37. 1 2 Petreanu L, Huber D, Sobczyk A, Svoboda K (May 2007). "Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections". Nature Neuroscience. 10 (5): 663–668. doi:10.1038/nn1891. PMID   17435752. S2CID   14275254.
  38. 1 2 Kätzel D, Zemelman BV, Buetfering C, Wölfel M, Miesenböck G (January 2011). "The columnar and laminar organization of inhibitory connections to neocortical excitatory cells". Nature Neuroscience. 14 (1): 100–107. doi:10.1038/nn.2687. PMC   3011044 . PMID   21076426.
  39. ↑ Wang H, Peca J, Matsuzaki M, Matsuzaki K, Noguchi J, Qiu L, et al. (May 2007). "High-speed mapping of synaptic connectivity using photostimulation in Channelrhodopsin-2 transgenic mice". Proceedings of the National Academy of Sciences of the United States of America. 104 (19): 8143–8148. Bibcode:2007PNAS..104.8143W. doi: 10.1073/pnas.0700384104 . PMC   1876585 . PMID   17483470.
  40. ↑ Mohanty SK, Reinscheid RK, Liu X, Okamura N, Krasieva TB, Berns MW (October 2008). "In-depth activation of channelrhodopsin 2-sensitized excitable cells with high spatial resolution using two-photon excitation with a near-infrared laser microbeam". Biophysical Journal. 95 (8): 3916–3926. Bibcode:2008BpJ....95.3916M. doi:10.1529/biophysj.108.130187. PMC   2553121 . PMID   18621808.
  41. ↑ Rickgauer JP, Tank DW (September 2009). "Two-photon excitation of channelrhodopsin-2 at saturation". Proceedings of the National Academy of Sciences of the United States of America. 106 (35): 15025–15030. Bibcode:2009PNAS..10615025R. doi: 10.1073/pnas.0907084106 . PMC   2736443 . PMID   19706471.
  42. ↑ Andrasfalvy BK, Zemelman BV, Tang J, Vaziri A (June 2010). "Two-photon single-cell optogenetic control of neuronal activity by sculpted light". Proceedings of the National Academy of Sciences of the United States of America. 107 (26): 11981–11986. Bibcode:2010PNAS..10711981A. doi: 10.1073/pnas.1006620107 . PMC   2900666 . PMID   20543137.
  43. ↑ Reiner A, Isacoff EY (October 2013). "The Brain Prize 2013: the optogenetics revolution". Trends in Neurosciences. 36 (10): 557–560. doi:10.1016/j.tins.2013.08.005. PMID   24054067. S2CID   205404606.
  44. ↑ Schoenenberger P, Gerosa D, Oertner TG (December 2009). "Temporal control of immediate early gene induction by light". PLOS ONE. 4 (12): e8185. Bibcode:2009PLoSO...4.8185S. doi: 10.1371/journal.pone.0008185 . PMC   2780714 . PMID   19997631.
  45. ↑ Berndt A, Schoenenberger P, Mattis J, Tye KM, Deisseroth K, Hegemann P, et al. (May 2011). "High-efficiency channelrhodopsins for fast neuronal stimulation at low light levels". Proceedings of the National Academy of Sciences of the United States of America. 108 (18): 7595–7600. Bibcode:2011PNAS..108.7595B. doi: 10.1073/pnas.1017210108 . PMC   3088623 . PMID   21504945.
  46. ↑ Dawydow A, Gueta R, Ljaschenko D, Ullrich S, Hermann M, Ehmann N, et al. (September 2014). "Channelrhodopsin-2-XXL, a powerful optogenetic tool for low-light applications". Proceedings of the National Academy of Sciences of the United States of America. 111 (38): 13972–13977. Bibcode:2014PNAS..11113972D. doi: 10.1073/pnas.1408269111 . PMC   4183338 . PMID   25201989.
  47. ↑ Lin JY, Knutsen PM, Muller A, Kleinfeld D, Tsien RY (October 2013). "ReaChR: a red-shifted variant of channelrhodopsin enables deep transcranial optogenetic excitation". Nature Neuroscience. 16 (10): 1499–1508. doi:10.1038/nn.3502. PMC   3793847 . PMID   23995068.
  48. ↑ Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A, Cho YK, et al. (March 2014). "Independent optical excitation of distinct neural populations". Nature Methods. 11 (3): 338–346. doi:10.1038/nmeth.2836. PMC   3943671 . PMID   24509633.
  49. ↑ Hooks BM, Lin JY, Guo C, Svoboda K (March 2015). "Dual-channel circuit mapping reveals sensorimotor convergence in the primary motor cortex". The Journal of Neuroscience. 35 (10): 4418–4426. doi:10.1523/JNEUROSCI.3741-14.2015. PMC   4355205 . PMID   25762684.
  50. ↑ Anisimova M, van Bommel B, Wang R, Mikhaylova M, Wiegert JS, Oertner TG, et al. (December 2022). "Spike-timing-dependent plasticity rewards synchrony rather than causality". Cerebral Cortex. 33 (1): 23–34. doi:10.1093/cercor/bhac050. PMC   9758582 . PMID   35203089.
  51. ↑ Hochbaum DR, Zhao Y, Farhi SL, Klapoetke N, Werley CA, Kapoor V, et al. (August 2014). "All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins". Nature Methods. 11 (8): 825–833. doi:10.1038/nmeth.3000. PMC   4117813 . PMID   24952910.
  52. ↑ Dana H, Mohar B, Sun Y, Narayan S, Gordus A, Hasseman JP, et al. (March 2016). "Sensitive red protein calcium indicators for imaging neural activity". eLife. 5. doi: 10.7554/eLife.12727 . PMC   4846379 . PMID   27011354.
  53. ↑ Afshar Saber W, Gasparoli FM, Dirks MG, Gunn-Moore FJ, Antkowiak M (2018). "All-Optical Assay to Study Biological Neural Networks". Frontiers in Neuroscience. 12: 451. doi: 10.3389/fnins.2018.00451 . PMC   6041400 . PMID   30026684.
  54. ↑ Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG, Bamann C, et al. (April 2011). "Ultra light-sensitive and fast neuronal activation with the Ca²+-permeable channelrhodopsin CatCh". Nature Neuroscience. 14 (4): 513–518. doi:10.1038/nn.2776. PMID   21399632. S2CID   5907240.
  55. ↑ Fernandez Lahore RG, Pampaloni NP, Peter E, Heim MM, Tillert L, Vierock J, et al. (December 2022). "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling". Nature Communications. 13 (1): 7844. Bibcode:2022NatCo..13.7844F. doi:10.1038/s41467-022-35373-4. PMC   9772239 . PMID   36543773.
  56. ↑ Govorunova EG, Gou Y, Sineshchekov OA, Li H, Wang Y, Brown LS, et al. (2021-09-17). "Kalium rhodopsins: Natural light-gated potassium channels". bioRxiv: 2021.09.17.460684. doi:10.1101/2021.09.17.460684. S2CID   237576843.
  57. ↑ Vierock J, Peter E, Grimm C, Rozenberg A, Chen IW, Tillert L, et al. (December 2022). "WiChR, a highly potassium-selective channelrhodopsin for low-light one- and two-photon inhibition of excitable cells". Science Advances. 8 (49): eadd7729. Bibcode:2022SciA....8D7729V. doi:10.1126/sciadv.add7729. PMC   9733931 . PMID   36383037.
  58. 1 2 Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP, et al. (April 2014). "Conversion of channelrhodopsin into a light-gated chloride channel". Science. 344 (6182): 409–412. Bibcode:2014Sci...344..409W. doi: 10.1126/science.1249375 . PMID   24674867. S2CID   206554245.
  59. 1 2 Wietek J, Beltramo R, Scanziani M, Hegemann P, Oertner TG, Wiegert JS (October 2015). "An improved chloride-conducting channelrhodopsin for light-induced inhibition of neuronal activity in vivo". Scientific Reports. 5: 14807. Bibcode:2015NatSR...514807W. doi:10.1038/srep14807. PMC   4595828 . PMID   26443033.
  60. 1 2 Berndt A, Lee SY, Wietek J, Ramakrishnan C, Steinberg EE, Rashid AJ, et al. (January 2016). "Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity". Proceedings of the National Academy of Sciences of the United States of America. 113 (4): 822–829. Bibcode:2016PNAS..113..822B. doi: 10.1073/pnas.1523341113 . PMC   4743797 . PMID   26699459.
  61. ↑ Fernandez Lahore RG, Pampaloni NP, Schiewer E, Heim MM, Tillert L, Vierock J, et al. (2022-12-21). "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling". Nature Communications. 13 (1): 7844. Bibcode:2022NatCo..13.7844F. doi:10.1038/s41467-022-35373-4. ISSN   2041-1723. PMC   9772239 . PMID   36543773.
  62. ↑ Douglass AD, Kraves S, Deisseroth K, Schier AF, Engert F (August 2008). "Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons". Current Biology. 18 (15): 1133–1137. Bibcode:2008CBio...18.1133D. doi:10.1016/j.cub.2008.06.077. PMC   2891506 . PMID   18682213.
  63. ↑ Huber D, Petreanu L, Ghitani N, Ranade S, Hromádka T, Mainen Z, et al. (January 2008). "Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice". Nature. 451 (7174): 61–64. Bibcode:2008Natur.451...61H. doi:10.1038/nature06445. PMC   3425380 . PMID   18094685.
  64. ↑ Han X, Boyden ES (March 2007). "Multiple-color optical activation, silencing, and desynchronization of neural activity, with single-spike temporal resolution". PLOS ONE. 2 (3): e299. Bibcode:2007PLoSO...2..299H. doi: 10.1371/journal.pone.0000299 . PMC   1808431 . PMID   17375185.
  65. ↑ Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, et al. (April 2007). "Multimodal fast optical interrogation of neural circuitry". Nature. 446 (7136): 633–639. Bibcode:2007Natur.446..633Z. doi:10.1038/nature05744. PMID   17410168. S2CID   4415339.
  66. ↑ Govorunova EG, Sineshchekov OA, Janz R, Liu X, Spudich JL (August 2015). "NEUROSCIENCE. Natural light-gated anion channels: A family of microbial rhodopsins for advanced optogenetics". Science. 349 (6248): 647–650. Bibcode:2015Sci...349..647G. doi:10.1126/science.aaa7484. PMC   4764398 . PMID   26113638.
  67. ↑ Klapoetke NC, Murata Y, Kim SS, Pulver SR, Birdsey-Benson A, Cho YK, et al. (March 2014). "Independent optical excitation of distinct neural populations". Nature Methods. 11 (3): 338–346. doi:10.1038/nmeth.2836. PMC   3943671 . PMID   24509633.
  68. ↑ Vierock J, Rodriguez-Rozada S, Dieter A, Pieper F, Sims R, Tenedini F, et al. (July 2021). "BiPOLES is an optogenetic tool developed for bidirectional dual-color control of neurons". Nature Communications. 12 (1): 4527. Bibcode:2021NatCo..12.4527V. doi:10.1038/s41467-021-24759-5. PMC   8313717 . PMID   34312384.
  69. ↑ Zhang YP, Holbro N, Oertner TG (August 2008). "Optical induction of plasticity at single synapses reveals input-specific accumulation of alphaCaMKII". Proceedings of the National Academy of Sciences of the United States of America. 105 (33): 12039–12044. Bibcode:2008PNAS..10512039Z. doi: 10.1073/pnas.0802940105 . PMC   2575337 . PMID   18697934.
  70. ↑ Anisimova M, van Bommel B, Wang R, Mikhaylova M, Simon Wiegert J, Oertner TG, et al. (February 2022). "Spike-timing-dependent plasticity rewards synchrony rather than causality". Cerebral Cortex. 33 (1): 23–34. doi:10.1093/cercor/bhac050. PMC   9758582 . PMID   35203089.
  71. ↑ Xu Z, Ziye X, Craig H, Silvia F (Dec 2013). "Spike-based indirect training of a spiking neural network-controlled virtual insect". 52nd IEEE Conference on Decision and Control. IEEE Decision and Control. pp. 6798–6805. CiteSeerX   10.1.1.671.6351 . doi:10.1109/CDC.2013.6760966. ISBN   978-1-4673-5717-3. S2CID   13992150.
  72. ↑ Petreanu L, Mao T, Sternson SM, Svoboda K (February 2009). "The subcellular organization of neocortical excitatory connections". Nature. 457 (7233): 1142–1145. Bibcode:2009Natur.457.1142P. doi:10.1038/nature07709. PMC   2745650 . PMID   19151697.
  73. ↑ Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, et al. (April 2006). "Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration". Neuron. 50 (1): 23–33. doi:10.1016/j.neuron.2006.02.026. PMC   1459045 . PMID   16600853.
  74. ↑ Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, et al. (April 2006). "Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration". Neuron. 50 (1): 23–33. doi:10.1016/j.neuron.2006.02.026. PMC   1459045 . PMID   16600853.
  75. ↑ Lagali PS, Balya D, Awatramani GB, Münch TA, Kim DS, Busskamp V, et al. (June 2008). "Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration". Nature Neuroscience. 11 (6): 667–675. doi:10.1038/nn.2117. PMID   18432197. S2CID   6798764.
  76. ↑ Sahel JA, Boulanger-Scemama E, Pagot C, Arleo A, Galluppi F, Martel JN, et al. (July 2021). "Partial recovery of visual function in a blind patient after optogenetic therapy". Nature Medicine. 27 (7): 1223–1229. doi: 10.1038/s41591-021-01351-4 . PMID   34031601.
  77. ↑ Gallagher J (24 May 2021). "Algae proteins partially restore man's sight". BBC News.
  78. ↑ Hernandez VH, Gehrt A, Reuter K, Jing Z, Jeschke M, Mendoza Schulz A, et al. (March 2014). "Optogenetic stimulation of the auditory pathway". The Journal of Clinical Investigation. 124 (3): 1114–1129. doi:10.1172/JCI69050. PMC   3934189 . PMID   24509078.
  79. ↑ Mager T, Lopez de la Morena D, Senn V, Schlotte J, D Errico A, Feldbauer K, et al. (May 2018). "High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics". Nature Communications. 9 (1): 1750. Bibcode:2018NatCo...9.1750M. doi:10.1038/s41467-018-04146-3. PMC   5931537 . PMID   29717130.
  80. ↑ Keppeler D, Merino RM, Lopez de la Morena D, Bali B, Huet AT, Gehrt A, et al. (December 2018). "Ultrafast optogenetic stimulation of the auditory pathway by targeting-optimized Chronos". The EMBO Journal. 37 (24): e99649. doi:10.15252/embj.201899649. PMC   6293277 . PMID   30396994.

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