Jump to content

Optogenetics

From Wikipedia, the free encyclopedia
This article is about controlling cellular activity with light. For genetically encoded sensors, see Optogenetic methods to record cellular activity.

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.[1] 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,[2] learning,[3] fear memory,[4] mating,[5] addiction,[6] feeding,[7] and locomotion.[8] In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.[9]

Optogenetic techniques have also been introduced to map the functional connectivity of the brain.[10][11] By altering the activity of genetically labelled neurons with light and by using imaging and electrophysiology techniques to record the activity of other cells, researchers can identify the statistical dependencies between cells and brain regions.[12][13]

In a broader sense, the field of optogenetics also includes methods to record cellular activity with genetically encoded indicators.

In 2010, optogenetics was chosen as the "Method of the Year" across all fields of science and engineering by the interdisciplinary research journal Nature Methods.[14] In the same year an article on "Breakthroughs of the Decade" in the academic research journal Science highlighted optogenetics.[15][16][17]

History

[edit]

In 1979, Francis Crick suggested that controlling all cells of one type in the brain, while leaving the others more or less unaltered, is a real challenge for neuroscience. Crick speculated that a technology using light might be useful to control neuronal activity with temporal and spatial precision but at the time there was no technique to make neurons responsive to light.

By the early 1990s LC Katz and E Callaway had shown that light could uncage glutamate.[18] Heberle and Büldt in 1994 had already shown functional heterologous expression of a bacteriorhodopsin for light-activated ion flow in yeast.[19]

In 1995, Georg Nagel et al. and Ernst Bamberg tried the heterologous expression of microbial rhodopsins (also bacteriorhodopsin and also in a non-neural system, Xenopus oocytes) (Georg Nagel et al., 1995, FEBS Lett.) and showed light-induced current.

The earliest genetically targeted method that used light to control rhodopsin-sensitized neurons was reported in January 2002, by Boris Zemelman and Gero Miesenböck, who employed Drosophila rhodopsin cultured mammalian neurons.[20] In 2003, Zemelman and Miesenböck developed a second method for light-dependent activation of neurons in which single ionotropic channels TRPV1, TRPM8 and P2X2 were gated by photocaged ligands in response to light.[21] Beginning in 2004, the Kramer and Isacoff groups developed organic photoswitches or "reversibly caged" compounds in collaboration with the Trauner group that could interact with genetically introduced ion channels.[22][23] TRPV1 methodology, albeit without the illumination trigger, was subsequently used by several laboratories to alter feeding, locomotion and behavioral resilience in laboratory animals.[24][25][26] However, light-based approaches for altering neuronal activity were not applied outside the original laboratories, likely because the easier to employ channelrhodopsin was cloned soon thereafter.[27]

Peter Hegemann, studying the light response of green algae at the University of Regensburg, had discovered photocurrents that were too fast to be explained by the classic g-protein-coupled animal rhodopsins.[28] Teaming up with the electrophysiologist Georg Nagel at the Max Planck Institute in Frankfurt, they could demonstrate that a single gene from the alga Chlamydomonas produced large photocurrents when expressed in the oocyte of a frog.[29] To identify expressing cells, they replaced the cytoplasmic tail of the algal protein with a fluorescent protein YFP, generating the first generally applicable optogenetic tool.[27] They stated in the 2003 paper that "expression of ChR2 in oocytes or mammalian cells may be used as a powerful tool to increase cytoplasmic Ca2+ concentration or to depolarize the cell membrane, simply by illumination".

Karl Deisseroth in the Bioengineering Department at Stanford published the notebook pages from early July 2004 of his initial experiment showing light activation of neurons expressing a channelrhodopsin.[30] In August 2005, his laboratory staff, including graduate students Ed Boyden and Feng Zhang, in collaboration with Georg Nagel, published the first demonstration of a single-component optogenetic system, in neurons[31] using the channelrhodopsin-2(H134R)-eYFP mutant from Georg Nagel, which is the first mutant of channelrhodopsin-2 since its functional characterization by Georg Nagel and Hegemann.[27]

Zhuo-Hua Pan of Wayne State University, researching on restore sight to blindness, tried channelrhodopsin out in ganglion cells—the neurons in human eyes that connect directly to the brain. Pan's first observation of optical activation of retinal neurons with channelrhodopsin was in February 2004 according to Pan,[32] five months before Deisseroth's initial observation in July 2004.[33] Indeed, the transfected neurons became electrically active in response to light, and in 2005 Zhuo-Hua Pan reported successful in-vivo transfection of channelrhodopsin in retinal ganglion cells of mice, and electrical responses to photostimulation in retinal slice culture.[34] This approach was eventually realized in a human patient by Botond Roska and coworkers in 2021.[9]

In April 2005, Susana Lima and Miesenböck reported the first use of genetically targeted P2X2 photostimulation to control the behaviour of an animal.[35] They showed that photostimulation of genetically circumscribed groups of neurons, such as those of the dopaminergic system, elicited characteristic behavioural changes in fruit flies.

In October 2005, Lynn Landmesser and Stefan Herlitze also published the use of channelrohodpsin-2 to control neuronal activity in cultured hippocampal neurons and chicken spinal cord circuits in intact developing embryos.[36] In addition, they introduced for the first time vertebrate rhodopsin, a light-activated G protein coupled receptor, as a tool to inhibit neuronal activity via the recruitment of intracellular signaling pathways also in hippocampal neurons and the intact developing chicken embryo.[36]

The groups of Alexander Gottschalk and Georg Nagel made the first ChR2 mutant (H134R) and were first to use channelrhodopsin-2 for controlling neuronal activity in an intact animal, showing that motor patterns in the roundworm C. elegans could be evoked by light stimulation of genetically selected neural circuits (published in December 2005).[37] In mice, controlled expression of optogenetic tools is often achieved with cell-type-specific Cre/loxP methods developed for neuroscience by Joe Z. Tsien back in the 1990s[38] to activate or inhibit specific brain regions and cell-types in vivo.[39]

In 2007, the labs of Boyden and Deisseroth (together with the groups of Gottschalk and Georg Nagel) simultaneously reported successful optogenetic inhibition of activity in neurons.[40][41]

In 2007, Georg Nagel and Hegemann's groups started the optogenetic manipulation of cAMP.[42] In 2014, Avelar et al. reported the first rhodopsin-guanylyl cyclase gene from fungus. In 2015, Scheib et al. and Gao et al. characterized the activity of the rhodopsin-guanylyl cyclase gene. And Shiqiang Gao et al. and Georg Nagel, Alexander Gottschalk identified it as the first 8 TM rhodopsin.[43]

Description

[edit]
Fig 1. Channelrhodopsin-2 (ChR2) induces temporally precise blue light-driven activity in rat prelimbic prefrontal cortical neurons. a) In vitro schematic (left) showing blue light delivery and whole-cell patch-clamp recording of light-evoked activity from a fluorescent CaMKllα::ChR2-EYFP expressing pyramidal neuron (right) in an acute brain slice. b) In vivo schematic (left) showing blue light (473 nm) delivery and single-unit recording. (bottom left) Coronal brain slice showing expression of CaMKllα::ChR2-EYFP in the prelimbic region. Light blue arrow shows tip of the optical fiber; black arrow shows tip of the recording electrode (left). White bar, 100 μm. (bottom right) In vivo light recording of prefrontal cortical neuron in a transduced CaMKllα::ChR2-EYFP rat showing light-evoked spiking to 20 Hz delivery of blue light pulses (right). Inset, representative light-evoked single-unit response.[44]
Fig 2. Halorhodopsin (NpHR) rapidly and reversibly silences spontaneous activity in vivo in rat prelimbic prefrontal cortex. (Top left) Schematic showing in vivo green (532 nm) light delivery and single- unit recording of a spontaneously active CaMKllα::eNpHR3.0- EYFP expressing pyramidal neuron. (Right) Example trace showing that continuous 532 nm illumination inhibits single-unit activity in vivo. Inset, representative single unit event; Green bar, 10 seconds.[44]
A nematode expressing the light-sensitive ion channel Mac. Mac is a proton pump originally isolated in the fungus Leptosphaeria maculans and now expressed in the muscle cells of C. elegans that opens in response to green light and causes hyperpolarizing inhibition. Of note is the extension in body length that the worm undergoes each time it is exposed to green light, which is presumably caused by Mac's muscle-relaxant effects.[45]
A nematode expressing ChR2 in its gubernacular-oblique muscle group responding to stimulation by blue light. Blue light stimulation causes the gubernacular-oblique muscles to repeatedly contract, causing repetitive thrusts of the spicule, as would be seen naturally during copulation.[46]

Optogenetics provides millisecond-scale temporal precision which allows the experimenter to keep pace with fast biological information processing (for example, in probing the causal role of specific action potential patterns in defined neurons). Indeed, to probe the neural code, optogenetics by definition must operate on the millisecond timescale to allow addition or deletion of precise activity patterns within specific cells in the brains of intact animals, including mammals (see Figure 1). By comparison, the temporal precision of traditional genetic manipulations (employed to probe the causal role of specific genes within cells, via "loss-of-function" or "gain of function" changes in these genes) is rather slow, from hours or days to months. It is important to also have fast readouts in optogenetics that can keep pace with the optical control. This can be done with electrical recordings ("optrodes") or with reporter proteins that are biosensors, where scientists have fused fluorescent proteins to detector proteins. Additionally, beyond its scientific impact optogenetics represents an important case study in the value of both ecological conservation (as many of the key tools of optogenetics arise from microbial organisms occupying specialized environmental niches), and in the importance of pure basic science as these opsins were studied over decades for their own sake by biophysicists and microbiologists, without involving consideration of their potential value in delivering insights into neuroscience and neuropsychiatric disease.[47]

Light-activated proteins: channels, pumps and enzymes

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 channelrhodopsins (ChR2, ChR1, VChR1, and SFOs) to excite neurons and anion-conducting channelrhodopsins for light-induced inhibition. Indirectly light-controlled potassium channels have recently been engineered to prevent action potential generation in neurons during blue light illumination.[48][49] Light-driven ion pumps are also used to inhibit neuronal activity, e.g. halorhodopsin (NpHR),[50] enhanced halorhodopsins (eNpHR2.0 and eNpHR3.0, see Figure 2),[51] archaerhodopsin (Arch), fungal opsins (Mac) and enhanced bacteriorhodopsin (eBR).[52]

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[53] a family of 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.[54] 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.[55][56][57] Photoactivated adenylyl cyclases have been discovered in fungi and successfully used to control cAMP levels in mammalian neurons.[58][59] This emerging repertoire of optogenetic actuators now allows cell-type-specific and temporally precise control of multiple axes of cellular function within intact animals.[60]

Hardware for light application

Another necessary factor is hardware (e.g. integrated fiberoptic and solid-state light sources) to allow specific cell types, even deep within the brain, to be controlled in freely behaving animals. Most commonly, the latter is now achieved using the fiberoptic-coupled diode technology introduced in 2007,[61][62][63] though to avoid use of implanted electrodes, researchers have engineered ways to inscribe a "window" made of zirconia that has been modified to be transparent and implanted in mice skulls, to allow optical waves to penetrate more deeply to stimulate or inhibit individual neurons.[64] To stimulate superficial brain areas such as the cerebral cortex, optical fibers or LEDs can be directly mounted to the skull of the animal. More deeply implanted optical fibers have been used to deliver light to deeper brain areas.[65] Complementary to fiber-tethered approaches, completely wireless techniques have been developed utilizing wirelessly delivered power to headborne LEDs for unhindered study of complex behaviors in freely behaving organisms.[66]

Expression of optogenetic actuators

Optogenetics also necessarily includes the development of genetic targeting strategies such as cell-specific promoters or other customized conditionally-active viruses, to deliver the light-sensitive probes to specific populations of neurons in the brain of living animals (e.g. worms, fruit flies, mice, rats, and monkeys). In invertebrates such as worms and fruit flies some amount of all-trans-retinal (ATR) is supplemented with food. A key advantage of microbial opsins as noted above is that they are fully functional without the addition of exogenous co-factors in vertebrates.[63]

Technique

[edit]
Three primary components in the application of optogenetics are as follows (A) Identification or synthesis of a light-sensitive protein (opsin) such as channelrhodopsin-2 (ChR2), halorhodopsin (NpHR), etc... (B) The design of a system to introduce the genetic material containing the opsin into cells for protein expression such as application of Cre recombinase or an adeno-associated-virus (C) application of light emitting instruments.[67]

The technique of using optogenetics is flexible and adaptable to the experimenter's needs. Cation-selective channelrhodopsins (e.g. ChR2) are used to excite neurons, anion-conducting channelrhodopsins (e.g. GtACR2) inhibit neuronal activity. Combining these tools into a single construct (e.g. BiPOLES) allows for both inhibition and excitation, depending on the wavelength of illumination.[68]

Introducing the microbial opsin into a specific subset of cells is challenging. A popular approach is to introduce an engineered viral vector that contains the optogenetic actuator gene attached to a specific promoter such as CAMKIIα, which is active in excitatory neurons. This allows for some level of specificity, preventing e.g. expression in glia cells.[69]

A more specific approach is based on transgenic "driver" mice which express Cre recombinase, an enzyme that catalyzes recombination between two lox-P sites, in a specific subset of cells, e.g. parvalbumin-expressing interneurons. By introducing an engineered viral vector containing the optogenetic actuator gene in between two lox-P sites, only the cells producing Cre recombinase will express the microbial opsin. This technique has allowed for multiple modified optogenetic actuators to be used without the need to create a whole line of transgenic animals every time a new microbial opsin is needed.[70]

After the introduction and expression of the microbial opsin, a computer-controlled light source has to be optically coupled to the brain region in question. Light-emitting diodes (LEDs) or fiber-coupled diode-pumped solid-state lasers (DPSS) are frequently used. Recent advances include the advent of wireless head-mounted devices that apply LEDs to the targeted areas and as a result, give the animals more freedom to move.[71][72]

Fiber-based approaches can also be used to combine optical stimulation and calcium imaging.[65] This enables researchers to visualize and manipulate the activity of single neurons in awake behaving animals.[73] It is also possible to record from multiple deep brain regions at the same using GRIN lenses connected via optical fiber to an externally positioned photodetector and photostimulator.[74][75]

Technical challenges

[edit]

Selective expression

[edit]

One of the main problems of optogenetics is that not all the cells in question may express the microbial opsin gene at the same level. Thus, even illumination with a defined light intensity will have variable effects on individual cells. Optogenetic stimulation of neurons in the brain is even less controlled as the light intensity drops exponentially from the light source (e.g. implanted optical fiber).

It remains difficult to target opsin to defined subcellular compartments, e.g. the plasma membrane, synaptic vesicles, or mitochondria.[51][76] Restricting the opsin to specific regions of the plasma membrane such as dendrites, somata or axon terminals provides a more robust understanding of neuronal circuitry.[76]

Mathematical modelling shows that selective expression of opsin in specific cell types can dramatically alter the dynamical behavior of the neural circuitry. In particular, optogenetic stimulation that preferentially targets inhibitory cells can transform the excitability of the neural tissue, affecting non-transfected neurons as well.[77]

Kinetics and synchronization

[edit]

The original channelrhodopsin-2 was slower closing than typical cation channels of cortical neurons, leading to prolonged depolarization and calcium influx.[78] Many channelrhodopsin variants with more favorable kinetics have since been engineered.[55] [56]

A difference between natural spike patterns and optogenetic activation is that pulsed light stimulation produces synchronous activation of expressing neurons, which removes the possibility of sequential activity in the stimulated population. Therefore, it is difficult to understand how the cells in the population affected communicate with one another or how their phasic properties of activation relate to circuit function.

Optogenetic activation has been combined with functional magnetic resonance imaging (ofMRI) to elucidate the connectome, a thorough map of the brain's neural connections.[76][79] Precisely timed optogenetic activation is used to calibrate the delayed hemodynamic signal (BOLD) fMRI is based on.

Light absorption spectrum

[edit]

The opsin proteins currently in use have absorption peaks across the visual spectrum, but remain considerably sensitive to blue light.[76] This spectral overlap makes it very difficult to combine opsin activation with genetically encoded indicators (GEVIs, GECIs, GluSnFR, synapto-pHluorin), most of which need blue light excitation. Opsins with infrared activation would, at a standard irradiance value, increase light penetration and augment resolution through reduction of light scattering.

Spatial response

[edit]

Due to scattering, a narrow light beam to stimulate neurons in a patch of neural tissue can evoke a response profile that is much broader than the stimulation beam.[80] In this case, neurons may be activated (or inhibited) unintentionally. Computational simulation tools[81][82] are used to estimate the volume of stimulated tissue for different wavelengths of light.

Applications

[edit]

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[1],[83] Parkinson's disease[84][85] and other neurological and psychiatric disorders such as autism, Schizophrenia, drug abuse, anxiety, and depression.[52][86][87][88] An experimental treatment for blindness involves a channel rhodopsin expressed in ganglion cells, stimulated with light patterns from engineered goggles.[89][9]

Identification of particular neurons and networks

[edit]

Amygdala

[edit]

Optogenetic approaches have been used to map neural circuits in the amygdala that contribute to fear conditioning.[90][91][92][93] One such example of a neural circuit is the connection made from the basolateral amygdala to the dorsal-medial prefrontal cortex where neuronal oscillations of 4 Hz have been observed in correlation to fear induced freezing behaviors in mice. Transgenic mice were introduced with channelrhodoposin-2 attached with a parvalbumin-Cre promoter that selectively infected interneurons located both in the basolateral amygdala and the dorsal-medial prefrontal cortex responsible for the 4 Hz oscillations. The interneurons were optically stimulated generating a freezing behavior and as a result provided evidence that these 4 Hz oscillations may be responsible for the basic fear response produced by the neuronal populations along the dorsal-medial prefrontal cortex and basolateral amygdala.[94]

Olfactory bulb

[edit]

Optogenetic activation of olfactory sensory neurons was critical for demonstrating timing in odor processing[95] and for mechanism of neuromodulatory mediated olfactory guided behaviors (e.g. aggression, mating)[96] In addition, with the aid of optogenetics, evidence has been reproduced to show that the "afterimage" of odors is concentrated more centrally around the olfactory bulb rather than on the periphery where the olfactory receptor neurons would be located. Transgenic mice infected with channel-rhodopsin Thy1-ChR2, were stimulated with a 473 nm laser transcranially positioned over the dorsal section of the olfactory bulb. Longer photostimulation of mitral cells in the olfactory bulb led to observations of longer lasting neuronal activity in the region after the photostimulation had ceased, meaning the olfactory sensory system is able to undergo long term changes and recognize differences between old and new odors.[97]

Nucleus accumbens

[edit]

Optogenetics, freely moving mammalian behavior, in vivo electrophysiology, and slice physiology have been integrated to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of the total population of accumbal neurons, these cholinergic cells are able to control the activity of the dopaminergic terminals that innervate medium spiny neurons (MSNs) in the nucleus accumbens.[98] These accumbal MSNs are known to be involved in the neural pathway through which cocaine exerts its effects, because decreasing cocaine-induced changes in the activity of these neurons has been shown to inhibit cocaine conditioning. The few cholinergic neurons present in the nucleus accumbens may prove viable targets for pharmacotherapy in the treatment of cocaine dependence[52]

Prefrontal cortex

[edit]
Cages for rat equipped with optogenetic LED commutators which permit in vivo study of animal behavior during optogenetic stimulations

In vivo and in vitro recordings from the University of Colorado, Boulder Optophysiology Laboratory of Donald C. Cooper Ph.D. showing individual CAMKII AAV-ChR2 expressing pyramidal neurons within the prefrontal cortex that demonstrated high fidelity action potential output with short pulses of blue light at 20 Hz (Figure 1).[44]

Motor cortex

In vivo repeated optogenetic stimulation in healthy animals was able to eventually induce seizures.[99] This model has been termed optokindling.

Piriform cortex

In vivo repeated optogenetic stimulation of pyramidal cells of the piriform cortex in healthy animals was able to eventually induce seizures.[100] In vitro studies have revealed a loss of feedback inhibition in the piriform circuit due to impaired GABA synthesis.[100]

Heart

[edit]

Optogenetics was applied on atrial cardiomyocytes to end spiral wave arrhythmias, found to occur in atrial fibrillation, with light.[101] This method is still in the development stage. A recent study explored the possibilities of optogenetics as a method to correct for arrhythmias and resynchronize cardiac pacing. The study introduced channelrhodopsin-2 into cardiomyocytes in ventricular areas of hearts of transgenic mice and performed in vitro studies of photostimulation on both open-cavity and closed-cavity mice. Photostimulation led to increased activation of cells and thus increased ventricular contractions resulting in increasing heart rates. In addition, this approach has been applied in cardiac resynchronization therapy (CRT) as a new biological pacemaker as a substitute for electrode based-CRT.[102] Lately, optogenetics has been used in the heart to defibrillate ventricular arrhythmias with local epicardial illumination,[103] a generalized whole heart illumination[104] or with customized stimulation patterns based on arrhythmogenic mechanisms in order to lower defibrillation energy.[105]

Spiral ganglion

[edit]

Optogenetic stimulation of the spiral ganglion in deaf mice restored auditory activity.[106] Optogenetic application onto the cochlear region allows for the stimulation or inhibition of the spiral ganglion cells (SGN). In addition, due to the characteristics of the resting potentials of SGN's, different variants of the protein channelrhodopsin-2 have been employed such as Chronos,[107] CatCh and f-Chrimson.[108] Chronos and CatCh variants are particularly useful in that they have less time spent in their deactivated states, which allow for more activity with less bursts of blue light emitted. Additionally, using engineered red-shifted channels as f-Chrimson allow for stimulation using longer wavelengths, which decreases the potential risks of phototoxicity in the long term without compromising gating speed.[109] The result being that the LED producing the light would require less energy and the idea of cochlear prosthetics in association with photo-stimulation, would be more feasible.[110]

Brainstem

[edit]

Optogenetic stimulation of a modified red-light excitable channelrhodopsin (ReaChR) expressed in the facial motor nucleus enabled minimally invasive activation of motoneurons effective in driving whisker movements in mice.[111] One novel study employed optogenetics on the Dorsal Raphe Nucleus to both activate and inhibit dopaminergic release onto the ventral tegmental area. To produce activation transgenic mice were infected with channelrhodopsin-2 with a TH-Cre promoter and to produce inhibition the hyperpolarizing opsin NpHR was added onto the TH-Cre promoter. Results showed that optically activating dopaminergic neurons led to an increase in social interactions, and their inhibition decreased the need to socialize only after a period of isolation.[112]

Visual system

[edit]

Studying the visual system using optogenetics can be challenging. Indeed, the light used for optogenetic control may lead to the activation of photoreceptors, as a result of the proximity between primary visual circuits and these photoreceptors. In this case, spatial selectivity is difficult to achieve (particularly in the case of the fly optic lobe). Thus, the study of the visual system requires spectral separation, using channels that are activated by different wavelengths of light than rhodopsins within the photoreceptors (peak activation at 480 nm for Rhodopsin 1 in Drosophila). Red-shifted CsChrimson[113] or bistable Channelrhodopsin[114] are used for optogenetic activation of neurons (i.e. depolarization), as both allow spectral separation. In order to achieve neuronal silencing (i.e. hyperpolarization), an anion channelrhodopsin discovered in the cryptophyte algae species Guillardia theta (named GtACR1).[115] can be used. GtACR1 is more light sensitive than other inhibitory channels such as the Halorhodopsin class of chlorid pumps and imparts a strong conductance. As its activation peak (515 nm) is close to that of Rhodopsin 1, it is necessary to carefully calibrate the optogenetic illumination as well as the visual stimulus. The factors to take into account are the wavelength of the optogenetic illumination (possibly higher than the activation peak of GtACR1), the size of the stimulus (in order to avoid the activation of the channels by the stimulus light) and the intensity of the optogenetic illumination. It has been shown that GtACR1 can be a useful inhibitory tool in optogenetic study of Drosophila's visual system by silencing T4/T5 neurons expression.[116] These studies can also be led on intact behaving animals, for instance to probe optomotor response.

Sensorimotor system

[edit]

Optogenetically inhibiting or activating neurons tests their necessity and sufficiency, respectively, in generating a behavior.[117] Using this approach, researchers can dissect the neural circuitry controlling motor output. By perturbing neurons at various places in the sensorimotor system, researchers have learned about the role of descending neurons in eliciting stereotyped behaviors,[118] how localized tactile sensory input[119] and activity of interneurons[120] alters locomotion, and the role of Purkinje cells in generating and modulating movement.[121] This is a powerful technique for understanding the neural underpinnings of animal locomotion and movement more broadly.

Precise temporal control of interventions

[edit]

The currently available optogenetic actuators allow for the accurate temporal control of the required intervention (i.e. inhibition or excitation of the target neurons) with precision routinely going down to the millisecond level.[122] The temporal precision varies, however, across optogenetic actuators,[123] and depends on the frequency and intensity of the stimulation.[80]

Experiments can now be devised where the light used for the intervention is triggered by a particular element of behavior (to inhibit the behavior), a particular unconditioned stimulus (to associate something to that stimulus) or a particular oscillatory event in the brain (to inhibit the event).[124][125] This kind of approach has already been used in several brain regions:

Hippocampus

[edit]

Sharp waves and ripple complexes (SWRs) are distinct high frequency oscillatory events in the hippocampus thought to play a role in memory formation and consolidation. These events can be readily detected by following the oscillatory cycles of the on-line recorded local field potential. In this way the onset of the event can be used as a trigger signal for a light flash that is guided back into the hippocampus to inhibit neurons specifically during the SWRs and also to optogenetically inhibit the oscillation itself.[126] These kinds of "closed-loop" experiments are useful to study SWR complexes and their role in memory.

Cellular biology/cell signaling pathways

[edit]
Optogenetic control of cellular forces and induction of mechanotransduction.[127] Pictured cells receive an hour of imaging concurrent with blue light that pulses every 60 seconds. This is also indicated when the blue point flashes onto the image. The cell relaxes for an hour without light activation and then this cycle repeats again. The square inset magnifies the cell's nucleus.

Analogously to how natural light-gated ion channels such as channelrhodopsin-2 allows optical control of ion flux, which is especially useful in neuroscience, natural light-controlled signal transduction proteins also allow optical control of biochemical pathways, including both second-messenger generation and protein-protein interactions, which is especially useful in studying cell and developmental biology.[128] In 2002, the first example of using photoproteins from another organism for controlling a biochemical pathway was demonstrated using the light-induced interaction between plant phytochrome and phytochrome-interacting factor (PIF) to control gene transcription in yeast.[1] By fusing phytochrome to a DNA-binding domain and PIF to a transcriptional activation domain, transcriptional activation of genes recognized by the DNA-binding domain could be induced by light.[1] This study anticipated aspects of the later development of optogenetics in the brain, for example, by suggesting that "Directed light delivery by fiber optics has the potential to target selected cells or tissues, even within larger, more-opaque organisms."[1] The literature has been inconsistent as to whether control of cellular biochemistry with photoproteins should be subsumed within the definition of optogenetics, as optogenetics in common usage refers specifically to the control of neuronal firing with opsins,[129][130][17][131] and as control of neuronal firing with opsins postdates and uses distinct mechanisms from control of cellular biochemistry with photoproteins.[128]

Photosensitive proteins used in various cell signaling pathways

[edit]

In addition to phytochromes, which are found in plants and cyanobacteria, LOV domains(Light-oxygen-voltage-sensing domain) from plants and yeast and cryptochrome domains from plants are other natural photosensory domains that have been used for optical control of biochemical pathways in cells.[132][128] In addition, a synthetic photosensory domain has been engineered from the fluorescent protein Dronpa for optical control of biochemical pathways.[128] In photosensory domains, light absorption is either coupled to a change in protein-protein interactions (in the case of phytochromes, some LOV domains, cryptochromes, and Dronpa mutants) or a conformational change that exposes a linked protein segment or alters the activity of a linked protein domain (in the case of phytochromes and some LOV domains).[128] Light-regulated protein-protein interactions can then be used to recruit proteins to DNA, for example to induce gene transcription or DNA modifications, or to the plasma membrane, for example to activate resident signaling proteins.[127][133][134][135][136][137] CRY2 also clusters when active, so has been fused with signaling domains and subsequently photoactivated to allow for clustering-based activation.[138] The LOV2 domain of Avena sativa(common oat) has been used to expose short peptides or an active protein domain in a light-dependent manner.[139][140][141] Introduction of this LOV domain into another protein can regulate function through light induced peptide disorder.[142] The asLOV2 protein, which optogenetically exposes a peptide, has also been used as a scaffold for several synthetic light induced dimerization and light induced dissociation systems (iLID and LOVTRAP, respectively).[143][144] The systems can be used to control proteins through a protein splitting strategy.[145] Photodissociable Dronpa domains have also been used to cage a protein active site in the dark, uncage it after cyan light illumination, and recage it after violet light illumination.[146]

Temporal control of signal transduction with light

[edit]

The ability to optically control signals for various time durations is being explored to elucidate how cell signaling pathways convert signal duration and response to different outputs.[147] Natural signaling cascades are capable of responding with different outputs to differences in stimulus timing duration and dynamics.[148] For example, treating PC12 cells with epidermal growth factor (EGF, inducing a transient profile of ERK activity) leads to cellular proliferation whereas introduction of nerve growth factor (NGF, inducing a sustained profile of ERK activity) leads to differentiation into neuron-like cells.[149] This behavior was initially characterized using EGF and NGF application, but the finding has been partially replicated with optical inputs.[150] In addition, a rapid negative feedback loop in the RAF-MEK-ERK pathway was discovered using pulsatile activation of a photoswitchable RAF engineered with photodissociable Dronpa domains.[146]

Optogenetic noise-photostimulation

[edit]

Professor Elias Manjarrez's research group introduced the Optogenetic noise-photostimulation.[151][152][153] This is a technique that uses random noisy light to activate neurons expressing ChR2. An optimal level of optogenetic-noise photostimulation on the brain can increase the somatosensory evoked field potentials, the firing frequency response of pyramidal neurons to somatosensory stimulation, and the sodium current amplitude.

Awards

[edit]

The powerful impact of optogenetic technology on brain research has been recognized by numerous awards to key players in the field.

In 2010, Georg Nagel, Peter Hegemann and Ernst Bamberg were awarded the Wiley Prize in Biomedical Sciences[154] and they were also among those awarded the Karl Heinz Beckurts Prize in 2010.[155] In the same year, Karl Deisseroth was awarded the inaugural HFSP Nakasone Award for "his pioneering work on the development of optogenetic methods for studying the function of neuronal networks underlying behavior".[156]

In 2012, Bamberg, Deisseroth, Hegemann and Georg Nagel were awarded the Zülch Prize by the Max Planck Society,[157] and Miesenböck was awarded the Baillet Latour Health Prize for "having pioneered optogenetic approaches to manipulate neuronal activity and to control animal behaviour."[158]

In 2013, Georg Nagel and Hegemann were among those awarded the Louis-Jeantet Prize for Medicine.[159] Also that year, year Bamberg, Boyden, Deisseroth, Hegemann, Miesenböck and Georg Nagel were jointly awarded The Brain Prize for "their invention and refinement of optogenetics."[160][161]

In 2017, Deisseroth was awarded the Else Kröner Fresenius Research Prize for "his discoveries in optogenetics and hydrogel-tissue chemistry, as well as his research into the neural circuit basis of depression."[162]

In 2018, the Inamori Foundation presented Deisseroth with the Kyoto Prize for "spearheading optogenetics" and "revolutionizing systems neuroscience research."[163]

In 2019, Bamberg, Boyden, Deisseroth, Hegemann, Miesenböck and Georg Nagel were awarded the Rumford Prize by the American Academy of Arts and Sciences in recognition of "their extraordinary contributions related to the invention and refinement of optogenetics."[164]

In 2020, Deisseroth was awarded the Heineken Prize for Medicine from the Royal Netherlands Academy of Arts and Sciences, for developing optogenetics and hydrogel-tissue chemistry.[165]

In 2020, Miesenböck, Hegemann and Georg Nagel jointly received the Shaw Prize in Life Science and Medicine.[166]

In 2021, Hegemann, Deisseroth and Dieter Oesterhelt received the Albert Lasker Award for Basic Medical Research.

References

[edit]
  1. ^ a b c d Shimizu-Sato S, Huq E, Tepperman JM, Quail PH (October 2002). "A light-switchable gene promoter system". Nature Biotechnology. 20 (10): 1041–1044. doi:10.1038/nbt734. PMID 12219076. S2CID 24914960.
  2. ^ Guo ZV, Li N, Huber D, Ophir E, Gutnisky D, Ting JT, et al. (January 2014). "Flow of cortical activity underlying a tactile decision in mice". Neuron. 81 (1): 179–194. doi:10.1016/j.neuron.2013.10.020. PMC 3984938. PMID 24361077.
  3. ^ Lak A, Okun M, Moss MM, Gurnani H, Farrell K, Wells MJ, et al. (February 2020). "Dopaminergic and Prefrontal Basis of Learning from Sensory Confidence and Reward Value". Neuron. 105 (4): 700–711.e6. doi:10.1016/j.neuron.2019.11.018. PMC 7031700. PMID 31859030.
  4. ^ Liu X, Ramirez S, Pang PT, Puryear CB, Govindarajan A, Deisseroth K, Tonegawa S (March 2012). "Optogenetic stimulation of a hippocampal engram activates fear memory recall". Nature. 484 (7394): 381–385. Bibcode:2012Natur.484..381L. doi:10.1038/nature11028. PMC 3331914. PMID 22441246.
  5. ^ Tanaka R, Higuchi T, Kohatsu S, Sato K, Yamamoto D (November 2017). "Optogenetic Activation of the fruitless-Labeled Circuitry in Drosophila subobscura Males Induces Mating Motor Acts". The Journal of Neuroscience. 37 (48): 11662–11674. doi:10.1523/JNEUROSCI.1943-17.2017. PMC 6705751. PMID 29109241.
  6. ^ Stamatakis AM, Stuber GD (November 2012). "Optogenetic strategies to dissect the neural circuits that underlie reward and addiction". Cold Spring Harbor Perspectives in Medicine. 2 (11): a011924. doi:10.1101/cshperspect.a011924. PMC 3543095. PMID 23043156.
  7. ^ Musso, Pierre-Yves; Junca, Pierre; Jelen, Meghan; Feldman-Kiss, Damian; Zhang, Han; Chan, Rachel CW; Gordon, Michael D (2019-07-19). Ramaswami, Mani; Dulac, Catherine (eds.). "Closed-loop optogenetic activation of peripheral or central neurons modulates feeding in freely moving Drosophila". eLife. 8: e45636. doi:10.7554/eLife.45636. ISSN 2050-084X. PMC 6668987. PMID 31322499.
  8. ^ Feng, Kai; Sen, Rajyashree; Minegishi, Ryo; Dübbert, Michael; Bockemühl, Till; Büschges, Ansgar; Dickson, Barry J. (2020-12-02). "Distributed control of motor circuits for backward walking in Drosophila". Nature Communications. 11 (1): 6166. Bibcode:2020NatCo..11.6166F. doi:10.1038/s41467-020-19936-x. ISSN 2041-1723. PMC 7710706. PMID 33268800. S2CID 227255627.
  9. ^ a b c 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.
  10. ^ Lim, Diana; LeDue, Jeffrey; Mohajerani, Majid; Vanni, Matthieu; Murphy, Timothy (2013). "Optogenetic approaches for functional mouse brain mapping". Frontiers in Neuroscience. 7: 54. doi:10.3389/fnins.2013.00054. ISSN 1662-453X. PMC 3622058. PMID 23596383.
  11. ^ Lee, Candice; Lavoie, Andreanne; Liu, Jiashu; Chen, Simon X.; Liu, Bao-hua (2020). "Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits". Frontiers in Neural Circuits. 14: 18. doi:10.3389/fncir.2020.00018. ISSN 1662-5110. PMC 7193678. PMID 32390806.
  12. ^ Franconville, Romain; Beron, Celia; Jayaraman, Vivek (2018-08-20). VijayRaghavan, K; Scott, Kristin; Heinze, Stanley (eds.). "Building a functional connectome of the Drosophila central complex". eLife. 7: e37017. doi:10.7554/eLife.37017. ISSN 2050-084X. PMC 6150698. PMID 30124430.
  13. ^ Chen, Chenghao; Agrawal, Sweta; Mark, Brandon; Mamiya, Akira; Sustar, Anne; Phelps, Jasper S.; Lee, Wei-Chung Allen; Dickson, Barry J.; Card, Gwyneth M.; Tuthill, John C. (2021-12-06). "Functional architecture of neural circuits for leg proprioception in Drosophila". Current Biology. 31 (23): 5163–5175.e7. Bibcode:2021CBio...31E5163C. doi:10.1016/j.cub.2021.09.035. ISSN 0960-9822. PMC 8665017. PMID 34637749.
  14. ^ Primer on Optogenetics: Pastrana E (2010). "Optogenetics: Controlling cell function with light". Nature Methods. 8 (1): 24–25. doi:10.1038/nmeth.f.323. S2CID 5808517.
    Editorial: "Method of the Year 2010". Nature Methods. 8 (1): 1. 2010. doi:10.1038/nmeth.f.321.
    Commentary: Deisseroth K (January 2011). "Optogenetics". Nature Methods. 8 (1): 26–29. doi:10.1038/nmeth.f.324. PMC 6814250. PMID 21191368.
  15. ^ News Staff (December 2010). "Insights of the decade. Stepping away from the trees for a look at the forest. Introduction". Science. 330 (6011): 1612–1613. Bibcode:2010Sci...330.1612.. doi:10.1126/science.330.6011.1612. PMID 21163985. S2CID 206593135.
  16. ^ "Method of the Year 2010: Optogenetics". Nature Video. 17 December 2010.
  17. ^ a b Deisseroth K (20 October 2010). "Optogenetics: Controlling the Brain with Light". Scientific American. Springer Nature America, Inc.
  18. ^ Crick F (December 1999). "The impact of molecular biology on neuroscience". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 354 (1392): 2021–2025. doi:10.1098/rstb.1999.0541. PMC 1692710. PMID 10670022.
  19. ^ Hoffmann A, Hildebrandt V, Heberle J, Büldt G (September 1994). "Photoactive mitochondria: in vivo transfer of a light-driven proton pump into the inner mitochondrial membrane of Schizosaccharomyces pombe". Proceedings of the National Academy of Sciences of the United States of America. 91 (20): 9367–9371. Bibcode:1994PNAS...91.9367H. doi:10.1073/pnas.91.20.9367. PMC 44813. PMID 7937771.
  20. ^ Zemelman BV, Lee GA, Ng M, Miesenböck G (January 2002). "Selective photostimulation of genetically chARGed neurons". Neuron. 33 (1): 15–22. doi:10.1016/S0896-6273(01)00574-8. PMID 11779476. S2CID 16391269.
  21. ^ Zemelman BV, Nesnas N, Lee GA, Miesenbock G (February 2003). "Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons". Proceedings of the National Academy of Sciences of the United States of America. 100 (3): 1352–1357. Bibcode:2003PNAS..100.1352Z. doi:10.1073/pnas.242738899. PMC 298776. PMID 12540832.
  22. ^ Banghart M, Borges K, Isacoff E, Trauner D, Kramer RH (December 2004). "Light-activated ion channels for remote control of neuronal firing". Nature Neuroscience. 7 (12): 1381–1386. doi:10.1038/nn1356. PMC 1447674. PMID 15558062.
  23. ^ Volgraf M, Gorostiza P, Numano R, Kramer RH, Isacoff EY, Trauner D (January 2006). "Allosteric control of an ionotropic glutamate receptor with an optical switch". Nature Chemical Biology. 2 (1): 47–52. doi:10.1038/nchembio756. PMC 1447676. PMID 16408092.
  24. ^ Arenkiel BR, Klein ME, Davison IG, Katz LC, Ehlers MD (April 2008). "Genetic control of neuronal activity in mice conditionally expressing TRPV1". Nature Methods. 5 (4): 299–302. doi:10.1038/nmeth.1190. PMC 3127246. PMID 18327266.
  25. ^ Güler AD, Rainwater A, Parker JG, Jones GL, Argilli E, Arenkiel BR, et al. (March 2012). "Transient activation of specific neurons in mice by selective expression of the capsaicin receptor". Nature Communications. 3: 746. Bibcode:2012NatCo...3..746G. doi:10.1038/ncomms1749. PMC 3592340. PMID 22434189.
  26. ^ Wang M, Perova Z, Arenkiel BR, Li B (May 2014). "Synaptic modifications in the medial prefrontal cortex in susceptibility and resilience to stress". The Journal of Neuroscience. 34 (22): 7485–7492. doi:10.1523/JNEUROSCI.5294-13.2014. PMC 4035514. PMID 24872553.
  27. ^ a b c 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.
  28. ^ Harz H, Hegemann P (1991-06-06). "Rhodopsin-regulated calcium currents in Chlamydomonas". Nature. 351 (6326): 489–491. Bibcode:1991Natur.351..489H. doi:10.1038/351489a0. S2CID 4309593.
  29. ^ Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM, Bamberg E, Hegemann P (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.
  30. ^ Deisseroth K (September 2015). "Optogenetics: 10 years of microbial opsins in neuroscience". Nature Neuroscience. 18 (9): 1213–1225. doi:10.1038/nn.4091. PMC 4790845. PMID 26308982.
  31. ^ 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.
  32. ^ "He may be the rightful inventor of neuroscience's biggest breakthrough in decades. But you've never heard of him". STAT. 1 September 2016. Retrieved 9 February 2020.
  33. ^ Deisseroth, Karl (26 August 2015). "Optogenetics: 10 years of microbial opsins in neuroscience". Nature Neuroscience. 18 (9): 1213–1225. doi:10.1038/nn.4091. PMC 4790845. PMID 26308982.
  34. ^ Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, Pan ZH (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.
  35. ^ 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. S2CID 14608546.
  36. ^ a b 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.
  37. ^ 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. S2CID 7036529.
  38. ^ Tsien JZ, Chen DF, Gerber D, Tom C, Mercer EH, Anderson DJ, et al. (December 1996). "Subregion- and cell type-restricted gene knockout in mouse brain". Cell. 87 (7): 1317–1326. doi:10.1016/S0092-8674(00)81826-7. PMID 8980237. S2CID 863399.
  39. ^ Tsien JZ (2016). "Cre-Lox Neurogenetics: 20 Years of Versatile Applications in Brain Research and Counting..." Frontiers in Genetics. 7: 19. doi:10.3389/fgene.2016.00019. PMC 4759636. PMID 26925095.
  40. ^ 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). Public Library of Science: e299. Bibcode:2007PLoSO...2..299H. doi:10.1371/journal.pone.0000299. OCLC 678618519. PMC 1808431. PMID 17375185.
  41. ^ 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.
  42. ^ Schröder-Lang S, Schwärzel M, Seifert R, Strünker T, Kateriya S, Looser J, et al. (January 2007). "Fast manipulation of cellular cAMP level by light in vivo". Nature Methods. 4 (1): 39–42. doi:10.1038/nmeth975. PMID 17128267. S2CID 10616442.
  43. ^ Gao S, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (September 2015). "Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp". Nature Communications. 6 (1): 8046. Bibcode:2015NatCo...6.8046G. doi:10.1038/ncomms9046. PMC 4569695. PMID 26345128.
  44. ^ a b c Baratta MV, Nakamura S, Dobelis P, Pomrenze MB, Dolzani SD, Cooper DC (2 April 2012). "Optogenetic control of genetically-targeted pyramidal neuron activity in prefrontal cortex" (PDF). Nature Precedings. arXiv:1204.0710. Bibcode:2012arXiv1204.0710B. doi:10.1038/npre.2012.7102.1. S2CID 31641314.
  45. ^ Husson SJ, Liewald JF, Schultheis C, Stirman JN, Lu H, Gottschalk A (2012). Samuel A (ed.). "Microbial light-activatable proton pumps as neuronal inhibitors to functionally dissect neuronal networks in C. elegans". PLOS ONE. 7 (7): e40937. Bibcode:2012PLoSO...740937H. doi:10.1371/journal.pone.0040937. PMC 3397962. PMID 22815873. Open access icon
  46. ^ Liu Y, LeBeouf B, Guo X, Correa PA, Gualberto DG, Lints R, Garcia LR (March 2011). Goodman MB (ed.). "A cholinergic-regulated circuit coordinates the maintenance and bi-stable states of a sensory-motor behavior during Caenorhabditis elegans male copulation". PLOS Genetics. 7 (3): e1001326. doi:10.1371/journal.pgen.1001326. PMC 3053324. PMID 21423722. Open access icon
  47. ^ Deisseroth K. "Optogenetics: Controlling the Brain with Light [Extended Version]". Scientific American. Retrieved 2016-11-28.
  48. ^ Beck S, Yu-Strzelczyk J, Pauls D, Constantin OM, Gee CE, Ehmann N, et al. (2018). "Synthetic Light-Activated Ion Channels for Optogenetic Activation and Inhibition". Frontiers in Neuroscience. 12: 643. doi:10.3389/fnins.2018.00643. PMC 6176052. PMID 30333716.
  49. ^ Sierra YA, Rost B, Oldani S, Schneider-Warme F, Seifert R, Schmitz D, Hegemann P (November 2018). "Potassium channel-based two component optogenetic tool for silencing of excitable cells". Biophysical Journal. 114 (3): 668a. Bibcode:2018BpJ...114..668A. doi:10.1016/j.bpj.2017.11.3607. hdl:21.11116/0000-0003-4AEF-E.
  50. ^ Zhao S, Cunha C, Zhang F, Liu Q, Gloss B, Deisseroth K, et al. (August 2008). "Improved expression of halorhodopsin for light-induced silencing of neuronal activity". Brain Cell Biology. 36 (1–4): 141–154. doi:10.1007/s11068-008-9034-7. PMC 3057022. PMID 18931914.
  51. ^ a b Gradinaru V, Thompson KR, Deisseroth K (August 2008). "eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications". Brain Cell Biology. 36 (1–4): 129–139. doi:10.1007/s11068-008-9027-6. PMC 2588488. PMID 18677566.
  52. ^ a b c Witten IB, Lin SC, Brodsky M, Prakash R, Diester I, Anikeeva P, et al. (December 2010). "Cholinergic interneurons control local circuit activity and cocaine conditioning". Science. 330 (6011): 1677–1681. Bibcode:2010Sci...330.1677W. doi:10.1126/science.1193771. PMC 3142356. PMID 21164015.
  53. ^ Kim JM, Hwa J, Garriga P, Reeves PJ, RajBhandary UL, Khorana HG (February 2005). "Light-driven activation of beta 2-adrenergic receptor signaling by a chimeric rhodopsin containing the beta 2-adrenergic receptor cytoplasmic loops". Biochemistry. 44 (7): 2284–2292. doi:10.1021/bi048328i. PMID 15709741.
  54. ^ Airan RD, Thompson KR, Fenno LE, Bernstein H, Deisseroth K (April 2009). "Temporally precise in vivo control of intracellular signalling". Nature. 458 (7241): 1025–1029. Bibcode:2009Natur.458.1025A. doi:10.1038/nature07926. PMID 19295515. S2CID 4401796.
  55. ^ Levskaya A, Weiner OD, Lim WA, Voigt CA (October 2009). "Spatiotemporal control of cell signalling using a light-switchable protein interaction". Nature. 461 (7266): 997–1001. Bibcode:2009Natur.461..997L. doi:10.1038/nature08446. PMC 2989900. PMID 19749742.
  56. ^ Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM (September 2009). "A genetically encoded photoactivatable Rac controls the motility of living cells". Nature. 461 (7260): 104–108. Bibcode:2009Natur.461..104W. doi:10.1038/nature08241. PMC 2766670. PMID 19693014.
  57. ^ Yazawa M, Sadaghiani AM, Hsueh B, Dolmetsch RE (October 2009). "Induction of protein-protein interactions in live cells using light". Nature Biotechnology. 27 (10): 941–945. doi:10.1038/nbt.1569. PMID 19801976. S2CID 205274357.
  58. ^ Stierl M, Stumpf P, Udwari D, Gueta R, Hagedorn R, Losi A, et al. (January 2011). "Light modulation of cellular cAMP by a small bacterial photoactivated adenylyl cyclase, bPAC, of the soil bacterium Beggiatoa". The Journal of Biological Chemistry. 286 (2): 1181–1188. doi:10.1074/jbc.M110.185496. PMC 3020725. PMID 21030594.
  59. ^ Ryu MH, Moskvin OV, Siltberg-Liberles J, Gomelsky M (December 2010). "Natural and engineered photoactivated nucleotidyl cyclases for optogenetic applications". The Journal of Biological Chemistry. 285 (53): 41501–41508. doi:10.1074/jbc.M110.177600. PMC 3009876. PMID 21030591.
  60. ^ Lerner TN, Ye L, Deisseroth K (March 2016). "Communication in Neural Circuits: Tools, Opportunities, and Challenges". Cell. 164 (6): 1136–1150. doi:10.1016/j.cell.2016.02.027. PMC 5725393. PMID 26967281.
  61. ^ Aravanis AM, Wang LP, Zhang F, Meltzer LA, Mogri MZ, Schneider MB, Deisseroth K (September 2007). "An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology". Journal of Neural Engineering. 4 (3): S143–S156. Bibcode:2007JNEng...4S.143A. doi:10.1088/1741-2560/4/3/S02. PMID 17873414. S2CID 1488394.
  62. ^ 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.
  63. ^ a b Gradinaru V, Thompson KR, Zhang F, Mogri M, Kay K, Schneider MB, Deisseroth K (December 2007). "Targeting and readout strategies for fast optical neural control in vitro and in vivo". The Journal of Neuroscience. 27 (52): 14231–14238. doi:10.1523/JNEUROSCI.3578-07.2007. PMC 6673457. PMID 18160630.
  64. ^ Damestani Y, Reynolds CL, Szu J, Hsu MS, Kodera Y, Binder DK, et al. (November 2013). "Transparent nanocrystalline yttria-stabilized-zirconia calvarium prosthesis". Nanomedicine. 9 (8): 1135–1138. doi:10.1016/j.nano.2013.08.002. PMID 23969102. S2CID 14212180. • Explained by Mohan G (September 4, 2013). "A window to the brain? It's here, says UC Riverside team". Los Angeles Times.
  65. ^ a b Legaria AA, Matikainen-Ankney BA, Yang B, Ahanonu B, Licholai JA, Parker JG, Kravitz AV (August 30, 2022). "Fiber photometry in striatum reflects primarily nonsomatic changes in calcium". Nature Neuroscience. 25 (9): 1124–1128. doi:10.1038/s41593-022-01152-z. PMC 10152879. PMID 36042311.
  66. ^ Wentz CT, Bernstein JG, Monahan P, Guerra A, Rodriguez A, Boyden ES (August 2011). "A wirelessly powered and controlled device for optical neural control of freely-behaving animals". Journal of Neural Engineering. 8 (4): 046021. Bibcode:2011JNEng...8d6021W. doi:10.1088/1741-2560/8/4/046021. PMC 3151576. PMID 21701058.
  67. ^ Pama EA, Colzato LS, Hommel B (2013-01-01). "Optogenetics as a neuromodulation tool in cognitive neuroscience". Frontiers in Psychology. 4: 610. doi:10.3389/fpsyg.2013.00610. PMC 3764402. PMID 24046763.
  68. ^ Vierock, Johannes; Rodriguez-Rozada, Silvia; Dieter, Alexander; Pieper, Florian; Sims, Ruth; Tenedini, Federico; Bergs, Amelie C. F.; Bendifallah, Imane; Zhou, Fangmin; Zeitzschel, Nadja; Ahlbeck, Joachim (2021-07-26). "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. ISSN 2041-1723. PMC 8313717. PMID 34312384.
  69. ^ Zhang F, Gradinaru V, Adamantidis AR, Durand R, Airan RD, de Lecea L, Deisseroth K (March 2010). "Optogenetic interrogation of neural circuits: technology for probing mammalian brain structures". Nature Protocols. 5 (3): 439–456. doi:10.1038/nprot.2009.226. PMC 4503465. PMID 20203662.
  70. ^ Zeng H, Madisen L (2012-09-05). "Mouse transgenic approaches in optogenetics". Optogenetics: Tools for Controlling and Monitoring Neuronal Activity. Progress in Brain Research. Vol. 196. pp. 193–213. doi:10.1016/B978-0-444-59426-6.00010-0. ISBN 9780444594266. PMC 3433654. PMID 22341327.
  71. ^ Warden MR, Cardin JA, Deisseroth K (July 2014). "Optical neural interfaces". Annual Review of Biomedical Engineering. 16: 103–129. doi:10.1146/annurev-bioeng-071813-104733. PMC 4163158. PMID 25014785.
  72. ^ Guru A, Post RJ, Ho YY, Warden MR (July 2015). "Making Sense of Optogenetics". The International Journal of Neuropsychopharmacology. 18 (11): pyv079. doi:10.1093/ijnp/pyv079. PMC 4756725. PMID 26209858.
  73. ^ "The Evolution in Freely-Behaving Imaging and Optogenetics Technology". OASIS Implant. Mightex. Retrieved 2021-06-03.
  74. ^ Cui G, Jun SB, Jin X, Luo G, Pham MD, Lovinger DM, et al. (April 2016). "Deep brain optical measurements of cell type-specific neural activity in behaving mice". Nature Protocols. 9 (6): 1213–1228. doi:10.1038/nmeth.3770. PMC 4100551. PMID 24784819.
  75. ^ Cui G, Jun SB, Jin X, Luo G, Pham MD, Lovinger DM, et al. (June 2014). "Deep brain optical measurements of cell type-specific neural activity in behaving mice". Nature Protocols. 9 (6): 1213–1228. doi:10.1038/nprot.2014.080. PMC 4100551. PMID 24784819.
  76. ^ a b c d Zalocusky KA, Fenno LE, Deisseroth K (2013). "Current Challenges in Optogenetics". Society for Neuroscience.
  77. ^ Heitmann S, Rule M, Truccolo W, Ermentrout B (January 2017). "Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type I to Type II: Oscillation Onset and Wave Propagation". PLOS Computational Biology. 13 (1): e1005349. Bibcode:2017PLSCB..13E5349H. doi:10.1371/journal.pcbi.1005349. PMC 5295702. PMID 28118355.
  78. ^ Zhang, Yan-Ping; Oertner, Thomas G (2007). "Optical induction of synaptic plasticity using a light-sensitive channel". Nature Methods. 4 (2): 139–141. doi:10.1038/nmeth988. ISSN 1548-7091. PMID 17195846. S2CID 17721823.
  79. ^ Leergaard TB, Hilgetag CC, Sporns O (2012-05-01). "Mapping the connectome: multi-level analysis of brain connectivity". Frontiers in Neuroinformatics. 6: 14. doi:10.3389/fninf.2012.00014. PMC 3340894. PMID 22557964.
  80. ^ a b Luboeinski J, Tchumatchenko T (September 2020). "Nonlinear response characteristics of neural networks and single neurons undergoing optogenetic excitation". Network Neuroscience. 4 (3): 852–870. doi:10.1162/netn_a_00154. PMC 7888483. PMID 33615093.
  81. ^ "PyRhO: a virtual optogenetics laboratory". GitHub.
  82. ^ "Simulation tool for neural networks and single neurons with light-sensitive channels". GitHub.
  83. ^ Azees, Ajmal (December 2023). "Spread of activation and interaction between channels with multi-channel optogenetic stimulation in the mouse cochlea". Hearing Research. 440. doi:10.1016/j.heares.2023.108911. PMID 37977051.
  84. ^ Kravitz AV, Freeze BS, Parker PR, Kay K, Thwin MT, Deisseroth K, Kreitzer AC (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.
  85. ^ 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.
  86. ^ Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, Deisseroth K, et al. (June 2009). "Driving fast-spiking cells induces gamma rhythm and controls sensory responses". Nature. 459 (7247): 663–667. Bibcode:2009Natur.459..663C. doi:10.1038/nature08002. PMC 3655711. PMID 19396156.
  87. ^ Sohal VS, Zhang F, Yizhar O, Deisseroth K (June 2009). "Parvalbumin neurons and gamma rhythms enhance cortical circuit performance". Nature. 459 (7247): 698–702. Bibcode:2009Natur.459..698S. doi:10.1038/nature07991. PMC 3969859. PMID 19396159.
  88. ^ Tsai HC, Zhang F, Adamantidis A, Stuber GD, Bonci A, de Lecea L, Deisseroth K (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.
  89. ^ Zimmer C (24 May 2021). "Scientists Partially Restored a Blind Man's Sight With New Gene Therapy". The New York Times. Retrieved 25 May 2021.
  90. ^ Haubensak W, Kunwar PS, Cai H, Ciocchi S, Wall NR, Ponnusamy R, et al. (November 2010). "Genetic dissection of an amygdala microcircuit that gates conditioned fear". Nature. 468 (7321): 270–276. Bibcode:2010Natur.468..270H. doi:10.1038/nature09553. PMC 3597095. PMID 21068836.
  91. ^ Johansen JP, Hamanaka H, Monfils MH, Behnia R, Deisseroth K, Blair HT, LeDoux JE (July 2010). "Optical activation of lateral amygdala pyramidal cells instructs associative fear learning". Proceedings of the National Academy of Sciences of the United States of America. 107 (28): 12692–12697. Bibcode:2010PNAS..10712692J. doi:10.1073/pnas.1002418107. PMC 2906568. PMID 20615999.
  92. ^ Jasnow AM, Ehrlich DE, Choi DC, Dabrowska J, Bowers ME, McCullough KM, et al. (June 2013). "Thy1-expressing neurons in the basolateral amygdala may mediate fear inhibition". The Journal of Neuroscience. 33 (25): 10396–10404. doi:10.1523/JNEUROSCI.5539-12.2013. PMC 3685835. PMID 23785152.
  93. ^ Dias BG, Banerjee SB, Goodman JV, Ressler KJ (June 2013). "Towards new approaches to disorders of fear and anxiety". Current Opinion in Neurobiology. 23 (3): 346–352. doi:10.1016/j.conb.2013.01.013. PMC 3672317. PMID 23402950.
  94. ^ Karalis N, Dejean C, Chaudun F, Khoder S, Rozeske RR, Wurtz H, et al. (April 2016). "4-Hz oscillations synchronize prefrontal-amygdala circuits during fear behavior". Nature Neuroscience. 19 (4): 605–612. doi:10.1038/nn.4251. PMC 4843971. PMID 26878674.
  95. ^ Shusterman R, Smear MC, Koulakov AA, Rinberg D (July 2011). "Precise olfactory responses tile the sniff cycle". Nature Neuroscience. 14 (8): 1039–1044. doi:10.1038/nn.2877. PMID 21765422. S2CID 5194595.
  96. ^ Smith RS, Hu R, DeSouza A, Eberly CL, Krahe K, Chan W, Araneda RC (July 2015). "Differential Muscarinic Modulation in the Olfactory Bulb". The Journal of Neuroscience. 35 (30): 10773–10785. doi:10.1523/JNEUROSCI.0099-15.2015. PMC 4518052. PMID 26224860.
  97. ^ Patterson MA, Lagier S, Carleton A (August 2013). "Odor representations in the olfactory bulb evolve after the first breath and persist as an odor afterimage". Proceedings of the National Academy of Sciences of the United States of America. 110 (35): E3340–E3349. Bibcode:2013PNAS..110E3340P. doi:10.1073/pnas.1303873110. PMC 3761593. PMID 23918364.
  98. ^ Tecuapetla F, Patel JC, Xenias H, English D, Tadros I, Shah F, et al. (May 2010). "Glutamatergic signaling by mesolimbic dopamine neurons in the nucleus accumbens". The Journal of Neuroscience. 30 (20): 7105–7110. doi:10.1523/JNEUROSCI.0265-10.2010. PMC 3842465. PMID 20484653.
  99. ^ Cela E, McFarlan AR, Chung AJ, Wang T, Chierzi S, Murai KK, Sjöström PJ (March 2019). "An Optogenetic Kindling Model of Neocortical Epilepsy". Scientific Reports. 9 (1): 5236. Bibcode:2019NatSR...9.5236C. doi:10.1038/s41598-019-41533-2. PMC 6437216. PMID 30918286.
  100. ^ a b Ryu B, Nagappan S, Santos-Valencia F, Lee P, Rodriguez E, Lackie M, et al. (April 2021). "Chronic loss of inhibition in piriform cortex following brief, daily optogenetic stimulation". Cell Reports. 35 (3): 109001. doi:10.1016/j.celrep.2021.109001. PMC 8102022. PMID 33882304.
  101. ^ Bingen BO, Engels MC, Schalij MJ, Jangsangthong W, Neshati Z, Feola I, et al. (October 2014). "Light-induced termination of spiral wave arrhythmias by optogenetic engineering of atrial cardiomyocytes". Cardiovascular Research. 104 (1): 194–205. doi:10.1093/cvr/cvu179. PMID 25082848.
  102. ^ Nussinovitch U, Gepstein L (July 2015). "Optogenetics for in vivo cardiac pacing and resynchronization therapies". Nature Biotechnology. 33 (7): 750–754. doi:10.1038/nbt.3268. PMID 26098449. S2CID 1794556.
  103. ^ Nyns EC, Kip A, Bart CI, Plomp JJ, Zeppenfeld K, Schalij MJ, et al. (July 2017). "Optogenetic termination of ventricular arrhythmias in the whole heart: towards biological cardiac rhythm management". European Heart Journal. 38 (27): 2132–2136. doi:10.1093/eurheartj/ehw574. PMC 5837774. PMID 28011703.
  104. ^ Bruegmann T, Boyle PM, Vogt CC, Karathanos TV, Arevalo HJ, Fleischmann BK, et al. (October 2016). "Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations". The Journal of Clinical Investigation. 126 (10): 3894–3904. doi:10.1172/JCI88950. PMC 5096832. PMID 27617859.
  105. ^ Crocini C, Ferrantini C, Coppini R, Scardigli M, Yan P, Loew LM, et al. (October 2016). "Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation". Scientific Reports. 6: 35628. Bibcode:2016NatSR...635628C. doi:10.1038/srep35628. PMC 5066272. PMID 27748433.
  106. ^ 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.
  107. ^ 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.
  108. ^ 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.
  109. ^ "Engineering long-wavelength light-driven ion channels to hear the light. Atlas of Science". Retrieved 7 November 2019.
  110. ^ Moser T (October 2015). "Optogenetic stimulation of the auditory pathway for research and future prosthetics". Current Opinion in Neurobiology. 34: 29–36. doi:10.1016/j.conb.2015.01.004. PMID 25637880. S2CID 35199775.
  111. ^ 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.
  112. ^ Matthews GA, Nieh EH, Vander Weele CM, Halbert SA, Pradhan RV, Yosafat AS, et al. (February 2016). "Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation". Cell. 164 (4): 617–631. doi:10.1016/j.cell.2015.12.040. PMC 4752823. PMID 26871628.
  113. ^ 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.
  114. ^ 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.
  115. ^ 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. doi:10.1126/science.aaa7484. PMC 4764398. PMID 26113638.
  116. ^ Mauss AS, Busch C, Borst A (October 2017). "Optogenetic Neuronal Silencing in Drosophila during Visual Processing". Scientific Reports. 7 (1): 13823. Bibcode:2017NatSR...713823M. doi:10.1038/s41598-017-14076-7. PMC 5653863. PMID 29061981.
  117. ^ Portugues, Ruben; Severi, Kristen E; Wyart, Claire; Ahrens, Misha B (2013-02-01). "Optogenetics in a transparent animal: circuit function in the larval zebrafish". Current Opinion in Neurobiology. Neurogenetics. 23 (1): 119–126. doi:10.1016/j.conb.2012.11.001. ISSN 0959-4388. PMID 23246238. S2CID 19906279.
  118. ^ Cande, Jessica; Namiki, Shigehiro; Qiu, Jirui; Korff, Wyatt; Card, Gwyneth M; Shaevitz, Joshua W; Stern, David L; Berman, Gordon J (2018-06-26). Scott, Kristin (ed.). "Optogenetic dissection of descending behavioral control in Drosophila". eLife. 7: e34275. doi:10.7554/eLife.34275. ISSN 2050-084X. PMC 6031430. PMID 29943729.
  119. ^ DeAngelis, Brian D; Zavatone-Veth, Jacob A; Gonzalez-Suarez, Aneysis D; Clark, Damon A (2020-04-22). Calabrese, Ronald L (ed.). "Spatiotemporally precise optogenetic activation of sensory neurons in freely walking Drosophila". eLife. 9: e54183. doi:10.7554/eLife.54183. ISSN 2050-084X. PMC 7198233. PMID 32319425.
  120. ^ Bidaye, Salil S.; Laturney, Meghan; Chang, Amy K.; Liu, Yuejiang; Bockemühl, Till; Büschges, Ansgar; Scott, Kristin (2020-11-11). "Two Brain Pathways Initiate Distinct Forward Walking Programs in Drosophila". Neuron. 108 (3): 469–485.e8. doi:10.1016/j.neuron.2020.07.032. ISSN 0896-6273. PMC 9435592. PMID 32822613. S2CID 221198570.
  121. ^ Heiney, Shane A.; Kim, Jinsook; Augustine, George J.; Medina, Javier F. (2014-02-05). "Precise Control of Movement Kinematics by Optogenetic Inhibition of Purkinje Cell Activity". Journal of Neuroscience. 34 (6): 2321–2330. doi:10.1523/JNEUROSCI.4547-13.2014. ISSN 0270-6474. PMC 3913874. PMID 24501371.
  122. ^ Solari N, Sviatkó K, Laszlovszky T, Hegedüs P, Hangya B (May 2018). "Open Source Tools for Temporally Controlled Rodent Behavior Suitable for Electrophysiology and Optogenetic Manipulations". Frontiers in Systems Neuroscience. 12: 18. doi:10.3389/fnsys.2018.00018. PMC 5962774. PMID 29867383.
  123. ^ 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.
  124. ^ Grosenick, Logan; Marshel, James H.; Deisseroth, Karl (2015-04-08). "Closed-Loop and Activity-Guided Optogenetic Control". Neuron. 86 (1): 106–139. doi:10.1016/j.neuron.2015.03.034. ISSN 0896-6273. PMC 4775736. PMID 25856490.
  125. ^ Armstrong, Caren; Krook-Magnuson, Esther; Oijala, Mikko; Soltesz, Ivan (2013). "Closed-loop optogenetic intervention in mice". Nature Protocols. 8 (8): 1475–1493. doi:10.1038/nprot.2013.080. ISSN 1750-2799. PMC 3988315. PMID 23845961.
  126. ^ Kovács KA, O'Neill J, Schoenenberger P, Penttonen M, Ranguel Guerrero DK, Csicsvari J (19 Nov 2016). "Optogenetically Blocking Sharp Wave Ripple Events in Sleep Does Not Interfere with the Formation of Stable Spatial Representation in the CA1 Area of the Hippocampus". PLOS ONE. 11 (10): e0164675. Bibcode:2016PLoSO..1164675K. doi:10.1371/journal.pone.0164675. PMC 5070819. PMID 27760158.
  127. ^ a b Valon L, Marín-Llauradó A, Wyatt T, Charras G, Trepat X (February 2017). "Optogenetic control of cellular forces and mechanotransduction". Nature Communications. 8: 14396. Bibcode:2017NatCo...814396V. doi:10.1038/ncomms14396. PMC 5309899. PMID 28186127.
  128. ^ a b c d e Khamo JS, Krishnamurthy VV, Sharum SR, Mondal P, Zhang K (October 2017). "Applications of Optobiology in Intact Cells and Multicellular Organisms". Journal of Molecular Biology. 429 (20): 2999–3017. doi:10.1016/j.jmb.2017.08.015. PMID 28882542.
  129. ^ Fenno L, Yizhar O, Deisseroth K (2011). "The development and application of optogenetics". Annual Review of Neuroscience. 34: 389–412. doi:10.1146/annurev-neuro-061010-113817. PMC 6699620. PMID 21692661.
  130. ^ "Method of the Year 2010: Optogenetics". Nature Video. 17 December 2010.
  131. ^ "optogenetics - Search Results". PubMed. Retrieved 2020-02-29.
  132. ^ Wittmann T, Dema A, van Haren J (October 2020). "Lights, cytoskeleton, action: Optogenetic control of cell dynamics". Current Opinion in Cell Biology. 66. Elsevier Ltd.: 1–10. doi:10.1016/j.ceb.2020.03.003. PMC 7577957. PMID 32371345.
  133. ^ Konermann S, Brigham MD, Trevino A, Hsu PD, Heidenreich M, Cong L, et al. (August 2013). "Optical control of mammalian endogenous transcription and epigenetic states". Nature. 500 (7463): 472–476. Bibcode:2013Natur.500..472K. doi:10.1038/nature12466. PMC 3856241. PMID 23877069.
  134. ^ Leung DW, Otomo C, Chory J, Rosen MK (September 2008). "Genetically encoded photoswitching of actin assembly through the Cdc42-WASP-Arp2/3 complex pathway". Proceedings of the National Academy of Sciences of the United States of America. 105 (35): 12797–12802. Bibcode:2008PNAS..10512797L. doi:10.1073/pnas.0801232105. PMC 2525560. PMID 18728185.
  135. ^ Toettcher JE, Gong D, Lim WA, Weiner OD (September 2011). "Light-based feedback for controlling intracellular signaling dynamics". Nature Methods. 8 (10): 837–839. doi:10.1038/nmeth.1700. PMC 3184382. PMID 21909100.
  136. ^ Strickland D, Lin Y, Wagner E, Hope CM, Zayner J, Antoniou C, et al. (March 2012). "TULIPs: tunable, light-controlled interacting protein tags for cell biology". Nature Methods. 9 (4): 379–384. doi:10.1038/nmeth.1904. PMC 3444151. PMID 22388287.
  137. ^ Idevall-Hagren O, Dickson EJ, Hille B, Toomre DK, De Camilli P (August 2012). "Optogenetic control of phosphoinositide metabolism". Proceedings of the National Academy of Sciences of the United States of America. 109 (35): E2316–E2323. Bibcode:2012PNAS..109E2316I. doi:10.1073/pnas.1211305109. PMC 3435206. PMID 22847441.
  138. ^ Bugaj LJ, Choksi AT, Mesuda CK, Kane RS, Schaffer DV (March 2013). "Optogenetic protein clustering and signaling activation in mammalian cells". Nature Methods. 10 (3): 249–252. doi:10.1038/nmeth.2360. PMID 23377377. S2CID 8737019.
  139. ^ Lungu OI, Hallett RA, Choi EJ, Aiken MJ, Hahn KM, Kuhlman B (April 2012). "Designing photoswitchable peptides using the AsLOV2 domain". Chemistry & Biology. 19 (4): 507–517. doi:10.1016/j.chembiol.2012.02.006. PMC 3334866. PMID 22520757.
  140. ^ Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM (September 2009). "A genetically encoded photoactivatable Rac controls the motility of living cells". Nature. 461 (7260): 104–108. Bibcode:2009Natur.461..104W. doi:10.1038/nature08241. PMC 2766670. PMID 19693014.
  141. ^ Smart AD, Pache RA, Thomsen ND, Kortemme T, Davis GW, Wells JA (September 2017). "Engineering a light-activated caspase-3 for precise ablation of neurons in vivo". Proceedings of the National Academy of Sciences of the United States of America. 114 (39): E8174–E8183. Bibcode:2017PNAS..114E8174S. doi:10.1073/pnas.1705064114. PMC 5625904. PMID 28893998.
  142. ^ Dagliyan O, Tarnawski M, Chu PH, Shirvanyants D, Schlichting I, Dokholyan NV, Hahn KM (December 2016). "Engineering extrinsic disorder to control protein activity in living cells". Science. 354 (6318): 1441–1444. Bibcode:2016Sci...354.1441D. doi:10.1126/science.aah3404. PMC 5362825. PMID 27980211.
  143. ^ Guntas G, Hallett RA, Zimmerman SP, Williams T, Yumerefendi H, Bear JE, Kuhlman B (January 2015). "Engineering an improved light-induced dimer (iLID) for controlling the localization and activity of signaling proteins". Proceedings of the National Academy of Sciences of the United States of America. 112 (1): 112–117. Bibcode:2015PNAS..112..112G. doi:10.1073/pnas.1417910112. PMC 4291625. PMID 25535392.
  144. ^ Wang H, Vilela M, Winkler A, Tarnawski M, Schlichting I, Yumerefendi H, et al. (September 2016). "LOVTRAP: an optogenetic system for photoinduced protein dissociation". Nature Methods. 13 (9): 755–758. doi:10.1038/nmeth.3926. PMC 5137947. PMID 27427858.
  145. ^ van Haren J, Charafeddine RA, Ettinger A, Wang H, Hahn KM, Wittmann T (March 2018). "Local control of intracellular microtubule dynamics by EB1 photodissociation". Nature Cell Biology. 20 (3). Nature Research.: 252–261. doi:10.1038/s41556-017-0028-5. PMC 5826794. PMID 29379139.
  146. ^ a b Zhou XX, Chung HK, Lam AJ, Lin MZ (November 2012). "Optical control of protein activity by fluorescent protein domains". Science. 338 (6108): 810–814. Bibcode:2012Sci...338..810Z. doi:10.1126/science.1226854. PMC 3702057. PMID 23139335.
  147. ^ Tischer D, Weiner OD (August 2014). "Illuminating cell signalling with optogenetic tools". Nature Reviews. Molecular Cell Biology. 15 (8): 551–558. doi:10.1038/nrm3837. PMC 4145075. PMID 25027655.
  148. ^ Purvis JE, Lahav G (February 2013). "Encoding and decoding cellular information through signaling dynamics". Cell. 152 (5): 945–956. doi:10.1016/j.cell.2013.02.005. PMC 3707615. PMID 23452846.
  149. ^ Santos SD, Verveer PJ, Bastiaens PI (March 2007). "Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate". Nature Cell Biology. 9 (3): 324–330. doi:10.1038/ncb1543. PMID 17310240. S2CID 31709706.
  150. ^ Toettcher JE, Weiner OD, Lim WA (December 2013). "Using optogenetics to interrogate the dynamic control of signal transmission by the Ras/Erk module". Cell. 155 (6): 1422–1434. doi:10.1016/j.cell.2013.11.004. PMC 3925772. PMID 24315106.
  151. ^ Huidobro N, Mendez-Fernandez A, Mendez-Balbuena I, Gutierrez R, Kristeva R, Manjarrez E (2017). "Brownian Optogenetic-Noise-Photostimulation on the Brain Amplifies Somatosensory-Evoked Field Potentials". Frontiers in Neuroscience. 11: 464. doi:10.3389/fnins.2017.00464. PMC 5583167. PMID 28912671.
  152. ^ Huidobro N, De la Torre-Valdovinos B, Mendez A, Treviño M, Arias-Carrion O, Chavez F, et al. (January 2018). "Optogenetic noise-photostimulation on the brain increases somatosensory spike firing responses". Neuroscience Letters. 664: 51–57. doi:10.1016/j.neulet.2017.11.004. PMID 29128628. S2CID 3370851.
  153. ^ Mabil P, Huidobro N, Torres-Ramirez O, Flores-Hernandez J, Flores A, Gutierrez R, Manjarrez E (2020). "Noisy Light Augments the Na+ Current in Somatosensory Pyramidal Neurons of Optogenetic Transgenic Mice". Frontiers in Neuroscience. 14: 490. doi:10.3389/fnins.2020.00490. PMC 7263390. PMID 32528244.
  154. ^ Ninth Annual Wiley Prize in Biomedical Sciences Awarded to Dr. Peter Hegemann, Dr. Georg Nagel, and Dr. Ernst Bamberg (wiley.com)
  155. ^ "Karl Heinz Beckurts-Preis 2010". Karl Heinz Beckurts Foundation.
  156. ^ "HFSP Nakasone Award 2010". Human Frontier Science Program.
  157. ^ "International Prize for Translational Neuroscience of the Gertrud Reemtsma Foundation (K.J. Zülch Prize until 2019)". Max Planck Society.
  158. ^ "InBev-Baillet Latour International Health Prize" (PDF). Fonds de la Recherche Scientifique - FNRS.
  159. ^ Louis-Jeantet Prize
  160. ^ "The Brain Prize 2013". Archived from the original on 4 October 2013. Retrieved 3 October 2013.
  161. ^ 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.
  162. ^ "Else Kröner Fresenius Prize for Medical Research 2017". Else Kröner-Fresenius Foundation.
  163. ^ "2018 Kyoto Prize Laureate Karl Deisseroth". Kyoto Prize.
  164. ^ "Rumford Prize Awarded for the Invention and Refinement of Optogenetics". American Academy of Arts & Sciences. 30 January 2019. Retrieved 2019-03-12.
  165. ^ "2020 Heineken Prize Laureate Karl Deisseroth". Heineken Prizes.
  166. ^ "2020 Shaw Prize Laureates Miesenböck, Hegemann and Georg Nagel". Shaw Prize.

Further reading

[edit]
[edit]
Look up optogenetics in Wiktionary, the free dictionary.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Optogenetics&oldid=1260327182"