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Introduction
Published in Shoogo Ueno, Bioimaging, 2020
Karl Deisseroth (1971–) in the USA and his group published a paper on millisecond-timescale, genetically targeted optical control of neural activity, and demonstrated millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission in 2005 (Boyden et al., 2005). They adapted the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photo-stimulate mammalian neurons. Deisseroth appeals that this technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers. Thus, Deisseroth has spearheaded “optogenetics,” a new methodological discipline in which cellular activities are controlled by light and has revolutionized systems neuroscience research.
Experimental models and measurements to study cardiovascular physiology
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
Another method for the electrical stimulation of isolated cells, or individual/groups of cells in multicellular preparations or in vivo is optogenetics. This technique, developed by the Miesenbock group in the early 2000s, involves expressing genetically modified, light-sensitive ion channels known as channelrhodopsins in a cell of interest. The expression of these ion channels can be linked to cell-specific promoters in multicellular tissue, and combined with a fibre-optic, solid state light source for illumination. This allows the stimulation of either an individual cell or groups of cells with millisecond temporal precision, without the need for microelectrodes. The technique has been widely used to study neurons and neuronal circuits in vitro and in vivo in the central nervous system, but is equally applicable to other excitable cells such as cardiac myocytes.
Neurophotonics for Peripheral Nerves
Published in Yu Chen, Babak Kateb, Neurophotonics and Brain Mapping, 2017
Ashfaq Ahmed, Yuqiang Bai, Jessica C. Ramella-Roman, Ranu Jung
So far, optogenetics has been used to great effect in the brain (Yizhar et al., 2011). Its application in the PNS has been limited to a few studies (Wang and Zylka, 2009; Llewellyn et al., 2010; Sharp and Fromherz, 2011; Ji et al., 2012; Liske et al., 2013). It has been used to both activate (Llewellyn et al., 2010) and inhibit (Liske et al., 2013) motor neuron axons in anesthetized transgenic mice. Channelrhodopsin-2 has been used to excite neurons by depolarization. Halorhodopsin, which responds to light near 580 nm is used to inhibit excitation of neurons by hyperpolarization (Zhang et al., 2007b; Gradinaru et al., 2010). Optogenetic approaches have also been utilized to further our understanding of neural disorders (Tye and Deisseroth, 2012), neural systems, and encoding (Monesson-Olson et al., 2014). Recently optogenetic approaches have been proposed for the cure of blindness and Parkinson’s disease (Gradinaru et al., 2009; Kramer et al., 2009; Carter and de Lecea, 2011).
From leptin to lasers: the past and present of mouse models of obesity
Published in Expert Opinion on Drug Discovery, 2021
Joshua R. Barton, Adam E. Snook, Scott A. Waldman
DBS, like ablation studies, lacks the specificity to target specific neuronal subtypes. To simulate particular neuronal populations, the Cre-lox system had to be adapted to express modulatory receptors controlled by cell-type-specific Cre drivers. Ideally, these modulatory receptors would be responsive only to external stimuli applied by the experimenter, to eliminate confounding endogenous signaling from the mice. Studies on the phototaxis responses of the green algae Chlamydomanas reinhardtii revealed a unique class of opsin-related proteins called channelrhodopsins that produced light-gated ion conductance in the eye spot of these organisms [128]. When packaged into a lentiviral vector, Channelrhodopsin-2 (ChR2) evoked blue-light-dependent spike chains in rat hippocampal neurons in vitro, establishing channelrhodopsins as a tool for selectively stimulating rodent neurons [129].168
Preclinical stress research: where are we headed? An early career investigator’s perspective
Published in Stress, 2018
Anand Gururajan, Aron Kos, Juan Pablo Lopez
Recent developments in what is generally referred to as activity driven labeling of neuronal populations have opened up new avenues to dissect neural ensembles and mapping them in greater detail. More importantly, it has allowed researchers to access and manipulate these previously activated cell populations. A number of distinct labeling tools have been developed with varying properties in terms of specificity, signal to noise ratio and temporal activation. Central to most of the current available tools is the following observation that neural activity ultimately results in the expression of a number of immediate early genes (IEGs) (Guzowski, Setlow, Wagner, & McGaugh, 2001). By extracting promoter or enhancer sequences that drive the expression of IEGs and allowing them to control the expression of fluorescent reporters, opsins or other effector genes enables for permanent labeling of a previously transiently activated neuron. Some of the most widely used activity-dependent IEG promoter sequences are those of the Fos and Arc genes. An example of one of the possible applications of this technique was presented in a series of studies in which channelrhodopsin-2 expression was driven by c-fos activation (Liu et al., 2012; Ramirez et al., 2013; Redondo et al., 2014). Using this setup Ramirez et al. showed that optogenetic reactivation of a neural network associated with a positive experience within the hippocampus–amygdala–nucleus accumbens results in the suppression of depression-like behaviors induced by an acute stressor (Ramirez et al., 2015).
Every nano-step counts: a critical reflection on do’s and don’ts in researching nanomedicines for retinal gene therapy
Published in Expert Opinion on Drug Delivery, 2023
Karen Peynshaert, Joke Devoldere, Stefaan De Smedt, Katrien Remaut
One such strategy is optogenetics where genes encoding for light-sensitive proteins are introduced into retinal neurons with the aim to let them take over the role of the lost photoreceptors[19]. The most widely investigated optogenetic proteins are variants of channelrhodopsin, a light-gated ion channel that initiates cell depolarization when triggered. Potential cell types targeted by this strategy reside in the inner retinal layers and include ganglion cells and bipolar cells. Interestingly, since the optogenetic approach does not require viable PRs, this strategy could be used to treat patients in advanced stages of retinal degeneration [20,21]. Following successful studies in non-human primates [22,23], several clinical trials are now underway[7].