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Channelrhodopsin

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https://www.readbyqxmd.com/read/29643766/spatiotemporal-control-of-gpr37-signaling-and-its-behavioral-effects-by-optogenetics
#1
Wu Zheng, Jianhong Zhou, Yanan Luan, Jianglan Yang, Yuanyuan Ge, Muran Wang, Beibei Wu, Zhongnan Wu, Xingjun Chen, Fei Li, Zhihui Li, Sergii Vakal, Wei Guo, Jiang-Fan Chen
Despite the progress in deorphanization of G Protein-Coupled Receptors (GPCRs), ≈100 GPCRs are still classified as orphan receptors without identified endogenous ligands and with unknown physiological functions. The lack of endogenous ligands triggering GPCR signaling has hampered the study of orphan GPCR functions. Using GPR37 as an example, we provide here the first demonstration of the channelrhodopsin 2 (ChR2)-GPCR approach to bypass the endogenous ligand and selectively activate the orphan GPCR signal by optogenetics...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29625451/a-robust-optomotor-assay-for-assessing-the-efficacy-of-optogenetic-tools-for-vision-restoration
#2
Qi Lu, Tushar H Ganjawala, Samer Hattar, Gary W Abrams, Zhuo-Hua Pan
Purpose: To develop an animal behavioral assay for the quantitative assessment of the functional efficacy of optogenetic therapies. Methods: A triple-knockout (TKO) mouse line, Gnat1-/-Cnga3-/-Opn4-/-, and a double-knockout mouse line, Gnat1-/-Cnga3-/-, were employed. The expression of channelrhodopsin-2 (ChR2) and its three more light-sensitive mutants, ChR2-L132C, ChR2-L132C/T159C, and ChR2-132C/T159S, in inner retinal neurons was achieved using rAAV2 vectors via intravitreal delivery...
March 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29623428/frontal-cortical-control-of-posterior-sensory-and-association-cortices-through-the-claustrum
#3
Michael G White, Brian N Mathur
The claustrum is a telencephalic gray matter nucleus that is richly interconnected with the neocortex. This structure subserves top-down executive functions that require frontal cortical control of posterior cortical regions. However, functional anatomical support for the claustrum allowing for long-range intercortical communication is lacking. To test this, we performed a channelrhodopsin-assisted long-circuit mapping strategy in mouse brain slices. We find that anterior cingulate cortex input to the claustrum is transiently amplified by claustrum neurons that, in turn, project to parietal association cortex or to primary and secondary visual cortices...
April 6, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29621487/a-hypothalamic-midbrain-pathway-essential-for-driving-maternal-behaviors
#4
Yi-Ya Fang, Takashi Yamaguchi, Soomin C Song, Nicolas X Tritsch, Dayu Lin
Maternal behaviors are essential for the survival of the young. Previous studies implicated the medial preoptic area (MPOA) as an important region for maternal behaviors, but details of the maternal circuit remain incompletely understood. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the MPOA as key mediators of pup approach and retrieval. Reversible inactivation of MPOAEsr1+ cells impairs those behaviors, whereas optogenetic activation induces immediate pup retrieval. In vivo recordings demonstrate preferential activation of MPOAEsr1+ cells during maternal behaviors and changes in MPOA cell responses across reproductive states...
April 4, 2018: Neuron
https://www.readbyqxmd.com/read/29615713/targeted-expression-of-step-function-opsins-in-transgenic-rats-for-optogenetic-studies
#5
Hiroyuki Igarashi, Keiko Ikeda, Hiroshi Onimaru, Ryosuke Kaneko, Kyo Koizumi, Kaoru Beppu, Kayo Nishizawa, Yukari Takahashi, Fusao Kato, Ko Matsui, Kazuto Kobayashi, Yuchio Yanagawa, Shin-Ichi Muramatsu, Toru Ishizuka, Hiromu Yawo
Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29614674/optical-depolarization-of-dcx-expressing-cells-promoted-cognitive-recovery-and-maturation-of-newborn-neurons-via-the-wnt-%C3%AE-catenin-pathway
#6
Ming-Liang Zhao, Shi-Jin Chen, Xiao-Hong Li, Li-Na Wang, Feng Chen, Shi-Jiang Zhong, Cheng Yang, Sheng-Kai Sun, Jian-Jun Li, Hua-Jiang Dong, Yue-Qing Dong, Yi Wang, Chong Chen
Electrical excitability by membrane depolarization is crucial for survival and maturation of newborn cells in the dentate gyrus of the hippocampus. However, traditional technology for membrane depolarization lacks temporal and spatial precision. Optogenetics can be used to activate channelrhodopsin-2 (ChR2), allowing cationic current to depolarize genetically targeted cells. In this study, we used ChR2-EGFP driven by doublecortin (DCX) to promote survival and maturation of newborn cells in the dentate gyrus after traumatic brain injury (TBI)...
March 28, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29596518/all-optical-recording-and-stimulation-of-retinal-neurons-in-vivo-in-retinal-degeneration-mice
#7
Soon Keen Cheong, Jennifer M Strazzeri, David R Williams, William H Merigan
Here we demonstrate the application of a method that could accelerate the development of novel therapies by allowing direct and repeatable visualization of cellular function in the living eye, to study loss of vision in animal models of retinal disease, as well as evaluate the time course of retinal function following therapeutic intervention. We use high-resolution adaptive optics scanning light ophthalmoscopy to image fluorescence from the calcium sensor GCaMP6s. In mice with photoreceptor degeneration (rd10), we measured restored visual responses in ganglion cell layer neurons expressing the red-shifted channelrhodopsin ChrimsonR over a six-week period following significant loss of visual responses...
2018: PloS One
https://www.readbyqxmd.com/read/29580953/effects-of-drugs-of-abuse-on-channelrhodopsin-2-kinetics
#8
Dominic Gioia, Minfu Xu, Wesley Wayman, John Woodward
Channelrhodopsins are light activated ion channels used extensively over the past decade to probe the function of genetically defined neuronal populations and distinct neural circuits with high temporal and spatial precision. The widely used Channelrhodopsin-2 variant (ChR2) is an excitatory opsin that undergoes conformational changes in response to blue light, allowing non-selective passage of protons and cations across the plasma membrane thus leading to depolarization. In the addiction neuroscience field, opsins such as ChR2 provide a means to disambiguate the overlapping circuitry involved in mediating the reinforcing and aversive effects of drugs of abuse as well as to determine the plasticity that can occur in these circuits during the development of dependence...
March 23, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29577530/induction-of-signal-transduction-using-non-channelrhodopsin-type-optogenetic-tools
#9
Yoshibumi Ueda, Moritoshi Sato
Signal transductions are the basis for all cellular functions. Previous studies investigating signal transductions mainly relied on pharmacological inhibition, RNA interference, and constitutive active/dominant negative protein expression systems. However, such studies do not allow the modulation of protein activity in cells, tissues, and organs in animals with high spatial and temporal precision. Recently, non-channelrhodopsin-type optogenetic tools for regulating signal transduction have emerged. These photoswitches address several disadvantages of previous techniques, and allow us to control a variety of signal transductions such as cell membrane dynamics, calcium signaling, lipid signaling, and apoptosis...
March 25, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29577367/bioluminescence-driven-optogenetic-activation-of-transplanted-neural-precursor-cells-improves-motor-deficits-in-a-parkinson-s-disease-mouse-model
#10
Jessica R Zenchak, Brandon Palmateer, Nicolai Dorka, Tariq M Brown, Lina-Marie Wagner, William E Medendorp, Eric D Petersen, Mansi Prakash, Ute Hochgeschwender
The need to develop efficient therapies for neurodegenerative diseases is urgent, especially given the increasing percentages of the population living longer, with increasing chances of being afflicted with conditions like Parkinson's disease (PD). A promising curative approach toward PD and other neurodegenerative diseases is the transplantation of stem cells to halt and potentially reverse neuronal degeneration. However, stem cell therapy does not consistently lead to improvement for patients. Using remote stimulation to optogenetically activate transplanted cells, we attempted to improve behavioral outcomes of stem cell transplantation...
March 25, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29555736/retinal-isomerization-and-water-pore-formation-in-channelrhodopsin-2
#11
Albert Ardevol, Gerhard Hummer
Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel widely used in optogenetics. Photoactivation triggers a trans -to- cis isomerization of a covalently bound retinal. Ensuing conformational changes open a cation-selective channel. We explore the structural dynamics in the early photocycle leading to channel opening by classical (MM) and quantum mechanical (QM) molecular simulations. With QM/MM simulations, we generated a protein-adapted force field for the retinal chromophore, which we validated against absorption spectra...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29540835/author-correction-anion-conducting-channelrhodopsins-with-tuned-spectra-and-modified-kinetics-engineered-for-optogenetic-manipulation-of-behavior
#12
Jonas Wietek, Silvia Rodriguez-Rozada, Janine Tutas, Federico Tenedini, Christiane Grimm, Thomas G Oertner, Peter Soba, Peter Hegemann, J Simon Wiegert
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29531964/overexpression-of-channelrhodopsin-2-interferes-with-the-gabab-receptor-mediated-depression-of-gaba-release-from-the-somatostatin-containing-interneurons-of-the-prefrontal-cortex
#13
Lei Liu, Wataru Ito, Alexei Morozov
Region and cell-type restricted expression of light-activated ion channels is the indispensable tool to study properties of synapses in specific circuits and to monitor synaptic alterations by various stimuli including neuromodulators and behaviors, both ex vivo and in vivo . These analyses require the light-activated proteins or viral vectors for their delivery that do not interfere with the phenomenon under study. Here, we report a case of such interference in which the high-level expression of channelrhodopsin-2 introduced in the somatostatin-positive GABAergic neurons of the dorsomedial prefrontal cortex by an adeno-associated virus vector weakens the presynaptic GABAb receptor-mediated suppression of GABA release...
April 2018: Neurophotonics
https://www.readbyqxmd.com/read/29524231/dynamics-of-neuro-effector-coupling-at-cardiac-sympathetic-synapses
#14
Valentina Prando, Francesca Da Broi, Mauro Franzoso, Anna Pia Plazzo, Nicola Pianca, Maura Francolini, Cristina Basso, Matthew W Kay, Tania Zaglia, Marco Mongillo
AIM: Cardiac sympathetic neurons (SNs) finely tune the rate and strength of heart contractions to match the blood demand, both at rest and during acute stresses, through the release of norepinephrine (NE). Junctional sites at the interface between the two cell types have been observed, but whether direct neuro-cardiac coupling has a role in heart physiology has not thus far been clearly demonstrated. METHODS AND RESULTS: We investigated the dynamics of SN/cardiomyocyte intercellular signalling, both by FRET-based imaging of cAMP in co-cultures, as a readout of cardiac β-AR activation, and in vivo, using optogenetics in transgenic mice with SN-specific expression of Channelrhodopsin-2...
March 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29513711/a-novel-carbon-tipped-single-micro-optrode-for-combined-optogenetics-and-electrophysiology
#15
Dénes Budai, Attila D Vizvári, Zsolt K Bali, Balázs Márki, Lili V Nagy, Zoltán Kónya, Dániel Madarász, Nóra Henn-Mike, Csaba Varga, István Hernádi
Optical microelectrodes (optrodes) are used in neuroscience to transmit light into the brain of a genetically modified animal to evoke and record electrical activity from light-sensitive neurons. Our novel micro-optrode solution integrates a light-transmitting 125 micrometer optical fiber and a 9 micrometer carbon monofilament to form an electrical lead element, which is contained in a borosilicate glass sheathing coaxial arrangement ending with a micrometer-sized carbon tip. This novel unit design is stiff and slender enough to be used for targeting deep brain areas, and may cause less tissue damage compared with previous models...
2018: PloS One
https://www.readbyqxmd.com/read/29512463/application-of-optogenetics-in-gene-therapy
#16
Toshihiro Kushibiki, Miya Ishihara
The optogenetics approach uses a combination of genetic and optical methods to initiate and control functions in specific cells of biological tissues. Since the high-speed control of neuronal activity by irradiating channelrhodopsin-2 with blue light was reported in 2005, tremendous advancement and application of optogenetics in the field of neuroscience, such as in studies that associate neuronal activity with behaviors, have been initiated. Optogenetics is not only used as a research tool, but is also started to apply in the diagnosis of a disease or as therapy in various studies...
March 2, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29486056/defining-the-ionic-mechanisms-of-optogenetic-control-of-vascular-tone-by-channelrhodopsin-2
#17
Nils J G Rorsman, Chau M Ta, Hannah Garnett, Pawel Swietach, Paolo Tammaro
BACKGROUND AND PURPOSE: Optogenetic control of electromechanical coupling in vascular smooth muscle cells (VSMCs) is emerging as a powerful research tool with potential applications in drug discovery and therapeutics. However, the precise ionic mechanisms involved in this control remain unclear. EXPERIMENTAL APPROACH: Cell imaging, patch-clamp electrophysiology, and muscle tension recordings were used to define these mechanisms over a wide range of light stimulations...
February 27, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29483864/differential-regulation-of-bladder-pain-and-voiding-function-by-sensory-afferent-populations-revealed-by-selective-optogenetic-activation
#18
Jennifer J DeBerry, Vijay K Samineni, Bryan A Copits, Christopher J Sullivan, Sherri K Vogt, Kathryn M Albers, Brian M Davis, Robert W Gereau Iv
Bladder-innervating primary sensory neurons mediate reflex-driven bladder function under normal conditions, and contribute to debilitating bladder pain and/or overactivity in pathological states. The goal of this study was to examine the respective roles of defined subtypes of afferent neurons in bladder sensation and function in vivo via direct optogenetic activation. To accomplish this goal, we generated transgenic lines that express a Channelrhodopsin-2-eYFP fusion protein (ChR2-eYFP) in two distinct populations of sensory neurons: TRPV1-lineage neurons ( Trpv1 Cre ;Ai32, the majority of nociceptors) and Nav 1...
2018: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29468190/optogenetic-activation-of-non-nociceptive-a%C3%AE-fibers-induces-neuropathic-pain-like-sensory-and-emotional-behaviors-after-nerve-injury-in-rats
#19
Ryoichi Tashima, Keisuke Koga, Misuzu Sekine, Kensho Kanehisa, Yuta Kohro, Keiko Tominaga, Katsuyuki Matsushita, Hidetoshi Tozaki-Saitoh, Yugo Fukazawa, Kazuhide Inoue, Hiromu Yawo, Hidemasa Furue, Makoto Tsuda
Neuropathic pain is caused by peripheral nerve injury (PNI). One hallmark symptom is allodynia (pain caused by normally innocuous stimuli), but its mechanistic underpinning remains elusive. Notably, whether selective stimulation of non-nociceptive primary afferent Aβ fibers indeed evokes neuropathic pain-like sensory and emotional behaviors after PNI is unknown, because of the lack of tools to manipulate Aβ fiber function in awake, freely moving animals. In this study, we used a transgenic rat line that enables stimulation of non-nociceptive Aβ fibers by a light-activated channel (channelrhodopsin-2; ChR2)...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29462275/excitation-of-cortical-nnos-nk1r-neurons-by-hypocretin-1-is-independent-of-sleep-homeostasis
#20
Rhîannan H Williams, Sarah W Black, Alexia M Thomas, Juliette Piquet, Bruno Cauli, Thomas S Kilduff
We have proposed that cortical nNOS/NK1R interneurons have a role in sleep homeostasis. The hypocretins (orexins) are wake-promoting neuropeptides and hypocretin/orexin (Hcrt) neurons project to the cortex. Hcrt peptides affect deep layer cortical neurons, and Hcrt receptor 1 (Hcrtr1; Ox1r) mRNA is expressed in cortical nNOS/NK1R cells. Therefore, we investigated whether Hcrt neuron stimulation affects cingulate cortex nNOS/NK1R neurons. Bath application of HCRT1/orexin-A evoked an inward current and membrane depolarization in most nNOS/NK1R cells which persisted in tetrodotoxin; optogenetic stimulation of Hcrt terminals expressing channelrhodopsin-2 confirmed these results, and pharmacological studies determined that HCRTR1 mediated these responses...
February 16, 2018: Cerebral Cortex
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