DOCSLIB.ORG

Optogenetics: 10 Years After Chr2 in Neurons--Views from the Community

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Optogenetics: 10 Years After Chr2 in Neurons--Views from the Community UC Office of the President Recent Work Title Optogenetics: 10 years after ChR2 in neurons--views from the community. Permalink https://escholarship.org/uc/item/3wf9h6g2 Journal Nature neuroscience, 18(9) ISSN 1097-6256 Authors Adamantidis, Antoine Arber, Silvia Bains, Jaideep S et al. Publication Date 2015-09-01 DOI 10.1038/nn.4106 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Q&A Optogenetics: 10 years after ChR2 in neurons—views from the community Antoine Adamantidis, Silvia Arber, Jaideep S Bains, Ernst Bamberg, Antonello Bonci, György Buzsáki, Jessica A Cardin, Rui M Costa, Yang Dan, Yukiko Goda, Ann M Graybiel, Michael Häusser, Peter Hegemann, John R Huguenard, Thomas R Insel, Patricia H Janak, Daniel Johnston, Sheena A Josselyn, Christof Koch, Anatol C Kreitzer, Christian Lüscher, Robert C Malenka, Gero Miesenböck, Georg Nagel, Botond Roska, Mark J Schnitzer, Krishna V Shenoy, Ivan Soltesz, Scott M Sternson, Richard W Tsien, Roger Y Tsien, Gina G Turrigiano, Kay M Tye & Rachel I Wilson On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique. euroscientists have long dreamed of and applied to a vast array of questions both in technique has had on neuroscience, we were Nthe ability to control neuronal activ- neuroscience and beyond. curious to know how researchers in the field ity with exquisite spatiotemporal precision. In the intervening years, improvements to feel the advances in optogenetic approaches In this issue, we celebrate the tenth anniver- early techniques have provided the community have influenced their work, what they think sary of a paper published in the September with an optogenetics tool box that has opened the future holds in terms of the application 2005 issue of Nature Neuroscience by a team the door to experiments we could have once of these techniques and what they see as the Nature America, Inc. All rights reserved. America, Inc. Nature led by Karl Deisseroth (Nat. Neurosci. 8, only dreamed of. Controlling neuronal activity obstacles we need to overcome to get there. 5 1263–1268 (2005)). In this study, the authors in real time, we now have the ability to deter- Toward this end, we’ve asked a number of expressed a light-sensitive microbial protein, mine causality between activity patterns in spe- scientists to share their thoughts with us in © 201 Channelrhodopsin-2 (ChR2), in neurons and cific neuronal circuits and brain function and this Q&A. Although we weren’t able to ask showed that exposing these neurons to pulses behavior, enabling researchers to definitively test more than a small fraction of the field, their of light could activate them in a temporally pre- long-held views and advance our understanding answers give an exciting view of the power and npg cise and reliable manner. In the decade since of brain function in both health and disease. potential of optogenetic approaches for under- this paper, ‘optogenetic’ approaches have been Anniversaries are often a time to reflect standing, and even potentially repairing, the widely and enthusiastically adopted by the field and, in light of the seminal influence this nervous system. How do you define optogenetics? Ernst Bamberg: Optogenetics is the use of of genetically encoded molecules to excite and genetically encoded light-activated proteins inhibit neurons. I would prefer it to mean any John Huguenard: Sensitizing neurons to light, for manipulation of cells in an almost non- genetically encoded tool to record or perturb then manipulating neural activity in precise invasive way by light. The most prominent electrical activity of neurons and other excit- spatiotemporal patterns to answer questions tool is ChR2, which allows in a cell-specific able cells. But using a broad name to identify regarding neural circuits and behavior. way the activation of electrical excitable cells a fairly specific subset of tasks was a brilliant via the light-dependent depolarization. The stroke, nonetheless. Michael Häusser: There’s a broad definition combination of ChR2 with hyperpolarizing and a narrow definition. The broad defini- light-driven ion pumps such as the Cl- pump Dan Johnston: I suppose that the accurate tion is rooted in etymology: any approach that halorhodopsin (NphR) allows, with high tem- definition would be genetically encoded opti- combines optical interrogation with genetic poral and spatial precision, the activation or cal sensors, but it is most commonly thought of targeting qualifies as ‘optogenetic’, and that inactivation of neural cells in culture, tissue as genetically encoded light-activated channels. includes the use of genetically encoded activ- and living animals. It’s worth noting, however, and I wasn’t aware of ity sensors. However, most people generally it at the time I reviewed the Boyden paper, but use the term optogenetics to mean the use of Richard Tsien: This 10-year celebration, well- there were two papers that predated this one probes to manipulate activity, and (as is usual deserved by the authors and journal alike, that reported a genetically encoded light-acti- in English) usage normally wins. implicitly points to a narrower definition: use vated channel: Zemelman, B.V. et al. Neuron 33, 1202 VOLUME 18 | NUMBER 9 | SEPTEMBER 2015 NATURE NEUROSCIENCE Q&A 15–22 (2002) and Zemelman, B.V. et al. Proc. would really work in the manners that were clear that the technique was very robust and rep- Natl. Acad. Sci. USA 100, 1352–1357 (2003). promised. I thought it might have some finite licable. Shortly thereafter I decided to do a post- uses, but did not imagine it would be as “revo- doc focusing on this approach, and that’s how I Mark Schnitzer: lutionary” as it turned out to be. ended up at Stanford with Karl Deisseroth. The term ‘optoge- netics’ first appeared Krishna Shenoy: I Antoine Adamantidis: At that time, I was in 2006 in a short had the great pleasure finishing my PhD at the University of Liege, review article pub- of being right here at Belgium, and we were investigating the role lished in Journal Stanford and know- of a unique popula- of Neuroscience to ing Ed and Karl for tion of neurons in the Mark Schnitzer accompany a Society years, so yes, when lateral hypothalamus for Neuroscience their results came in (that is, melanin- mini-symposium that Karl Deisseroth and I and the paper came Krishna Shenoy concentrating hor- had organized. (Deisseroth, K. et al. J. Neurosci. out it was clear it mone) in controlling 26, 10380–10386 (2006)). We considered differ- would be an enormous advance. Could I have ‘dream sleep’. In mam- ent options, such as ‘photogenetics’, but even- predicted how revolutionary it would be? mals, this deep sleep Antoine Adamantidis tually settled on optogenetics as the best term No, there I’m afraid I would have underesti- stage lasts classically to describe techniques that combined optical mated the full extent to which it has been a few minutes, which made it difficult to study and genetic facets. Notably, our original intent neuroscience-wide seismic shift! with conventional ‘low temporal’ approaches was to cover both genetically targeted optical (pharmacology, KO, KI, etc.) without altering control and imaging under a single umbrella Sheena Josselyn: I thought the data were other sleep stages. Thus, when the Boyden/ term. Nevertheless, I have subsequently always interesting, but likely not replicable and defi- Deisseroth publication came out, I thought, preferred a narrower interpretation of optoge- nitely not generalizable. I thought optogenet- “This is it! That’s what we need!” Since I was netics that covers only the control approaches ics would not work reliably and, even if it did, joining the laboratory of Professor Luis de and the wonderful field that grew out of Karl’s the technique would be so complicated as to Lecea at Stanford University a few months later, seminal 2005 paper in Nature Neuroscience; be out of reach for most neuroscience labs. My I emailed Karl about this idea, who replied, “OK, the broader interpretation of optogenetics that initial impression was that optogenetics would let’s meet when you get here!” We did meet, includes imaging is so general that, in some be highly parameter-sensitive and would take and, together with Dr. Feng Zhang, brought it respects, it can be vague. My impression is that lots of fiddling to get any kind of effect. I was to brain slices and freely moving mice to publish a substantial majority of the usages of the term definitely in the camp that didn’t think it would the first in vivo optogenetic paper establishing optogenetics in the neuroscience literature fol- have an impact on my kind of neuroscience. a causal role between hypocretin/orexin cells lows the narrower interpretation. and arousal (Adamantidis, A. et al., Nature 450, Scott Sternson: I thought that if it worked as 420–424 (2007)). Thus, yes, I believe this was a Rachel Wilson: I think of optogenetic tools as Nature America, Inc. All rights reserved. America, Inc. Nature advertised, then it would be exactly the tool transformative technology since early on! 5 a set of wrenches in a larger toolkit of geneti- that I’d been looking for since I started in neu- cally encoded effec- roscience. Thomas Insel: While everyone assumes opto- © 201 tors. This includes genetics is a great technology, reviewers on NIH effectors activated Gina Turrigiano: Intense excitement. I study sections in 2005 by heat, as well as thought the work leading up to this study was did not embrace this npg effectors activated by a beautiful example of basic curiosity-driven idea.
Load more

Recommended publications
  • Friday, October 27, 2017 Kaufman Music Center
    2017 INTERNATIONAL MENTAL HEALTH RESEARCH SYMPOSIUM Friday, October 27, 2017 9:00am–4:30pm Kaufman Music Center 129 West 67th Street New York, NY 10023 Welcome Welcome to our International Mental Health Nationally recognized for broad expertise in Research Symposium. Today we will hear from education, research, clinical care and health the Foundation’s 2017 Outstanding Achieve- policy, today he will offer his thoughts on break- ment Prizewinners and two exceptional Young through opportunities for mental health. Investigator Grantees, on topics ranging from schizophrenia and addiction to childhood We would like to extend special thanks to our interventions and the brain circuitry behind sponsors The Allergan Foundation and Sunov- mood disorders. ion Pharmaceuticals, Inc. for their charitable support of this year’s symposium. The Outstanding Achievement Prizewin- ners are selected by special committees of We hope today’s conference will inspire you. the Foundation’s Scientific Council, a volun- Our shared commitment to advance science teer group of 177 pre-eminent mental health will change what it means to live with a mental professionals across disciplines in brain and illness and open possibilities for more people to behavior research, who also select each year’s live full, happy, and productive lives. In our 30th Young Investigator, Independent Investiga- anniversary year, I thank you for your ongo- tor and Distinguished Investigator Grant- ing support to help us get closer to realizing ees. Since 1987, the Foundation has awarded this vision. $380 million to fund more than 5,500 grants to more than 4,500 scientists around the Sincerely, world. These awards are made specifically to fill a gap in funding innovative research that may not be supported elsewhere, but is vital for advancement in the fields of neuroscience and psychiatry.
    [Show full text]
  • 2018 Rapport Annuel
    Rapport annuel 2018 Mai 2019 - TABLE DES MATIÈRES À propos de Gairdner 2 Message du président du conseil 3 Message de la présidente et directrice scientifique 4 Revue de l’année 2018 5 Lauréats des prix Canada Gairdner 2018 7 Programme de sensibilisation des étudiants 2018 9 Programme national 2018 13 Conférence des lauréats des Prix Gairdner 2018 16 Symposium de recherche Canada Gairdner 2018 17 Autres programmes de Gairdner à travers le Canada 18 Gairdner remercie ses bailleurs de fonds de 2018 23 L’année à venir : objectifs pour 2019 24 Gouvernance 25 Conseil d’administration 2018 25 Comités permanents du conseil d’administration 26 Comités de la Fondation Gairdner 27 Comité d’examen médical 27 Conseil consultatif médical 28 Comité consultatif du Prix Wightman 30 Comité consultatif du Prix en santé mondiale 30 Faits saillants financiers de 2018 31 Personnel de la Fondation Gairdner 32 Rapport d’audit 33 Fondation Gairdner – Rapport annuel 2018 1 À PROPOS DE GAIRDNER Historique La Fondation Gairdner a été créée en 1957 dans le but de décerner des prix annuels à des chercheurs individuels dont les découvertes en sciences biomédicales ont eu un impact majeur sur le progrès de la science et sur la santé humaine. Chaque année, sept prix sont décernés : cinq Prix internationaux Canada Gairdner, pour l’excellence en recherche biomédicale, le Prix Canada Gairdner en santé mondiale John Dirks, pour des réalisations exceptionnelles en recherche sur la santé mondiale, et le Prix Canada Gairdner Wightman, réservé à un scientifique canadien ayant démontré un leadership exceptionnel en sciences médicales au Canada.
    [Show full text]
  • From Channelrhodopsins to Optogenetics ACCESS
    Perspective OPEN From channelrhodopsins to optogenetics ACCESS From channelrhodopsins to optogenetics We did not expect that research on the and identified the role of Ca2þ influx in forming a single protein complex (Braun molecular mechanism of algal phototaxis flagellar beat frequency changes (Halldal, & Hegemann, 1999). or archaeal light-driven ion transport 1957, Schmidt & Eckert, 1976). Then Oleg In parallel, biophysicists had character- might interest readers of a medical Sineshchekov from Moscow State Uni- ized the precise nature of light-regulated journal when we conceived and per- versity recorded electrical light responses ion transport across cellular membranes. formed our experiments a decade ago. On from Haematococcus pluvialis, an alga Some of these studies started with the other hand, it did not escape our known for the production of the anti- investigations on animal rhodopsin and attention that channelrhodopsin is helping oxidant Astaxanthine (Litvin et al, 1978). even suggested rhodopsin-mediated an ever-increasing number of researchers Oleg used a suction pipette technique light-induced calcium entry with rhodop- to address their specific questions. For applied at the time by Dennis Baylor for sin itself as the carrier for calcium (Cone, example, the channelrhodopsin approach recording photocurrents from bovine 1972). Several decades later, we know is used to study the molecular events photoreceptor rods and cones. But Oleg’s that animal-type rhodopsins are G pro- during the induction of synaptic plasticity publication gave no hints about the type tein-coupled receptors indirectly modu- or to map long-range connections from of photoreceptor involved. Kenneth W. lating ion channel activity via signalling one side of the brain to the other, and to Foster however, a physicist at Mount molecules.
    [Show full text]
  • Optogenetics: Using Light to Control the Brain by Edward S. Boyden, Ph.D
    Optogenetics: Using Light to Control the Brain By Edward S. Boyden, Ph.D. Courtesy of the MIT McGovern Institute, Julie Pryor, Charles Jennings, Sputnik Animation, and Ed Boyden. Editor’s note: The brain is densely packed with interconnected neurons, but until about six years ago, it was difficult for researchers to isolate neurons and neuron types to determine their individual roles in brain processes. In 2004 however, scientists, including author Edward S. Boyden, Ph.D., found that the neural expression of a protein, channelrhodopsin-2 (ChR2), allowed light to activate or silence brain cells. This technology, now known as optogenetics, is helping scientists determine the functions of specific neurons in the brain, and could play a significant role in treating medical issues as diverse as sleep disorders and vision impairment. Article available online at http://dana.org/news/cerebrum/detail.aspx?id=34614 1 The brain is an incredibly densely wired computational circuit, made out of an enormous number of interconnected cells called neurons, which compute using electrical signals. These neurons are heterogeneous, falling into many different classes that vary in their shapes, molecular compositions, wiring patterns, and the ways in which they change in disease states. It is difficult to analyze how these different classes of neurons work together in the intact brain to mediate the complex computations that support sensations, emotions, decisions, and movements—and how flaws in specific neuron classes result in brain disorders. Ideally, one would study the brain using a technology that would enable the control of the electrical activity of just one type of neuron, embedded within a neural circuit, in order to determine the role that that type of neuron plays in the computations and functions of the brain.
    [Show full text]
  • On the Technology Prospects and Investment Opportunities for Scalable Neuroscience
    On the Technology Prospects and Investment Opportunities for Scalable Neuroscience Thomas Dean1,2,3 Biafra Ahanonu3 Mainak Chowdhury3 Anjali Datta3 Andre Esteva3 Daniel Eth3 Nobie Redmon3 Oleg Rumyantsev3 Ysis Tarter3 1 Google Research, 2 Brown University, 3 Stanford University Contents 1 Executive Summary 1 2 Introduction 4 3 Evolving Imaging Technologies 6 4 Macroscale Reporting Devices 10 5 Automating Systems Neuroscience 14 6 Synthetic Neurobiology 16 7 Nanotechnology 20 8 Acknowledgements 28 A Leveraging Sequencing for Recording — Biafra Ahanonu 28 B Scalable Analytics and Data Mining — Mainak Chowdhury 32 C Macroscale Imaging Technologies — Anjali Datta 35 D Nanoscale Recording and Wireless Readout — Andre Esteva 38 E Hybrid Biological and Nanotechnology Solutions — Daniel Eth 41 F Advances in Contrast Agents and Tissue Preparation — Nobie Redmon 44 G Microendoscopy and Optically Coupled Implants — Oleg Rumyantsev 46 H Opportunities for Automating Laboratory Procedures — Ysis Tarter 49 i 1 Executive Summary Two major initiatives to accelerate research in the brain sciences have focused attention on devel- oping a new generation of scientific instruments for neuroscience. These instruments will be used to record static (structural) and dynamic (behavioral) information at unprecedented spatial and temporal resolution and report out that information in a form suitable for computational analysis. We distinguish between recording — taking measurements of individual cells and the extracellu- lar matrix — and reporting — transcoding, packaging and transmitting the resulting information for subsequent analysis — as these represent very different challenges as we scale the relevant technologies to support simultaneously tracking the many neurons that comprise neural circuits of interest. We investigate a diverse set of technologies with the purpose of anticipating their devel- opment over the span of the next 10 years and categorizing their impact in terms of short-term [1-2 years], medium-term [2-5 years] and longer-term [5-10 years] deliverables.
    [Show full text]
  • Optogenetic Replacement of Odor Stimuli in Drosophila Group Conditioning Experiments
    Optogenetic replacement of Odor stimuli in Drosophila group conditioning experiments Max Planck Institute for Neurobiologie and Ludwig-Maximilians-Universit¨at Munchen¨ Master Thesis for physics by Marc Eppler 6th of December 2016 2 Optogenetic als Ersatz fur¨ Duft bei langzeit-stimulations-konditionierungs- Experimente in Drosophila Max Planck Institute fur¨ Neurobiologie and Ludwig-Maximilians-Universit¨at Munchen¨ Master Arbeit fur¨ Physik von Marc Eppler 6ter Dezember 2016 2 Optogenetic replacement of Odor stimuli in Drosophila group conditioning experiments Developed in the Lab of and supervised by Dr. Ilona Grunwald-Kadow Chemosensory coding and decision-making Marc Christian Eppler Bietigheim-Bissingen 7. November 1988 Handed over at the 6th of December by Marc Eppler Corrector: Prof. Dr. Wilfried Denk 3 Abstract Optogenetics is one of the most powerful recenty discovered tools for the field of Neuroscience and does represent very well the interdisciplinary way modern research is more and more conducted. While replacing traditional way of doing experiments and bringing further possibilities to it, there are also difficulties occurring by the artificial nature of inducing signals into a living model organism. Specially when trying to reconstruct behavior to explore the underlining complexity of the brain it is not trivial to get the the complex circuits within the brain to recognize the stimulus in a way that makes contextual sense and then perform tasks like learning and forming conditioned memories. This work explores a way to have groups of the model organism Drosophila melanogaster being conditioned by imitating an odor stimulus with optogenetics over longer periods of time, which always has been a problem with real odor due to its invisible and hard to control dynamic nature.
    [Show full text]
  • Long-Lasting Potentiation of Gabaergic Synapses in Dopamine Neurons After a Single in Vivo Ethanol Exposure
    The Journal of Neuroscience, March 15, 2002, 22(6):2074–2082 Long-Lasting Potentiation of GABAergic Synapses in Dopamine Neurons after a Single In Vivo Ethanol Exposure Miriam Melis, Rosana Camarini, Mark A. Ungless, and Antonello Bonci Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, California 94110 The mesolimbic dopamine (DA) system originating in the ventral (diethoxymethyl) phosphinic acid shifted PPD to PPF, indicating tegmental area (VTA) is involved in many drug-related behav- that presynaptic GABAB receptor activation, likely attributable iors, including ethanol self-administration. In particular, VTA to GABA spillover, might play a role in mediating PPD in the activity regulating ethanol consummatory behavior appears to ethanol-treated mice. The activation of adenylyl cyclase by be modulated through GABAA receptors. Previous exposure to forskolin increased the amplitude of GABAA IPSCs and the ethanol enhances ethanol self-administration, but the mecha- frequency of mIPSCs in the saline- but not in the ethanol- nisms underlying this phenomenon are not well understood. In treated animals. Conversely, the protein kinase A (PKA) inhibitor this study, we examined changes occurring at GABA synapses N-[z-( p-bromocinnamylamino)ethyl]-5-isoquinolinesulfona- onto VTA DA neurons after a single in vivo exposure to ethanol. mide significantly decreased both the frequency of spontane- We observed that evoked GABAA IPSCs in DA neurons of ous mIPSCs and the amplitude of GABAA IPSCs in the ethanol- ethanol-treated animals exhibited paired-pulse depression treated mice but not in the saline controls. The present results (PPD) compared with saline-treated animals, which exhibited indicate that potentiation of GABAergic synapses, via a PKA- paired-pulse facilitation (PPF).
    [Show full text]
  • Report Drugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Neuron, Vol. 37, 577–582, February 20, 2003, Copyright 2003 by Cell Press Drugs of Abuse and Stress Trigger Report a Common Synaptic Adaptation in Dopamine Neurons Daniel Saal,1,3 Yan Dong,1,3 Antonello Bonci,2 is the subject of debate (Berridge and Robinson, 1998), and Robert C. Malenka1,* there is no doubt that the discovery of this common 1Nancy Pritzker Laboratory action of addictive drugs, despite their very different Department of Psychiatry and Behavioral Sciences molecular actions, has had a major influence on thinking Stanford University School of Medicine about both the neurobiological basis of addiction as Palo Alto, California 94304 well as the brain mechanisms mediating reinforcement 2 Ernest Gallo Clinic and Research Center and reward-based learning (Waelti et al., 2001). Department of Neurology and Recently we found that a single in vivo exposure to Wheeler Center for the Neurobiology of Addiction cocaine caused an enhancement of synaptic strength University of California, San Francisco at excitatory synapses on midbrain DA neurons (Ungless San Francisco, California 94110 et al., 2001) and that this shared several features with long-term potentiation (LTP), the leading model for the cellular changes that mediate learning and memory Summary (Martin et al., 2000). Here we examine whether in vivo administration of other commonly abused drugs causes Drug seeking and drug self-administration in both ani- a similar synaptic change. Furthermore, because in both mals and humans can be triggered by drugs of abuse humans and animals stress facilitates the initial acquisi- themselves or by stressful events.
    [Show full text]
  • BIOGRAPHICAL SKETCH NAME: Antonello Bonci Era COMMONS
    OMB No. 0925-0001/0002 (Rev. 10/15 Approved Through 10/31/2018) BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Antonello Bonci eRA COMMONS USER NAME (credential, e.g., agency login): ANTONB POSITION TITLE: Scientific Director EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) DEGREE Completion (if Date FIELD OF STUDY INSTITUTION AND LOCATION applicable) MM/YYYY Vollum Institute for Advanced Biomedical Research, Postdoctoral 1994-1996 Biomedical Research Portland, OR, USA Fellowship School of Neurology, University of Rome “Tor Resident 1991-1995 Neurology Vergata”, Rome, Italy Catholic University of Sacred Heart, School of M.D. 1985-1991 Medicine Medicine, Rome, Italy A. Personal Statement I joined the National Institutes of Health (NIH) in 2010 as Scientific Director of the National Institute on Drug Abuse (NIDA). I was professor in residence in the Department of Neurology at the University of California, San Francisco (UCSF) and held the Howard J. Weinberg Endowed Chair in Addiction Research; as well as Associate Director for Extramural Affairs at the Ernest Gallo Clinic and Research Center. My laboratory was the first to demonstrate that drugs of abuse such as cocaine produce long-lasting modifications on the strength of the connections between neurons. This form of cellular memory is called long-term potentiation (LTP.) This finding cast a new light on the phenomenon of drug addiction, which could now be seen as a process of maladaptive learning and memory at the cellular level.
    [Show full text]
  • Globus Pallidus Dynamics Reveal Covert Strategies for Behavioral Inhibition
    This is a repository copy of Globus pallidus dynamics reveal covert strategies for behavioral inhibition. White Rose Research Online URL for this paper: http://eprints.whiterose.ac.uk/161807/ Version: Accepted Version Article: Gu, B.-M., Schmidt, R. orcid.org/0000-0002-2474-3744 and Berke, J.D. (2020) Globus pallidus dynamics reveal covert strategies for behavioral inhibition. eLife. e57215. https://doi.org/10.7554/eLife.57215 © 2020 The Authors. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) permitting unrestricted use and redistribution provided that the original author and source are credited. Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing [email protected] including the URL of the record and the reason for the withdrawal request. [email protected] https://eprints.whiterose.ac.uk/ ! 1 Globus pallidus dynamics reveal covert strategies for behavioral inhibition. 2 Bon-Mi Gu1, Robert Schmidt2, and Joshua D. Berke1,3* 3 1) Department of Neurology, University of California, San Francisco, USA. 4 2) Department of Psychology, University of Sheffield, UK. 5 3) Department of Psychiatry; Neuroscience Graduate Program; Kavli Institute for Fundamental Neuroscience; 6 Weill Institute for Neurosciences, University of California, San Francisco, USA.
    [Show full text]
  • Coherent Control of Optogenetic Switching by Stimulated Depletion
    Coherent Control of Optogenetic Switching by Stimulated Depletion Quenching Zachary Quine1, Alexei Goun1, Karl Gerhardt, 2, Jeffrey Tabor2, Herschel Rabitz1 1Department of Chemistry, Princeton University 2Department of Bioengineering, Rice University October 29, 2018 Abstract Optogenetics is a revolutionary new field of biotechnology, achieving optical control over biological functions in living cells by genetically inserting light sensitive proteins into cellular signaling pathways. Applications of optogenetic switches are expanding rapidly, but the technique is hampered by spectral cross-talk: the broad absorption spectra of compatible biochemical chromophores limits the number of switches that can be independently controlled and restricts the dynamic range of each switch. In the present work we develop and implement a non-linear optical photoswitching capability, Stimulated Depletion Quenching (SDQ), is used to overcome spectral cross-talk by exploiting the molecules' unique dynamic response to ultrashort laser pulses. SDQ is employed to enhance the control of Cph8, a photo- reversible phytochrome based optogenetic switch designed to control gene expression in E. Coli bacteria. The Cph8 switch can not be fully converted to it's biologically inactive state (PFR) by linear photos- witching, as spectral cross-talk causes a reverse photoswitching reaction to revert to it back to the active state (PR). SDQ selectively halts this reverse reaction while allowing the forward reaction to proceed. arXiv:1810.11432v1 [q-bio.QM] 26 Oct 2018 The
    [Show full text]
  • A Subpopulation of Neurochemically-Identified Ventral Tegmental Area Dopamine Neurons Is Excited by Intravenous Cocaine
    The Journal of Neuroscience, February 4, 2015 • 35(5):1965–1978 • 1965 Systems/Circuits A Subpopulation of Neurochemically-Identified Ventral Tegmental Area Dopamine Neurons Is Excited by Intravenous Cocaine X Carlos A. Mejias-Aponte,1 Changquan Ye,1 Antonello Bonci,2,4 Eugene A. Kiyatkin,3 and Marisela Morales1 1Integrative Neuroscience Research Branch, Neuronal Networks Section, 2Cellular Neurobiology Research Branch, Synaptic Physiology Section, and 3Behavioral Neuroscience Research Branch, Behavioral Neuroscience Section, In Vivo Electrophysiology Unit, Intramural Research Program, National Institute of Drug Abuse, Baltimore, Maryland 21224, and 4Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in re- sponse to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes inburstfiring.InhibitedneuronsweremoreabundantintheposteriorVTA,whereasexcitedneuronsweredistributedevenlythroughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited.
    [Show full text]