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Neuregulin Induces the Expression of Transcription Factors and Myosin Heavy Chains Typical of Muscle Spindles in Cultured Human Muscle
Neuregulin induces the expression of transcription factors and myosin heavy chains typical of muscle spindles in cultured human muscle Christian Jacobson*, David Duggan†, and Gerald Fischbach‡§ *Microarray Unit, Genetics and Genomics Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892; †Translational Genomics Research Institute (TGen), Phoenix, AZ 85004; and ‡Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032 Contributed by Gerald Fischbach, June 29, 2004 Neuregulin (NRG) (also known as ARIA, GGF, and other names) is (DRG) (28), proprioceptive sensory neurons in particular, ex- a heparin sulfate proteoglycan secreted into the neuromuscular press NRG early in development (14, 29, 30). While these junction by innervating motor and sensory neurons. An integral experiments were ongoing, reports appeared implicating NRG in part of synapse formation, we have analyzed NRG-induced the development of muscle spindles. Hippenmeyer et al. (14) changes in gene expression over 48 h in primary human myotubes. showed that NRG induces the expression of early growth We show that in addition to increasing the expression of acetyl- response 3 (Egr3), a transcription factor that is critical to the choline receptors on the myotube surface, NRG treatment results differentiation of muscle spindle fibers (31). Evidence for NRG’s in a transient increase of several members of the early growth role in spindle formation is re-enforced by the phenotypic response (Egr) family of transcription factors. Three Egrs, Egr1, -2, similarities between conditional Erb2 knockout animals and and -3, are induced within the first hour of NRG treatment, with Egr3 null mice (13, 15, 24). -
Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System
International Journal of Molecular Sciences Review Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System Shenglong Zou and Ujendra Kumar * Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z4, Canada; [email protected] * Correspondence: [email protected]; Tel.: +1-604-827-3660; Fax: +1-604-822-3035 Received: 9 February 2018; Accepted: 11 March 2018; Published: 13 March 2018 Abstract: The biological effects of cannabinoids, the major constituents of the ancient medicinal plant Cannabis sativa (marijuana) are mediated by two members of the G-protein coupled receptor family, cannabinoid receptors 1 (CB1R) and 2. The CB1R is the prominent subtype in the central nervous system (CNS) and has drawn great attention as a potential therapeutic avenue in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Furthermore, cannabinoids also modulate signal transduction pathways and exert profound effects at peripheral sites. Although cannabinoids have therapeutic potential, their psychoactive effects have largely limited their use in clinical practice. In this review, we briefly summarized our knowledge of cannabinoids and the endocannabinoid system, focusing on the CB1R and the CNS, with emphasis on recent breakthroughs in the field. We aim to define several potential roles of cannabinoid receptors in the modulation of signaling pathways and in association with several pathophysiological conditions. We believe that the therapeutic significance of cannabinoids is masked by the adverse effects and here alternative strategies are discussed to take therapeutic advantage of cannabinoids. Keywords: cannabinoid; endocannabinoid; receptor; signaling; central nervous system 1. Introduction The plant Cannabis sativa, better known as marijuana, has long been used for medical purpose throughout human history. -
Many Specialists for Suppressing Cortical Excitation Andreas Burkhalter Washington University School of Medicine in St
Washington University School of Medicine Digital Commons@Becker Open Access Publications 12-2008 Many specialists for suppressing cortical excitation Andreas Burkhalter Washington University School of Medicine in St. Louis Follow this and additional works at: https://digitalcommons.wustl.edu/open_access_pubs Part of the Medicine and Health Sciences Commons Recommended Citation Burkhalter, Andreas, ,"Many specialists for suppressing cortical excitation." Frontiers in Neuroscience.,. 1-167. (2008). https://digitalcommons.wustl.edu/open_access_pubs/495 This Open Access Publication is brought to you for free and open access by Digital Commons@Becker. It has been accepted for inclusion in Open Access Publications by an authorized administrator of Digital Commons@Becker. For more information, please contact [email protected]. FOCUSED REVIEW published: 15 December 2008 doi: 10.3389/neuro.01.026.2008 Many specialists for suppressing cortical excitation Andreas Burkhalter* Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO, USA Cortical computations are critically dependent on GABA-releasing neurons for dynamically balancing excitation with inhibition that is proportional to the overall level of activity. Although it is widely accepted that there are multiple types of interneurons, defining their identities based on qualitative descriptions of morphological, molecular and physiological features has failed to produce a universally accepted ‘parts list’, which is needed to understand the roles that interneurons play in cortical processing. A list of features has been published by the Petilla Interneurons Nomenclature Group, which represents an important step toward an unbiased classification of interneurons. To this end some essential features have recently been studied quantitatively and their association was examined using multidimensional cluster analyses. -
Neuroscience in Brief
Neuroscience in Brief On the Move from Academia to Industry: Established Neuroscientists Who Have Made the Transition from Academia to Industry Are Finding Different Rewards in a New Environment Contributed by Laura Bonetta In 1997, neuroscientist Frank Walsh was Wyeth Research in Pennsylvania, as exec- asked by Peter Goodfellow whether he utive vice president for discovery research would be interested in leading the neuro- worldwide. At Wyeth, a company that has science division at SmithKline Beecham several blockbuster drugs in the market, in- Pharmaceuticals (now GlaxoSmithKline) in cluding the antidepressant Effexor XR (ven- Harlow, UK. Goodfellow, a well known ge- lafaxine), drug discovery depended mostly neticist, had joined the company from the University of Cambridge a few years earlier. on a large chemistry effort and on broad in- Although Walsh, then research dean at teractions with colleagues. “As a biologist, it Guy’s Hospital in London, and head of a is typically difficult to gain access to chemis- well-funded research lab, was not looking to try. It is very pleasing to have chemists to move, he started thinking about the oppor- work with on projects,” says Walsh. tunities created by working in an industrial environment. “I was working in a large Looking for change medical school on diseases. But I had a lim- Unlike Walsh, when Richard Scheller left ited ability to impact on human health. That academia, he was actively seeking a is just the nature of how an academic insti- change. He had been a professor at Stan- tution is set up,” he says. In addition, Smith- ford University School of Medicine in Kline was “a very academically oriented “One of the main differences is the availability of resources company. -
GSK3 Signalling Regulates Mammalian Axon Regeneration by Inducing the Expression of Smad1
ARTICLE Received 28 Mar 2013 | Accepted 27 Sep 2013 | Published 28 Oct 2013 DOI: 10.1038/ncomms3690 PI3K–GSK3 signalling regulates mammalian axon regeneration by inducing the expression of Smad1 Saijilafu1,*, Eun-Mi Hur1,2,*, Chang-Mei Liu1, Zhongxian Jiao1, Wen-Lin Xu1 & Feng-Quan Zhou1,3 In contrast to neurons in the central nervous system, mature neurons in the mammalian peripheral nervous system (PNS) can regenerate axons after injury, in part, by enhancing intrinsic growth competence. However, the signalling pathways that enhance the growth potential and induce spontaneous axon regeneration remain poorly understood. Here we reveal that phosphatidylinositol 3-kinase (PI3K) signalling is activated in response to peripheral axotomy and that PI3K pathway is required for sensory axon regeneration. Moreover, we show that glycogen synthase kinase 3 (GSK3), rather than mammalian target of rapamycin, mediates PI3K-dependent augmentation of the growth potential in the PNS. Furthermore, we show that PI3K–GSK3 signal is conveyed by the induction of a transcription factor Smad1 and that acute depletion of Smad1 in adult mice prevents axon regeneration in vivo. Together, these results suggest PI3K–GSK3–Smad1 signalling as a central module for promoting sensory axon regeneration in the mammalian nervous system. 1 Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. 2 Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea. 3 The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. * These authors contributed equally to this work. -
Neural Construction of Conscious Perception
Neural construction of conscious perception Thesis by Janis Karan Hesse In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy CALIFORNIA INSTITUTE OF TECHNOLOGY Pasadena, California 2020 (Defended May 28th, 2020) ii 2020 Janis Hesse ORCID: 0000-0003-0405-8632 iii ACKNOWLEDGEMENTS I'd like to thank Doris Tsao for being an incredible advisor and undepletable source of ideas, advice and inspiration, for sharing her passion for science with me, and giving me the courage to ask big questions. I am very happy about the choice of my thesis committee. Markus Meister, Ueli Rutishauser, and Ralph Adolphs contributed substantially by providing useful ideas, discussions, and criticisms throughout this thesis. I want to thank current and past members of the Tsao lab, including Varun Wadia, Nicole Schweers, Audo Flores, Pinglei Bao, Liang She, Steven Le Chang, Xueqi Cheng Shay Ohayon, Tomo Sato, Joseph Wekselblatt, Francisco Luongo, Lu Liu, Anne Martin, Jessa Alexander, Erin Koch, Jialiang Lu, Yuelin Shi, Alex Farhang, Irene Caprara, Frank Lanfranchi, Lindsay Salay, Hongsun Guo, Abriana Sustaita, and Sebastian Moeller, who have all been very willing to offer me help whenever I needed, taught me the different techniques in the lab, and gave me great comments, ideas and discussions. I would also like to note that the work on human epilepsy patients described in Chapter VI is as much of Varun Wadia's work as it is mine. I am grateful to have started my PhD with such a lovely cohort. My PhD would not have been as fun without Mason McGill, Vineet Augustine, Gabriela Tavares, and Ryan Cho. -
LHX2 Interacts with the Nurd Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11
194 • The Journal of Neuroscience, January 4, 2017 • 37(1):194–203 Development/Plasticity/Repair LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11 X Bhavana Muralidharan,1 Zeba Khatri,1 Upasana Maheshwari,1 Ritika Gupta,1 Basabdatta Roy,1 Saurabh J. Pradhan,2,3 Krishanpal Karmodiya,2 XHari Padmanabhan,1,4,5 XAshwin S. Shetty,1,4 Chinthapalli Balaji,1 X Ullas Kolthur-Seetharam,1 XJeffrey D. Macklis,4,5 Sanjeev Galande,2 and XShubha Tole1 1Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India, 2Indian Institute of Science, Education, and Research, Pune 411008, India, 3Symbiosis School of Biomedical Sciences, Symbiosis International University, Lavale, Pune, 4Department of Stem Cell and Regenerative Biology and 5Center for Brain Science, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138 In the developing cerebral cortex, sequential transcriptional programs take neuroepithelial cells from proliferating progenitors to dif- ferentiated neurons with unique molecular identities. The regulatory changes that occur in the chromatin of the progenitors are not well understood. During deep layer neurogenesis, we show that transcription factor LHX2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. We demonstrate that LHX2 binds to the nucleosome remodeling and histone deacetylase histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. When LHX2 is absent, active histone marks at the Fezf2 and Sox11 loci are increased. Loss of LHX2 produces an increase, and overexpression of LHX2 causes a decrease, in layer 5 Fezf2 and CTIP2-expressing neurons. -
NGF-Dependent Retrograde Signaling: Survival Versus Death
Cell Research (2009) 19:525-526. npg © 2009 IBCB, SIBS, CAS All rights reserved 1001-0602/09 $ 30.00 RESEARCH HIGHLIGHT www.nature.com/cr NGF-dependent retrograde signaling: survival versus death Yang Zhou1, Ting-Jia Lu1, Zhi-Qi Xiong1 1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road Shanghai 200031, China Cell Research (2009) 19:525-526. doi: 10.1038/cr.2009.47; published online 4 May 2009 Nerve growth factor (NGF) was which could also provide as the ret- nisms underlying NGF-dependent first discovered more than 5 decades rograde signals [7]. These hypotheses retrograde signaling. Previous studies ago as a molecule that promotes the are not mutually exclusive, and mul- from Campenot’s laboratory demon- survival and maturation of develop- tiple retrograde signals may exist. strated that NGF applied to distal ax- ing neurons in the peripheral nervous In this issue, Mok and colleagues ons of sympathetic neurons supports system [1]. NGF released from target describe a fundamentally different neuronal survival without transport of cells activates tropomyosin-related retrograde mechanism in which NGF NGF towards the cell bodies or TrkA kinase A (TrkA) on axon terminals and suppresses an apoptotic signal in distal phosphorylation in the cell bodies, triggers activation of PI3K/Akt, MEK/ axons [8]. Campenot’s group devel- suggesting that NGF binding to TrkA ERK, and PLCg signaling pathways. oped compartmentalized cultures of in distal axons triggers its downstream The signal then travels retrogradely sympathetic neurons which could seg- signaling cascades locally; afterwards along axon to cell body to promote regate the distal axons from cell bod- the signals travel retrogradely to the neuronal survival [2]. -
Untangling Schizophrenia the Genetics of Mental Illness
Poetic Voices • Commencement • Liberal-Arts MakeoverMakeover JULY-AUGUST 2017 • $4.95 Untangling Schizophrenia The genetics of mental illness Reprinted from Harvard Magazine. For more information, contact Harvard Magazine, Inc. at 617-495-5746 S:7” S:9.25” MERCK INVENTS TO KEEP JOY ALIVE So today, on Claudia’s wedding day, her grandfather Eduardo is there for the milestone event. Creating another special memory for the both of them. For more than a century, Merck has been inventing medicines and vaccines for many of the world’s most challenging diseases. Today, we’re exploring entirely new approaches in our search to prevent Alzheimer’s. So people remain healthy and present, able to share every precious moment with the ones they love. Learn more at Merck.com/InventingForLife Keep Joy Alive Copyright ©2017 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA. All Rights Reserved. CORP-1210605-0005 06/17 Reprinted from Harvard Magazine. For more information, contact Harvard Magazine, Inc. at 617-495-5746 170701_Merck.indd 1 5/17/17 3:31 PM JULY-AUGUST 2017, VOLUME 119, NUMBER 6 FEATURES 32 Poetry, Voiced | by Sophia Nguyen Preserving the treasures of the Woodberry Poetry Room 38 Vita: Blanche Ames | by Laura J. Snyder Brief life of an intrepid botanical illustrator: 1878-1969 p. 32 40 Probing Psychoses | by Courtney Humphries Genetic and genomic clues to understanding schizophrenia p. 15 47 An Educated Core | by John S. Rosenberg Three bold attempts to redesign the liberal arts JOHN HARVARD’S JOURNAL 14 Abdi, Biden…Zuckerberg: the 366th Commencement, animated, academic—and political. -
Pin Faculty Directory
Harvard University Program in Neuroscience Faculty Directory 2019—2020 April 22, 2020 Disclaimer Please note that in the following descripons of faculty members, only students from the Program in Neuroscience are listed. You cannot assume that if no students are listed, it is a small or inacve lab. Many faculty members are very acve in other programs such as Biological and Biomedical Sciences, Molecular and Cellular Biology, etc. If you find you are interested in the descripon of a lab’s research, you should contact the faculty member (or go to the lab’s website) to find out how big the lab is, how many graduate students are doing there thesis work there, etc. Program in Neuroscience Faculty Albers, Mark (MGH-East)) De Bivort, Benjamin (Harvard/OEB) Kaplan, Joshua (MGH/HMS/Neurobio) Rosenberg, Paul (BCH/Neurology) Andermann, Mark (BIDMC) Dettmer, Ulf (BWH) Karmacharya, Rakesh (MGH) Rotenberg, Alex (BCH/Neurology) Anderson, Matthew (BIDMC) Do, Michael (BCH—Neurobio) Khurana, Vikram (BWH) Sabatini, Bernardo (HMS/Neurobio) Anthony, Todd (BCH/Neurobio) Dong, Min (BCH) Kim, Kwang-Soo (McLean) Sahay, Amar (MGH) Arlotta, Paola (Harvard/SCRB) Drugowitsch, Jan (HMS/Neurobio) Kocsis, Bernat (BIDMC) Sahin, Mustafa (BCH/Neurobio) Assad, John (HMS/Neurobio) Dulac, Catherine (Harvard/MCB) Kreiman, Gabriel (BCH/Neurobio) Samuel, Aravi (Harvard/ Physics) Bacskai, Brian (MGH/East) Dymecki, Susan(HMS/Genetics) LaVoie, Matthew (BWH) Sanes, Joshua (Harvard/MCB) Baker, Justin (McLean) Engert, Florian (Harvard/MCB) Lee, Wei-Chung (BCH/Neurobio) Saper, Clifford -
Oup Cercor Bhx026 3790..3805 ++
Cerebral Cortex, July 2017;27: 3790–3805 doi: 10.1093/cercor/bhx026 Advance Access Publication Date: 10 February 2017 Original Article ORIGINAL ARTICLE Body Topography Parcellates Human Sensory and Motor Cortex Esther Kuehn1,2,3,4, Juliane Dinse5,6,†, Estrid Jakobsen7, Xiangyu Long1, Andreas Schäfer5, Pierre-Louis Bazin1,5, Arno Villringer1, Martin I. Sereno2 and Daniel S. Margulies7 1Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig 04103, Germany, 2Department of Psychology and Language Sciences, University College London, London WC1H 0DG, UK, 3Center for Behavioral Brain Sciences Magdeburg, Magdeburg 39106, Germany, 4Aging and Cognition Research Group, DZNE, Magdeburg 39106, Germany, 5Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig 04103, Germany, 6Faculty of Computer Science, Otto-von- Guericke University, Magdeburg 39106, Germany and 7Max Planck Research Group for Neuroanatomy & Connectivity, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig 04103, Germany Address correspondence to Esther Kuehn, Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig 04103, Germany. Email: [email protected] † Co-first author. Abstract The cytoarchitectonic map as proposed by Brodmann currently dominates models of human sensorimotor cortical structure, function, and plasticity. According to this model, primary motor cortex, area 4, and primary somatosensory cortex, area 3b, are homogenous areas, with the major division lying between the two. Accumulating empirical and theoretical evidence, however, has begun to question the validity of the Brodmann map for various cortical areas. Here, we combined in vivo cortical myelin mapping with functional connectivity analyses and topographic mapping techniques to reassess the validity of the Brodmann map in human primary sensorimotor cortex. -
COLUMBIA Columbia University DIGITAL KNOWLEDGE VENTURES
COLUMBIA columbia university DIGITAL KNOWLEDGE VENTURES Brain and Mind May 13, 2004 Gerald D. Fischbach, MD Neuroscience and Neuropathology—Converging Streams Introduction by Lee Bollinger President Lee Bollinger: This symposium is the result of the very, very hard work of Professor Tom Jessell and Dr. Joanna Rubinstein, and I want to thank and acknowledge them, and would like to thank all of you for coming. This is a great testament to the general perceived importance of the subjects of this symposium. I want to thank all the speakers who have come to participate. I want to take this occasion just to announce that Columbia will be launching—we are launching, as of this moment—an institute for neuroscience that will be part (eventually) of the major center for the study of the brain and behavior. We all, I think, recognize in the academy the extraordinary advances that have come just in the past few decades, the past decade in particular, because of the discoveries around the genetic code. Where that will take us of course we don't know, and we're making very, very significant investments across the country in trying to advance knowledge as a result of that new knowledge. But the study of the brain and how it works is clearly central not only to the curing of disease, but also to the understandings that we bring to every, virtually every, area of life: social sciences, the professions, and the humanities. And it is Columbia's goal to try to bring as many scientific advances as we possibly can to this area, and also to integrate it with other areas of knowledge.