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The Dopamine Transporter: More Exciting Than Housekeeping
The Dopamine Transporter: More Exciting than Housekeeping Susan Ingram Washington State University Vancouver Dopaminergic Synapse Presynaptic cell MGluR 2 Na+ Cl- GIRK D2 DA DA D2 D1 a1 Postsynaptic cell Currents are activated at lower dopamine concentrations than are required for transport Ingram, et al., 2002 Low DA concentrations increase firing Ingram, et al., 2002 DAT-mediated chloride current is excitatory in cultured midbrain DA neurons DEPOLARIZATION HYPERPOLARIZATION Ingram, et al., 2002 Proteins that regulate intracellular Cl- Whole-cell patch clamp recordings from DA neurons Raclopride Sulpiride Prazosin TTX biocytin Prasad and Amara, 2001 Amphetamine activates a DAT-mediated current at low concentrations Cultures Slices Watts, Fyfe and Ingram, unpublished data. DA neurons make glutamatergic autapses in culture and amphetamine increases AMPA currents Ingram, et al., unpublished data mbYFPQS localizes to the membrane of cultured midbrain neurons Watts, Jimenez and Ingram, unpublished data. Amphetamine stimulates a dose-dependent change in mbYFPQS fluorescence in both soma and dendrites of DA neurons Watts and Ingram, unpublished data. KCC2 Expression is different in cultures and slices cultures slices TH KCC2 Jamieson and Ingram, unpublished data. Baculoviral Transfections Watts and Ingram, unpublished data. Summary • DAT-mediated chloride current may alter excitability of DA neurons and integration of synaptic activity. • The current may be activated selectively (relative to transport) by low DA and amphetamine concentrations suggesting a role in increasing release of DA. • The amphetamine-mediated current is dose-dependent in both cultures and slices of midbrain neurons but is inhibited at high amphetamine concentrations (20 µM). • The mbYFPQS is a sensitive tool to measure intracellular chloride concentrations (K50 = 30 mM) and is useful for monitoring changes in intracellular chloride concentrations in dendrites. -
Program Book
PARKINSON’SDISEASE2014 ADVANCING RESEARCH, IMPROVING LIVES PROGRAM MATERIALS Sponsored by: January 6 – 7, 2014 Natcher Conference Center National Institutes of Health Bethesda, MD About our cover: The program cover image is a stylized version of the Parkinson’s Disease Motor-Related Pattern (PDRP), an abnormal pattern of regional brain function observed in MRI studies which shows increased metabolism indicated by red in some brain regions (pallidothalamic, pontine, and motor cortical areas), and decreased metabolism indicated by blue in others (associated lateral premotor and posterior parietal areas). Original image used with permission of David Eidelberg, M.D. For further information see: Hirano et al., Journal of Neuroscience 28 (16): 4201-4209. Welcome Message from Dr. Story C. Landis Welcome to the National Institute of Neurological Disorders and Stroke (NINDS) conference, “Parkinson’s Disease 2014: Advancing Research, Improving Lives.” Remarkable new discoveries and technological advances are rapidly changing the way we study the biological mechanisms of Parkinson’s disease, identify paths to improved treatments, and design effective clinical trials. Elucidating mechanisms and developing and testing effective interventions require a diverse set of approaches and perspectives. The NINDS has organized this conference with the primary goal of seeking consensus on, and prioritizing, research recommendations spanning clinical, translational, and basic Parkinson’s disease research that we support. We have assembled a stellar and dedicated group of session chairs and panelists who have worked collaboratively to identify emerging research opportunities in Parkinson’s research. While we have divided our working groups into three main research areas, we expect each will inform the others over the course of the next two days, and we look forward to both complementary and unique perspectives. -
Isoflurane Inhibits Dopaminergic Synaptic Vesicle Exocytosis Coupled to Cav2.1 and Cav2.2 in Rat Midbrain Neurons
This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. Research Article: New Research | Neuronal Excitability Isoflurane inhibits dopaminergic synaptic vesicle exocytosis coupled to CaV2.1 and CaV2.2 in rat midbrain neurons Christina L. Torturo1,2, Zhen-Yu Zhou1, Timothy A. Ryan1,3 and Hugh C. Hemmings1,2 1Departments of Anesthesiology, Weill Cornell Medicine, New York, NY 10065 2Pharmacology, Weill Cornell Medicine, New York, NY 10065 3Biochemistry, Weill Cornell Medicine, New York, NY 10065 https://doi.org/10.1523/ENEURO.0278-18.2018 Received: 16 July 2018 Revised: 18 December 2018 Accepted: 21 December 2018 Published: 10 January 2019 Author Contributions: CLT, ZZ, TAR and HCH designed the research; CLT performed the research, TAR contributed unpublished reagents/analytic tools; CLT and ZZ analyzed the data; CLT, ZZ, TAR, and HCH wrote the paper. Funding: http://doi.org/10.13039/100000002HHS | National Institutes of Health (NIH) GM58055 Conflict of Interest: HCH: Editor-in-Chief of the British Journal of Anaesthesia; consultant for Elsevier. Funding Sources: NIH GM58055 Corresponding author: Hugh C. Hemmings, E-mail: [email protected] Cite as: eNeuro 2019; 10.1523/ENEURO.0278-18.2018 Alerts: Sign up at www.eneuro.org/alerts to receive customized email alerts when the fully formatted version of this article is published. Accepted manuscripts are peer-reviewed but have not been through the copyediting, formatting, or proofreading process. Copyright © 2019 Torturo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. -
Fall 2014 Columbia Magazine Collaborations 45 Startups
FALL 2014 COLUMBIA MAGAZINE COLLABORATIONS 45 STARTUPS. 1 GARAGE. C1_FrontCover_v1.indd C1 10/1/14 4:41 PM ChangeCHANGETHEWORLD lives, On October 29, join Columbians around the globe for 24 hours of giving back, connecting, and chances to win matching funds for your favorite school or program. Changing Lives That Change The World givingday.columbia.edu #ColumbiaGivingDay C2_GivingDay.indd C2 9/30/14 5:45 PM CONTENTS Fall 2014 12 44 26 DEPARTMENTS FEATURES 3 Letters 12 Start Me Up By Rebecca Shapiro 6 Primary Sources The new Columbia Startup Lab in SoHo is open Darwin in plain English . Gail Sheehy’s New York for business. We visit some young entrepreneurs to memories . Eric Holder goes to Ferguson see what clicks. 8 College Walk 22 Streams and Echoes Grab your coat and get your stethoscope . By Tim Page Decanterbury tales . Kenneth Waltz: The composer Chou Wen-chung, featured this fall as one A remembrance of the Miller Theatre’s “Composer Portraits,” has been connecting East and West for more than sixty years. 48 News Amale Andraos named dean of GSAPP . 26 The Professor’s Last Stand Columbia gives seed grants to overseas research By David J. Craig projects . Brown Institute for Media Innovation US historian Eric Foner is trying something new before opens its doors . Columbia Secondary School he retires: he’s fi lming a massive open online course, graduates its fi rst class . David Goldstein or MOOC. Call it a Lincoln login. recruited to head new genomics institute . Bollinger’s term extended 34 Rewired By Paul Hond 53 Newsmakers Law professor Tim Wu, the coiner of “net neutrality,” entered New York’s lieutenant-governor race to change 55 Explorations politics. -
Development of a Lab-On-A-Chip Device for Rapid Nanotoxicity Assessment in Vitro Pratikkumar Shah Engineering, [email protected]
Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 12-11-2014 Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro Pratikkumar Shah Engineering, [email protected] DOI: 10.25148/etd.FI15032160 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Analytical Chemistry Commons, Bioelectrical and Neuroengineering Commons, Biomedical Devices and Instrumentation Commons, Electronic Devices and Semiconductor Manufacturing Commons, Molecular, Cellular, and Tissue Engineering Commons, and the Nanotechnology Fabrication Commons Recommended Citation Shah, Pratikkumar, "Development of a Lab-on-a-Chip Device for Rapid Nanotoxicity Assessment In Vitro" (2014). FIU Electronic Theses and Dissertations. 1834. https://digitalcommons.fiu.edu/etd/1834 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida DEVELOPMENT OF A LAB-ON-A-CHIP DEVICE FOR RAPID NANOTOXICITY ASSESSMENT IN VITRO A dissertation submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY in BIOMEDICAL ENGINEERING by Pratikkumar Shah 2015 To: Dean Amir Mirmiran College of Engineering and Computing This dissertation, written by Pratikkumar Shah, and entitled Development of a Lab-on-a- Chip Device for Rapid Nanotoxicity Assessment In Vitro, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this dissertation and recommend that it be approved. -
Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of Dopamine Synthesis
The Journal of Neuroscience, October 15, 2002, 22(20):8951–8960 Methamphetamine-Induced Degeneration of Dopaminergic Neurons Involves Autophagy and Upregulation of Dopamine Synthesis Kristin E. Larsen,1 Edward A. Fon,2 Teresa G. Hastings,3 Robert H. Edwards,4 and David Sulzer1 1Departments of Neurology and Psychiatry, Columbia University, and Department of Neuroscience, New York Psychiatric Institute, New York, New York 10032, 2Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada, 3Departments of Neuroscience and Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, and 4Departments of Neurology and Physiology, University of California, San Francisco, California 94143 Methamphetamine (METH) selectively injures the neurites of pression. METH administration also promoted the synthesis of dopamine (DA) neurons, generally without inducing cell death. It DA via upregulation of tyrosine hydroxylase activity, resulting in has been proposed that METH-induced redistribution of DA an elevation of cytosolic DA even in the absence of vesicular from the vesicular storage pool to the cytoplasm, where DA can sequestration. Electron microscopy and fluorescent labeling oxidize to produce quinones and additional reactive oxygen confirmed that METH promoted the formation of autophagic species, may account for this selective neurotoxicity. To test granules, particularly in neuronal varicosities and, ultimately, this hypothesis, we used mice heterozygous (ϩ/Ϫ) or homozy- within cell bodies of dopaminergic neurons. Therefore, we pro- gous (Ϫ/Ϫ) for the brain vesicular monoamine uptake trans- pose that METH neurotoxicity results from the induction of a porter VMAT2, which mediates the accumulation of cytosolic specific cellular pathway that is activated when DA cannot be DA into synaptic vesicles. -
Mens Rea and Methamphetamine: High Time for a Modern Doctrine Acknowledging the Neuroscience of Addiction
Fordham Law Review Volume 85 Issue 5 Article 20 2017 Mens Rea and Methamphetamine: High Time for a Modern Doctrine Acknowledging the Neuroscience of Addiction Meredith Cusick Fordham University School of Law Follow this and additional works at: https://ir.lawnet.fordham.edu/flr Part of the Criminal Law Commons Recommended Citation Meredith Cusick, Mens Rea and Methamphetamine: High Time for a Modern Doctrine Acknowledging the Neuroscience of Addiction, 85 Fordham L. Rev. 2417 (2017). Available at: https://ir.lawnet.fordham.edu/flr/vol85/iss5/20 This Note is brought to you for free and open access by FLASH: The Fordham Law Archive of Scholarship and History. It has been accepted for inclusion in Fordham Law Review by an authorized editor of FLASH: The Fordham Law Archive of Scholarship and History. For more information, please contact [email protected]. MENS REA AND METHAMPHETAMINE: HIGH TIME FOR A MODERN DOCTRINE ACKNOWLEDGING THE NEUROSCIENCE OF ADDICTION Meredith Cusick* In American criminal law, actus non facit reum, nisi mens sit rea, “an act does not make one guilty, without a guilty mind.” Both actus reus and mens rea are required to justify criminal liability. The Model Penal Code’s (MPC) section on culpability has been especially influential on mens rea analysis. An issue of increasing importance in this realm arises when an offensive act is committed while the actor is under the influence of drugs. Several legal doctrines address the effect of intoxication on mental state, including the MPC, limiting or eliminating its relevance to the mens rea analysis. Yet these doctrines do not differentiate between intoxication and addiction. -
Arxiv:2107.12536V2 [Q-Bio.NC] 1 Sep 2021
ADATA-DRIVEN BIOPHYSICAL COMPUTATIONAL MODEL OF PARKINSON’S DISEASE BASED ON MARMOSET MONKEYS Caetano M. Ranieri Jhielson M. Pimentel Institute of Mathematical and Computer Sciences Edinburgh Centre for Robotics University of Sao Paulo Heriot-Watt University Sao Carlos, SP, Brazil Edinburgh, Scotland, UK [email protected] [email protected] Marcelo R. Romano Leonardo A. Elias School of Electrical and Computer Engineering School of Electrical and Computer Engineering University of Campinas University of Campinas Campinas, SP, Brazil Campinas, SP, Brazil [email protected] [email protected] Roseli A. F. Romero Michael A. Lones Institute of Mathematical and Computer Sciences Edinburgh Centre for Robotics University of Sao Paulo Heriot-Watt University Sao Carlos, SP, Brazil Edinburgh, Scotland, UK [email protected] [email protected] Mariana F. P. Araujo Patricia A. Vargas Health Sciences Centre Edinburgh Centre for Robotics Federal University of Espirito Santo Heriot-Watt University Vitoria, ES, Brazil Edinburgh, Scotland, UK [email protected] [email protected] Renan C. Moioli Digital Metropolis Institute Federal University of Rio Grande do Norte Natal, RN, Brazil [email protected] September 2, 2021 arXiv:2107.12536v2 [q-bio.NC] 1 Sep 2021 ABSTRACT In this work we propose a new biophysical computational model of brain regions relevant to Parkin- son’s Disease (PD) based on local field potential data collected from the brain of marmoset monkeys. Parkinson’s disease is a neurodegenerative disorder, linked to the death of dopaminergic neurons at the substantia nigra pars compacta, which affects the normal dynamics of the basal ganglia-thalamus- cortex (BG-T-C) neuronal circuit of the brain. -
Fonction Et Dysfonction Dans La Maladie De Parkinson
THESE DE DOCTORAT DE L’UNIVERSITE PIERRE ET MARIE CURIE École doctorale n°158 Cerveau, Cognition, et Comportement Présentée et soutenue par Evinaa SELLAIAH pour obtenir le titre de DOCTEUR DE L’UNIVERSITE PIERRE ET MARIE CURIE Spécialité : Neurosciences Le noyau subthalamique et le contrôle moteur : Fonction et dysfonction dans la maladie de Parkinson soutenue le 24 novembre 2017 Jury : Président : M. Bernard PIDOUX - Université Pierre et Marie Curie, Paris, France Rapporteur : Mme. Patricia LIMOUSIN - University College London, Londres, Royaume-Uni Rapporteur : M. Paul SAULEAU - Institut des Neurosciences Cliniques de Rennes, France Examinateur : M. Stéphane DERREY - Département de Neurochirurgie, CHU de Rouen, France Examinateur : M. Laurent VENANCE - Collège de France, Paris, France Directrice de thèse : Mme Carine KARACHI - Institut du Cerveau et de la Moelle Épinière, Paris, France Remerciements *** Je ne pourrai commencer cette thèse sans une page dédiée aux remerciements, ce sera certainement la page la plus lue de tout mon manuscrit! Je remercie tout particulièrement Monsieur Dufloux, de m’avoir permis de réaliser ce travail de recherche. Merci à Carine Karachi pour m’avoir encadrée, conseillée, soutenue, supportée tout au long de ce travail, et pour tes multiples relectures de ce manuscrit. Merci à Brian Lau pour m’avoir accueillie dans l’équipe, encadrée, et aidée pour les analyses électrophysiologiques et statistiques. Je remercie chaleureusement les membres du jury pour l’honneur qu’ils me font de consacrer une partie de leur temps pour juger ce travail. Je remercie Nathalie Georges pour les multiples relectures de ce manuscrit et l’aide ap- portée dans les analyses. Un grand merci à Marie-Laure Welter, qui m’a fait découvrir la recherche clinique et la maladie de Parkinson d’un point de vue clinique. -
Roles for -Synuclein in Gene Expression
G C A T T A C G G C A T genes Review Roles for α-Synuclein in Gene Expression Mahalakshmi Somayaji 1, Zina Lanseur 1, Se Joon Choi 1, David Sulzer 1,2 and Eugene V. Mosharov 1,2,* 1 Departments of Psychiatry and Neurology, Columbia University Medical Center, New York, NY 10032, USA; [email protected] (M.S.); [email protected] (Z.L.); [email protected] (S.J.C.); [email protected] (D.S.) 2 Division of Molecular Therapeutics, New York State Psychiatric Institute, Research Foundation for Mental Hygiene, New York, NY 10032, USA * Correspondence: [email protected] Abstract: α-Synuclein (α-Syn) is a small cytosolic protein associated with a range of cellular com- partments, including synaptic vesicles, the nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, and lysosomes. In addition to its physiological role in regulating presynaptic function, the protein plays a central role in both sporadic and familial Parkinson’s disease (PD) via a gain-of- function mechanism. Because of this, several recent strategies propose to decrease α-Syn levels in PD patients. While these therapies may offer breakthroughs in PD management, the normal functions of α-Syn and potential side effects of its depletion require careful evaluation. Here, we review recent evidence on physiological and pathological roles of α-Syn in regulating activity-dependent signal transduction and gene expression pathways that play fundamental role in synaptic plasticity. Keywords: Parkinson’s disease; α-Synuclein; gene expression; signal transduction; epigenetics; silencing therapeutics; nuclear receptors; calcium channels Citation: Somayaji, M.; Lanseur, Z.; Choi, S.J.; Sulzer, D.; Mosharov, E.V. -
Elemental and Neurochemical Based Analysis of the Pathophysiological Mechanisms of Gilles De La Tourette Syndrome
MEDIZINISCHE HOCHSCHULE HANNOVER Klinik für Psychiatrie, Sozialpsychiatrie und Psychotherapie Elemental and Neurochemical Based Analysis of the Pathophysiological Mechanisms of Gilles de la Tourette syndrome INAUGURALDISSERTATION zur Erlangung des Grades einer Doktorin oder eines Doktors der Naturwissenschaften Doctor rerum naturalium - Dr. rer. nat. vorgelegt von Ahmad Seif Kanaan B.Sc., M.Sc geb. am 17/05/1986, Amman, Jordanien Hannover, Deutschland (2017) Promotionsordnung der Medizinischen Hochschule Hannover für die Erlangung des Grades einer Doktorin/eines Doktors der Naturwissenschaften (Doctor rerum naturalium) Letzte Änderung in der 523. Sitzung Senatssitzung vom 15.07.2015 Wissenschaftliche Betreuung: Prof. Dr. med. Kirsten Müller-Vahl Wissenschaftliche Zweitbetreuung: Prof. Dr. rer. nat. Claudia Grothe 1. Erst-Gutachterin/Gutachter: Prof. Dr. med. Kirsten Müller-Vahl 2. Gutachterliche Stellungnahme durch: Prof. Dr. rer. nat. Claudia Grothe 3. Gutachterin/Gutachter: Prof Dr. Phil. Florian Beißner Tag der mündlichen Prüfung: 12.07.2017 Promotionsordnung der Medizinischen Hochschule Hannover für die Erlangung des Grades einer Doktorin/eines Doktors der Naturwissenschaften (Doctor rerum naturalium) Letzte Änderung in der 523. Sitzung Senatssitzung vom 15.07.2015 To Seif, Shireen, Farah & Mira . “How can a three-pound mass of jelly that you can hold in your palm imagine angels, contemplate the meaning of infinity, and even question its own place in the cosmos? Especially awe inspiring is the fact that any single brain, including yours, is made up of atoms that were forged in the hearts of countless, far-flung stars billions of years ago. These particles drifted for eons and light-years until gravity and change brought them together here, now. These atoms now form a conglomerate- your brain- that can not only ponder the very stars that gave it birth but can also think about its own ability to think and wonder about its own ability to wonder. -
10 Major Discoveries in 2014 by NARSAD Grantees
10 Major Discoveries in 2014 Insert_Layout 1 2/4/15 11:33 AM Page 1 10 Major Discoveries in 2014 by NARSAD Grantees Potential Diagnostic Biomarker: Depression New Brain Biomarker Found for Depression Risk in Young Children Deanna M. Barch, Ph.D. Dr. Barch and colleagues including former grantees Joan Luby, M.D. and Kelly Botteron, M.D. Washington University discovered the first-ever structural brain biomarker to predict a small child’s risk of having School of Medicine, St. Louis recurrent major depression. They used MRI scans to measure a brain area called the anterior 2013 NARSAD insula (AI). In children at high risk for recurrent major depression (MDD), the volume of the Distinguished Investigator Grant AI was smaller than normal. The effect was especially notable in children who, before reaching school age, had experienced abnormally strong feelings of guilt. Journal: JAMA Psychiatry, November 12, 2014 Joseph Buxbaum, Ph.D. Basic Research: Autism, Autism Spectrum Disorder (ASD) Mt. Sinai Hospital Scientific Council Member Most Comprehensive Study of Rare Autism Mutations To Date Two studies of DNA sampled from families with one child with autism spectrum disorder Pamela Sklar, M.D., Ph.D. (ASD)––the largest of such studies to date––provide the most vivid picture so far of autism’s Mt. Sinai Hospital genetic complexity. Together, they identify dozens of genes not previously linked with autism. Scientific Council Member The teams predict that at least 300 rare, non-inherited, or “de novo,” gene mutations will be Matthew State, M.D., Ph.D. found to play a role in causing autism spectrum disorders.