RIM-BP2 Primes Synaptic Vesicles Via Recruitment of Munc13-1 At
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Plp-Positive Progenitor Cells Give Rise to Bergmann Glia in the Cerebellum
Citation: Cell Death and Disease (2013) 4, e546; doi:10.1038/cddis.2013.74 OPEN & 2013 Macmillan Publishers Limited All rights reserved 2041-4889/13 www.nature.com/cddis Olig2/Plp-positive progenitor cells give rise to Bergmann glia in the cerebellum S-H Chung1, F Guo2, P Jiang1, DE Pleasure2,3 and W Deng*,1,3,4 NG2 (nerve/glial antigen2)-expressing cells represent the largest population of postnatal progenitors in the central nervous system and have been classified as oligodendroglial progenitor cells, but the fate and function of these cells remain incompletely characterized. Previous studies have focused on characterizing these progenitors in the postnatal and adult subventricular zone and on analyzing the cellular and physiological properties of these cells in white and gray matter regions in the forebrain. In the present study, we examine the types of neural progeny generated by NG2 progenitors in the cerebellum by employing genetic fate mapping techniques using inducible Cre–Lox systems in vivo with two different mouse lines, the Plp-Cre-ERT2/Rosa26-EYFP and Olig2-Cre-ERT2/Rosa26-EYFP double-transgenic mice. Our data indicate that Olig2/Plp-positive NG2 cells display multipotential properties, primarily give rise to oligodendroglia but, surprisingly, also generate Bergmann glia, which are specialized glial cells in the cerebellum. The NG2 þ cells also give rise to astrocytes, but not neurons. In addition, we show that glutamate signaling is involved in distinct NG2 þ cell-fate/differentiation pathways and plays a role in the normal development of Bergmann glia. We also show an increase of cerebellar oligodendroglial lineage cells in response to hypoxic–ischemic injury, but the ability of NG2 þ cells to give rise to Bergmann glia and astrocytes remains unchanged. -
Control of Synapse Number by Glia Erik M
R EPORTS RGCs (8). Similar results were obtained un- der both conditions. After 2 weeks in culture, Control of Synapse Number we used whole-cell patch-clamp recording to measure the significant enhancement of spon- by Glia taneous synaptic activity by astrocytes (Fig. 1, A and B) (9). In the absence of astroglia, Erik M. Ullian,* Stephanie K. Sapperstein, Karen S. Christopherson, little synaptic activity occurred even when Ben A. Barres RGCs were cultured with their tectal target cells (6). This difference in synaptic activity Although astrocytes constitute nearly half of the cells in our brain, their persisted even after a month in culture, indi- function is a long-standing neurobiological mystery. Here we show by quantal cating that it is not accounted for by a matu- analyses, FM1-43 imaging, immunostaining, and electron microscopy that few rational delay. To examine whether glia reg- synapses form in the absence of glial cells and that the few synapses that do ulate synaptic activity by enhancing postsyn- form are functionally immature. Astrocytes increase the number of mature, aptic responsiveness, we measured the re- functional synapses on central nervous system (CNS) neurons by sevenfold and sponse of RGCs to pulses of L-glutamate are required for synaptic maintenance in vitro. We also show that most syn- applied to the cell somas. Regardless of the apses are generated concurrently with the development of glia in vivo. These presence of glia, RGCs responded with in- data demonstrate a previously unknown function for glia in inducing and ward currents (Fig. 1C) that were blocked by stabilizing CNS synapses, show that CNS synapse number can be profoundly glutamate receptor antagonists (10). -
Identification of Synaptic Proteins and Their Isoform Mrnas In
Proc. Natl. Acad. Sci. USA Vol. 91, pp. 12487-12491, December 1994 Cell Biology Identification of synaptic proteins and their isoform mRNAs in compartments of pancreatic endocrine cells (exocytosis/secretion/insulin/diabetes) GUNILLA JACOBSSON*, ANDREW J. BEANt, RICHARD H. SCHELLERt, LISA JUNTTI-BERGGRENt, JUDE T. DEENEYt, PER-OLOF BERGGRENt AND BJORN MEISTER*§ *Department of Neuroscience and tRolf Luft's Center for Diabetes Research, Department of Molecular Medicine, Karolinska Institute, S-171 77 Stockholm, Sweden; and tDepartment of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Beckman Center, Stanford University, Stanford, CA 94305 Communicated by Tomas Hokfelt, August 30, 1994 ABSTRACT Several proteins that are of importance for clostridial neurotoxins, including tetanus toxin and botuli- membrane trafficking in the nerve terminal have recently been num neurotoxin B, whereas botulinum neurotoxins D and F characterized. We have used Western blot and immunohis- are capable of cleaving both forms of VAMP (10-12). tochemistry to show that synaptotagmin, synaptobrevin/VAMP VAMP-1 and VAMP-2 are encoded by two distinct genes (13) (vesicle-associated membrane protein), SNAP-25 (synaptosom- and are differentially expressed in the nervous system (14). al-associated protein of 25 kDa), and syntaxin proteins are Cellubrevin is a homologue of VAMP, which is present in a present in cells of the islets of Langerhans in the endocrine wide variety of tissues and may be a membrane trafficking pancreas. Synaptotagmin-like immunoreactivity (-LI) was lo- protein of a constitutively recycling pathway (15). calized to granules within the cytoplasm of a few endocrine cells In contrast to synaptotagmin and VAMP, the synaptoso- located in the periphery of the islets, identified as somatostatin- mal-associated protein of 25 kDa (SNAP-25) is located at the containing cells, and in many nerve fibers within the islets. -
Variable Priming of a Docked Synaptic Vesicle PNAS PLUS
Variable priming of a docked synaptic vesicle PNAS PLUS Jae Hoon Junga,b,c, Joseph A. Szulea,c, Robert M. Marshalla,c, and Uel J. McMahana,c,1 aDepartment of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305; bDepartment of Physics, Stanford University School of Humanities and Sciences, Stanford, CA 94305; and cDepartment of Biology, Texas A&M University, College Station, TX 77845 Edited by Thomas S. Reese, National Institutes of Health, Bethesda, MD, and approved January 12, 2016 (received for review November 30, 2015) The priming of a docked synaptic vesicle determines the proba- transition. Biochemical and electrophysiological approaches have bility of its membrane (VM) fusing with the presynaptic membrane provided evidence that priming is mediated by interactions be- (PM) when a nerve impulse arrives. To gain insight into the nature tween the SNARE proteins and their regulators (7, 12–14, 24) and of priming, we searched by electron tomography for structural can involve differences in positioning of docked SVs relative to + relationships correlated with fusion probability at active zones of Ca2 channels (25). Biochemistry has also led to the suggestion axon terminals at frog neuromuscular junctions. For terminals that primed SVs may become deprimed (26). fixed at rest, the contact area between the VM of docked vesicles We have previously shown by electron tomography on frog and PM varied >10-fold with a normal distribution. There was no neuromuscular junctions (NMJs) fixed at rest that there are, for merging of the membranes. For terminals fixed during repetitive docked SVs, variations in the extent of the VM–PM contact area evoked synaptic transmission, the normal distribution of contact and in the length of the several AZM macromolecules linking areas was shifted to the left, due in part to a decreased number of the VM to the PM, the so-called ribs, pegs, and pins (2, 27). -
Molecular Biology of Neuronal Voltage-Gated Calcium Channels
EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 30, No 3, 123-130, September 1998 Molecular biology of neuronal voltage-gated calcium channels Hemin Chin and is capable of directing expression of calcium channel activity in heterologous expression systems. In the central Genetics Research Branch, Division of Basic and Clinical Neuroscience Research, nervous system (CNS), VGCCs are expressed by five National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, distinct a1 subunit genes (α1A, α1B, α1C, α1D and α1E), U.S.A. which exhibit further variations due to alternative splicing of the primary RNA transcripts. The α1C and, α1D su b u n i t Accepted 3 August 1998 genes encode dihydropyridine (DHP)-sensitive L-type channels, while the three other α1 subunit genes (α1A, α1B and α1E) give rise to DHP-insensitive P/Q-, N- and R-type channels, respectively. The α2 and δ s u b u n i t proteins are produced by proteolytic cleavage of a larger precursor produced by the single α2-δ gene (Table 1). Introduction Three alternatively spliced variants of the α2 subunit are expressed in a tissue-specific manner. Two variants Calcium ions are important intracellular messengers have been isolated from the brain and skeletal muscle mediating a number of neuronal functions including neuro- (Kim et al., 1992; Williams et al., 1992), and a distinct transmitter release, neurosecretion, neuronal excitation, third splice variant which is expressed in glial cells has survival of eurons, and regulation of gene expression. been recently identified (Puro et al., 1996). In addition to The entry of calcium across the plasmamembrane in the gene encoding the skeletal muscle β subunit, three response to membrane depolarization or activation of 1 other β subunit genes (β2, β3 and β4) have been isolated neurotransmitter receptors represents a major pathway thus far. -
Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks
The Journal of Neuroscience, March 25, 2020 • 40(13):2663–2679 • 2663 Systems/Circuits Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks Javier Rodriguez-Moreno,1 Cesar Porrero,1 Astrid Rollenhagen,2 Mario Rubio-Teves,1 Diana Casas-Torremocha,1 X Lidia Alonso-Nanclares,3 Rachida Yakoubi,2 XAndrea Santuy,3 XAngel Merchan-Pe´rez,3,5,6 XJavier DeFelipe,3,4,5 Joachim H.R. Lu¨bke,2,7,8* and XFrancisco Clasca1* 1Department of Anatomy and Neuroscience, School of Medicine, Auto´noma de Madrid University, 28029 Madrid, Spain, 2Institute of Neuroscience and Medicine INM-10, Research Centre Ju¨lich GmbH, 52425 Ju¨lich, Germany, 3Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biome´dica, Universidad Polite´cnica de Madrid, Pozuelo de Alarco´n, 28223 Madrid, Spain, 4Instituto Cajal, Consejo Superior de Investigaciones Científicas, Arce 37 28002, Madrid, Spain, 5CIBERNED, Centro de Investigacio´n Biome´dica en Red de Enfermedades Neurodegenerativas, 28031 Madrid, Spain, 6Departamento de Arquitectura y Tecnología de Sistemas Informa´ticos, Universidad Polite´cnica de Madrid. Boadilla del Monte, 28660 Madrid, Spain, 7Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty RWTH University Hospital Aachen, 52074 Aachen, Germany, and 8JARA-Translational Brain Medicine, 52425 Ju¨lich-Aachen, Germany Thalamocortical posterior nucleus (Po) axons innervating the vibrissal somatosensory (S1) and motor (MC) cortices are key links in the brain neuronal network that allows rodents to explore the environment whisking with their motile snout vibrissae. Here, using fine-scale high-end 3D electron microscopy, we demonstrate in adult male C57BL/6 wild-type mice marked differences between MC versus S1 Po synapses in (1) bouton and active zone size, (2) neurotransmitter vesicle pool size, (3) distribution of mitochondria around synapses, and (4) proportion of synapses established on dendritic spines and dendritic shafts. -
Mechanisms of Synaptic Plasticity Mediated by Clathrin Adaptor-Protein Complexes 1 and 2 in Mice
Mechanisms of synaptic plasticity mediated by Clathrin Adaptor-protein complexes 1 and 2 in mice Dissertation for the award of the degree “Doctor rerum naturalium” at the Georg-August-University Göttingen within the doctoral program “Molecular Biology of Cells” of the Georg-August University School of Science (GAUSS) Submitted by Ratnakar Mishra Born in Birpur, Bihar, India Göttingen, Germany 2019 1 Members of the Thesis Committee Prof. Dr. Peter Schu Institute for Cellular Biochemistry, (Supervisor and first referee) University Medical Center Göttingen, Germany Dr. Hans Dieter Schmitt Neurobiology, Max Planck Institute (Second referee) for Biophysical Chemistry, Göttingen, Germany Prof. Dr. med. Thomas A. Bayer Division of Molecular Psychiatry, University Medical Center, Göttingen, Germany Additional Members of the Examination Board Prof. Dr. Silvio O. Rizzoli Department of Neuro-and Sensory Physiology, University Medical Center Göttingen, Germany Dr. Roland Dosch Institute of Developmental Biochemistry, University Medical Center Göttingen, Germany Prof. Dr. med. Martin Oppermann Institute of Cellular and Molecular Immunology, University Medical Center, Göttingen, Germany Date of oral examination: 14th may 2019 2 Table of Contents List of abbreviations ................................................................................. 5 Abstract ................................................................................................... 7 Chapter 1: Introduction ............................................................................ -
Chemical Neurotransmission
Cambridge University Press 978-1-107-02598-1 — Stahl's Essential Psychopharmacology 4th Edition Excerpt More Information Chapter1 Chemical neurotransmission Anatomical versus chemical basis of Beyond the second messenger to a neurotransmission 1 phosphoprotein cascade triggering gene 16 Principles of chemical neurotransmission 5 expression Neurotransmitters 5 How neurotransmission triggers gene 18 Neurotransmission: classic, retrograde, expression 18 and volume 6 Molecular mechanism of gene expression Excitation–secretion coupling 8 Epigenetics 24 Signal transduction cascades 9 What are the molecular mechanisms 24 Overview 9 of epigenetics? Forming a second messenger 11 How epigenetics maintains or changes the status quo 26 Beyond the second messenger to phosphoprotein messengers 13 Summary 26 Modern psychopharmacology is largely the story of neurons, not unlike millions of telephone wires chemical neurotransmission. To understand the actions within thousands upon thousands of cables. The ana- of drugs on the brain, to grasp the impact of diseases tomically addressed brain is thus a complex wiring upon the central nervous system, and to interpret the diagram, ferrying electrical impulses to wherever behavioral consequences of psychiatric medicines, the “wire” is plugged in (i.e., at a synapse). Synapses one must be fluent in the language and principles of canformonmanypartsofaneuron,notjustthe chemical neurotransmission. The importance of this dendrites as axodendritic synapses, but also on the fact cannot be overstated for the student of psychophar- soma as axosomatic synapses, and even at the begin- macology. This chapter forms the foundation for the ning and at the end of axons (axoaxonic synapses) entire book, and the roadmap for one’s journey through (Figure 1-2). -
The Interplay Between Neurons and Glia in Synapse Development And
Available online at www.sciencedirect.com ScienceDirect The interplay between neurons and glia in synapse development and plasticity Jeff A Stogsdill and Cagla Eroglu In the brain, the formation of complex neuronal networks and regulate distinct aspects of synaptic development and amenable to experience-dependent remodeling is complicated circuit connectivity. by the diversity of neurons and synapse types. The establishment of a functional brain depends not only on The intricate communication between neurons and glia neurons, but also non-neuronal glial cells. Glia are in and their cooperative roles in synapse formation are now continuous bi-directional communication with neurons to direct coming to light due in large part to advances in genetic the formation and refinement of synaptic connectivity. This and imaging tools. This article will examine the progress article reviews important findings, which uncovered cellular made in our understanding of the role of mammalian and molecular aspects of the neuron–glia cross-talk that perisynaptic glia (astrocytes and microglia) in synapse govern the formation and remodeling of synapses and circuits. development, maturation, and plasticity since the previ- In vivo evidence demonstrating the critical interplay between ous Current Opinion article [1]. An integration of past and neurons and glia will be the major focus. Additional attention new findings of glial control of synapse development and will be given to how aberrant communication between neurons plasticity is tabulated in Box 1. and glia may contribute to neural pathologies. Address Glia control the formation of synaptic circuits Department of Cell Biology, Duke University Medical Center, Durham, In the CNS, glial cells are in tight association with NC 27710, USA synapses in all brain regions [2]. -
Electrical Synapses and Their Functional Interactions with Chemical Synapses
REVIEWS Electrical synapses and their functional interactions with chemical synapses Alberto E. Pereda Abstract | Brain function relies on the ability of neurons to communicate with each other. Interneuronal communication primarily takes place at synapses, where information from one neuron is rapidly conveyed to a second neuron. There are two main modalities of synaptic transmission: chemical and electrical. Far from functioning independently and serving unrelated functions, mounting evidence indicates that these two modalities of synaptic transmission closely interact, both during development and in the adult brain. Rather than conceiving synaptic transmission as either chemical or electrical, this article emphasizes the notion that synaptic transmission is both chemical and electrical, and that interactions between these two forms of interneuronal communication might be required for normal brain development and function. Communication between neurons is required for Electrical and chemical synapses are now known to brain function, and the quality of such communica- coexist in most organisms and brain structures, but details tion enables hardwired neural networks to act in a of the properties and distribution of these two modalities of dynamic fashion. Functional interactions between transmission are still emerging. Most research efforts neurons occur at anatomically identifiable cellular have focused on exploring the mechanisms of chemi- regions called synapses. Although the nature of synaptic cal transmission, and considerably less is known transmission has been an area of enormous controversy about those underlying electrical transmission. It was (BOX 1), two main modalities of synaptic transmission — thought that electrical synapses were more abundant namely, chemical and electrical — are now recognized. At in invertebrates and cold-blooded vertebrates than chemical synapses, information is transferred through in mammals. -
Liquid-Liquid Phase Separation in Physiology and Pathophysiology of the Nervous System
The Journal of Neuroscience, 0, 2021 • 00(00):000 • 1 Symposium Liquid-Liquid Phase Separation in Physiology and Pathophysiology of the Nervous System Yasunori Hayashi,1 Lenzie K. Ford,2 Luana Fioriti,3 Leeanne McGurk,4 and Mingjie Zhang5,6 1Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan, 2Zuckerman Mind, Brain, Behavior Institute, Columbia University, New York, New York 10027, 3Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Istituto Di Ricovero e Cura a Carattere Scientifico, Milan 20156, Italy, 4Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom, 5Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, China, and 6School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China Molecules within cells are segregated into functional domains to form various organelles. While some of those organelles are delimited by lipid membranes demarcating their constituents, others lack a membrane enclosure. Recently, liquid-liquid phase separation (LLPS) revolutionized our view of how segregation of macromolecules can produce membraneless organelles. While the concept of LLPS has been well studied in the areas of soft matter physics and polymer chemistry, its significance has only recently been recognized in the field of biology. It occurs typically between macromolecules that have multivalent interactions. Interestingly, these features are -
Part III: Modeling Neurotransmission – a Cholinergic Synapse
Part III: Modeling Neurotransmission – A Cholinergic Synapse Operation of the nervous system is dependent on the flow of information through chains of neurons functionally connected by synapses. The neuron conducting impulses toward the synapse is the presynaptic neuron, and the neuron transmitting the signal away from the synapse is the postsynaptic neuron. Chemical synapses are specialized for release and reception of chemical neurotransmitters. For the most part, neurotransmitter receptors in the membrane of the postsynaptic cell are either 1.) channel-linked receptors, which mediate fast synaptic transmission, or 2.) G protein-linked receptors, which oversee slow synaptic responses. Channel-linked receptors are ligand-gated ion channels that interact directly with a neurotransmitter and are called ionotropic receptors. Alternatively, metabotropic receptors do not have a channel that opens or closes but rather, are linked to a G-protein. Once the neurotransmitter binds to the metabotropic receptor, the receptor activates the G-protein which, in turn, goes on to activate another molecule. 3a. Model the ionotropic cholinergic synapse shown below. Be sure to label all of the following: voltage-gated sodium channel, voltage-gated potassium channel, neurotransmitter, synaptic vesicle, presynaptic cell, postsynaptic cell, potassium leak channel, sodium-potassium pump, synaptic cleft, acetylcholine receptor, acetylcholinesterase, calcium channel. When a nerve impulse (action potential) reaches the axon terminal, it sets into motion a chain of events that triggers the release of neurotransmitter. You will next model the events of neurotransmission at a cholinergic synapse. Cholinergic synapses utilize acetylcholine as the chemical of neurotransmission. MSOE Center for BioMolecular Modeling Synapse Kit: Section 3-6 | 1 Step 1 - Action potential arrives at the Step 2 - Calcium channels open in the terminal end of the presynaptic cell.