Astrocyte Induced Synaptic Plasticity
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Deciphering the Physiology Underlying the Rapid Clinical Effects of Perispinal Etanercept in Alzheimer's Disease
Current Alzheimer Research, 2012, 9, 99-109 99 Deciphering the Physiology Underlying the Rapid Clinical Effects of Perispinal Etanercept in Alzheimer’s Disease Edward Tobinick* 100 UCLA Medical Plaza, Suites 205-210, Los Angeles, California 90095, USA Abstract: Excess tumor necrosis factor (TNF) plays a pivotal role in the pathogenesis of Alzheimer’s disease(AD). Clini- cal improvement following perispinal administration of etanercept in patients with Alzheimer’s disease and other forms of dementia and brain dysfunction is characteristically evident within minutes. The rapidity and constellation of the clinical effects across multiple domains (cognition, mood, memory, motor function, and attention) suggest they are mediated by non-synaptic signaling mechanisms previously unrecognized for etanercept. These mechanisms likely extend beyond the known roles of TNF as a gliotransmitter that modulates synaptic strength, synaptic scaling, and AMPA receptor traffick- ing. Preliminary basic science and clinical investigation suggests that perispinal administration of etanercept may lead to its rapid penetration into the cerebrospinal fluid (CSF) within the cerebral ventricles. Diffusion of large molecules into the periventricular brain parenchyma is known to occur, but this process may not be sufficient to explain the rapidity of the clinical effects. There exist populations of cells, including CSF-contacting neurons and modified ependymal cells called tanycytes, that have receptive surfaces in direct contact with the CSF. It is hypothesized that the rapid clinical effects of perispinal etanercept involve non-synaptic signal transduction across the ependymal barrier and into neuronal networks via these CSF-contacting cells. This hypothesis challenges the dogma that penetration of a therapeutic into the cerebral pa- renchyma through the endothelium of the cerebral vasculature (the so-called blood- brain barrier) is necessary to produce rapid clinical effects in AD. -
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). -
Abstract Book
Table of Contents Tuesday, May 25, 2021 ............................................................................................................................................................... 5 T1. Astrocyte-Specific Expression of the Extracellular Matrix Gene HtrA1 Regulates Susceptibility to Stress in a Sex- Specific Manner ....................................................................................................................................................................... 5 T2. Plexin-B2 Regulates Migratory Plasticity of Glioblastoma Cells in a 3D-Printed Micropattern Device ............................. 5 T3. Pathoanatomical Mapping of Differential MAPT Expression and Splicing in Progressive Supranuclear Palsy ............... 5 T4. Behavioral Variability in Response to Chronic Stress and Morphine in BXD and Parental Mouse Lines......................... 6 T5. Thyroid-Stimulating Hormone Receptor Regulates Anxiety .............................................................................................. 6 T6. Drugs That Inhibit Microglial Inflammation Also Ameliorate Aβ1-42 Induced Toxicity in C. Elegans ............................... 7 T7. Phosphodiesterase 1b is an Upstream Regulator of a Key Gene Network in the Nucleus Accumbens Driving Addiction- Like Behaviors ......................................................................................................................................................................... 7 T8. Reduced Gap Effect in Children With FOXP1 Syndrome and Autism Spectrum -
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. -
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]. -
Dietary Fat Exacerbates Postprandial Hypothalamic Inflammation Involving Glial Fibrillary Acidic Protein-Positive Cells and Micr
Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein-positive cells and microglia in male mice Céline Cansell, Katharina Stobbe, Clara Sanchez, Ophélia Le Thuc, Coralie-Anne Mosser, Selma Ben-Fradj, Joris Leredde, Cynthia Lebeaupin, Delphine Debayle, Lucile Fleuriot, et al. To cite this version: Céline Cansell, Katharina Stobbe, Clara Sanchez, Ophélia Le Thuc, Coralie-Anne Mosser, et al.. Di- etary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein- positive cells and microglia in male mice. Glia, Wiley, 2021, 69 (1), pp.42-60. 10.1002/glia.23882. hal-02899910 HAL Id: hal-02899910 https://hal.archives-ouvertes.fr/hal-02899910 Submitted on 5 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Received: 5 December 2019 Revised: 10 June 2020 Accepted: 11 June 2020 DOI: 10.1002/glia.23882 RESEARCH ARTICLE Dietary fat exacerbates postprandial hypothalamic inflammation involving -
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. -
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. -
Synaptophysin Regulates Activity-Dependent Synapse Formation in Cultured Hippocampal Neurons
Synaptophysin regulates activity-dependent synapse formation in cultured hippocampal neurons Leila Tarsa and Yukiko Goda* Division of Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0366 Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved November 20, 2001 (received for review October 29, 2001) Synaptophysin is an abundant synaptic vesicle protein without a homogenotypic syp-mutant cultures, however, synapse forma- definite synaptic function. Here, we examined a role for synapto- tion is similar to that observed for wild-type cultures. Interest- physin in synapse formation in mixed genotype micro-island cul- ingly, the decrease in syp-mutant synapse formation is prevented tures of wild-type and synaptophysin-mutant hippocampal neu- when heterogenotypic cultures are grown in the presence of rons. We show that synaptophysin-mutant synapses are poor tetrodotoxin (TTX) or postsynaptic receptor blockers. Our donors of presynaptic terminals in the presence of competing results demonstrate a role for syp in activity-dependent com- wild-type inputs. In homogenotypic cultures, however, mutant petitive synapse formation. neurons display no apparent deficits in synapse formation com- pared with wild-type neurons. The reduced extent of synaptophy- Materials and Methods sin-mutant synapse formation relative to wild-type synapses in Hippocampal Cultures. Primary cultures of dissociated hippocam- mixed genotype cultures is attenuated by blockers of synaptic pal neurons were prepared from late embryonic (E18–19) or transmission. Our findings indicate that synaptophysin plays a newborn (P1) wild-type and syp-mutant mice as described (10). previously unsuspected role in regulating activity-dependent syn- Briefly, dissected hippocampi were incubated for 30 min in 20 apse formation. -
Astroglial Networks Scale Synaptic Activity and Plasticity
Astroglial networks scale synaptic activity and plasticity Ulrike Pannascha, Lydia Vargováb,c, Jürgen Reingruberd, Pascal Ezana, David Holcmand, Christian Giaumea, Eva Sykováb,c, and Nathalie Rouacha,1 aCenter for Interdisciplinary Research in Biology, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7241/Institut National de la Santé et de la Recherche Médicale U1050, Collège de France, 75005 Paris, France; bDepartment of Neuroscience and Center for Cell therapy and Tissue Repair, Charles University, Second Faculty of Medicine, 150 06 Prague, Czech Republic; cDepartment of Neuroscience, Institute of Experimental Medicine of the Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic; and dInstitut de Biologie de l’Ecole Normale Supérieure, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8197/Institut National de la Santé et de la Recherche Médicale U1024, Department of Computational Biology and Mathematics, Ecole Normale Supérieure, Paris, 75005, France Edited* by Roger A. Nicoll, University of California, San Francisco, CA, and approved April 11, 2011 (received for review November 22, 2010) Astrocytes dynamically interact with neurons to regulate synaptic during synaptic activity. This impairment results in increased transmission. Although the gap junction proteins connexin 30 neuronal excitability, release probability, glutamate spillover, and (Cx30) and connexin 43 (Cx43) mediate the extensive network insertion of postsynaptic AMPARs, unsilencing synapses. Alto- organization of astrocytes, their role in synaptic physiology is un- gether, our findings indicate that gap junction-mediated astroglial known. Here we show, by inactivating Cx30 and Cx43 genes, that networks control synaptic strength by modulating extracellular astroglial networks tone down hippocampal synaptic transmission homeostasis. -
Specific Labeling of Synaptic Schwann Cells Reveals Unique Cellular And
RESEARCH ARTICLE Specific labeling of synaptic schwann cells reveals unique cellular and molecular features Ryan Castro1,2,3, Thomas Taetzsch1,2, Sydney K Vaughan1,2, Kerilyn Godbe4, John Chappell4, Robert E Settlage5, Gregorio Valdez1,2,6* 1Department of Molecular Biology, Cellular Biology, and Biochemistry, Brown University, Providence, United States; 2Center for Translational Neuroscience, Robert J. and Nancy D. Carney Institute for Brain Science and Brown Institute for Translational Science, Brown University, Providence, United States; 3Neuroscience Graduate Program, Brown University, Providence, United States; 4Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, United States; 5Department of Advanced Research Computing, Virginia Tech, Blacksburg, United States; 6Department of Neurology, Warren Alpert Medical School of Brown University, Providence, United States Abstract Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100b+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in *For correspondence: PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC [email protected] differentiation and function.