DOCSLIB.ORG

Differentiation and Characterization of Excitatory and Inhibitory Synapses by Cryo-Electron Tomography and Correlative Microscopy

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Differentiation and Characterization of Excitatory and Inhibitory Synapses by Cryo-Electron Tomography and Correlative Microscopy This Accepted Manuscript has not been copyedited and formatted. The final version may differ from this version. A link to any extended data will be provided when the final version is posted online. Research Articles: Cellular/Molecular Differentiation and characterization of excitatory and inhibitory synapses by cryo-electron tomography and correlative microscopy Chang-Lu Tao1, Yun-Tao Liu1, Rong Sun1, Bin Zhang2, Lei Qi2, Sakar Shivakoti1, Chong-Li Tian2, Peijun Zhang3, Pak-Ming Lau2, Z. Hong Zhou1,4,5 and Guo-Qiang Bi1,6 1National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China 2CAS Key Laboratory of Brain Function and Disease, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China 3Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive Oxford OX37BN, UK 4The California NanoSystems Institute, University of California, Los Angeles, CA 90095, USA 5Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA 6CAS Center for Excellence in Brain Science and Intelligence Technology, and Innovation Center for Cell Signaling Network, University of Science and Technology of China, Hefei, Anhui 230026, China DOI: 10.1523/JNEUROSCI.1548-17.2017 Received: 2 June 2017 Revised: 17 December 2017 Accepted: 24 December 2017 Published: 8 January 2018 Author contributions: C.-L. Tao, Y.-T.L., P.Z., P.-M.L., Z.H.Z., and G.-Q.B. designed research; C.-L. Tao, Y.-T.L., R.S., B.Z., and L.Q. performed research; C.-L. Tao, Y.-T.L., R.S., S.S., C.-L. Tian, and G.-Q.B. analyzed data; C.-L. Tao, Y.-T.L., S.S., P.Z., P.-M.L., Z.H.Z., and G.-Q.B. wrote the paper. Conflict of Interest: The authors declare no competing financial interests. This work was supported in part by grants from the CAS (XDB02050000 to GQB), NSFC (30725017 and 91232722 to GQB; 31070935 to PML), MOST (2009CB941300 to GQB), and NIH (GM071940 to ZHZ). We acknowledge use of instruments at the Center for Integrative Imaging of Hefei National Laboratory for Physical Sciences at the Microscale and those at the Electron Imaging Center for Nanomachines of UCLA supported by NIH (S10RR23057 and S10OD018111) and NSF (DBI-133813). We thank Xiaokang Zhang and Peng Ge for technical advice on imaging and data processing, Jay He for help with design and construction of the cryoCLEM platform, Weidong Yao and Ann Marie Craig for sharing the PSD-95 and mCherrry-gephyrin plasmids, Xiaobing Chen for insightful discussions, Chunhong Qiu for help with illustrations, and the anonymous reviewers for their insightful comments and constructive suggestions to improve the paper. Correspondence: Guo-Qiang Bi, School of Life Science, USTC, 443 Huangshan Rd, Hefei, China, 230027. E-mail: [email protected] and Z. Hong Zhou, The California NanoSystems Institute, UCLA, 570 Westwood Plaza, CA 90095, USA. E-mail: [email protected] Cite as: J. Neurosci ; 10.1523/JNEUROSCI.1548-17.2017 Alerts: Sign up at www.jneurosci.org/cgi/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 © 2018 the authors 1 Differentiation and characterization of excitatory and inhibitory synapses by 2 cryo-electron tomography and correlative microscopy 3 4 Abbreviated title: Visualizing synapse types in 3D by cryoCLEM 5 6 Chang-Lu Tao1,*, Yun-Tao Liu1,*, Rong Sun1, Bin Zhang2, Lei Qi2, Sakar Shivakoti1, 7 Chong-Li Tian2, Peijun Zhang3, Pak-Ming Lau2, Z. Hong Zhou1,4,5,#, Guo-Qiang Bi1,6,# 8 1National Laboratory for Physical Sciences at the Microscale, and School of Life Sciences, 9 University of Science and Technology of China, Hefei, Anhui 230026, China; 2CAS Key 10 Laboratory of Brain Function and Disease, and School of Life Sciences, University of 11 Science and Technology of China, Hefei, Anhui 230026, China; 3Division of Structural 12 Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt 13 Drive Oxford OX37BN, UK; 4The California NanoSystems Institute, University of 14 California, Los Angeles, CA 90095, USA; 5Department of Microbiology, Immunology and 15 Molecular Genetics, University of California, Los Angeles, CA 90095, USA; 6CAS Center 16 for Excellence in Brain Science and Intelligence Technology, and Innovation Center for 17 Cell Signaling Network, University of Science and Technology of China, Hefei, Anhui 18 230026, China 19 *These authors contributed equally to this work. 20 #Correspondence: Guo-Qiang Bi, School of Life Science, USTC, 443 Huangshan Rd, 21 Hefei, China, 230027. E-mail: [email protected] and Z. Hong Zhou, The California 22 NanoSystems Institute, UCLA, 570 Westwood Plaza, CA 90095, USA. E-mail: 23 [email protected]. 24 Number of text pages: 51; Number of figures: 9; Number of movies: 5; 1 25 Number of words: Abstract (215); Significance Statement (118); Introduction (640); 26 Discussion (1207). 27 28 Conflict of Interest: The authors declare no competing financial interests. 29 30 Acknowledgements: This work was supported in part by grants from the CAS 31 (XDB02050000 to GQB), NSFC (30725017 and 91232722 to GQB; 31070935 to PML), 32 MOST (2009CB941300 to GQB), and NIH (GM071940 to ZHZ). We acknowledge use of 33 instruments at the Center for Integrative Imaging of Hefei National Laboratory for Physical 34 Sciences at the Microscale and those at the Electron Imaging Center for Nanomachines 35 of UCLA supported by NIH (S10RR23057 and S10OD018111) and NSF (DBI-133813). 36 We thank Xiaokang Zhang and Peng Ge for technical advice on imaging and data 37 processing, Jay He for help with design and construction of the cryoCLEM platform, 38 Weidong Yao and Ann Marie Craig for sharing the PSD-95 and mCherrry-gephyrin 39 plasmids, Xiaobing Chen for insightful discussions, Chunhong Qiu for help with 40 illustrations, and the anonymous reviewers for their insightful comments and constructive 41 suggestions to improve the paper. 42 43 2 44 Abstract 45 As key functional units in neural circuits, different types of neuronal synapses play distinct 46 roles in brain information processing, learning and memory. Synaptic abnormalities are 47 believed to underlie various neurological and psychiatric disorders. Here, by combining 48 cryo-electron tomography and cryo-correlative light and electron microscopy, we 49 distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, 50 and visualized the in situ three-dimensional organization of synaptic organelles and 51 macromolecules in their native state. Quantitative analyses of over a hundred synaptic 52 tomograms reveal that excitatory synapses contain a mesh-like postsynaptic density 53 (PSD) with thickness ranging from 20-50 nm. In contrast, the PSD in inhibitory synapses 54 assumes a thin sheet-like structure ~12 nm from the postsynaptic membrane. On the 55 presynaptic side, spherical synaptic vesicles (SVs) of 25-60 nm diameter and 56 discus-shaped ellipsoidal SVs of various sizes coexist in both synaptic types, with more 57 ellipsoidal ones in inhibitory synapses. High-resolution tomograms obtained using a Volta 58 phase plate and electron filtering and counting reveal glutamate receptor-like and GABAA 59 receptor-like structures that interact with putative scaffolding and adhesion molecules, 60 reflecting details of receptor anchoring and PSD organization. These results provide an 61 updated view of the ultrastructure of excitatory and inhibitory synapses, and demonstrate 62 the potential of our approach to gain insight into the organizational principles of cellular 63 architecture underlying distinct synaptic functions. 64 3 65 Significance Statement 66 To understand functional properties of neuronal synapses, it is desirable to analyze their 67 structure at molecular resolution. We have developed an integrative approach combining 68 cryoET and correlative fluorescence microscopy to visualize 3D ultrastructural features of 69 intact excitatory and inhibitory synapses in their native state. Our approach shows that 70 inhibitory synapses contain uniform thin sheet-like PSDs, while excitatory synapses 71 contain previously known mesh-like PSDs. We discovered “discus-shaped” ellipsoidal 72 synaptic vesicles, and their distributions along with regular spherical vesicles in synaptic 73 types are characterized. High-resolution tomograms further allowed identification of 74 putative neurotransmitter receptors and their heterogeneous interaction with synaptic 75 scaffolding proteins. The specificity and resolution of our approach enables precise in situ 76 analysis of ultrastructural organization underlying distinct synaptic functions. 77 4 78 Introduction 79 Chemical synapses are basic functional units in neural circuits for information 80 transmission, processing and storage (Eccles, 1964; Sudhof and Malenka, 2008; Mayford 81 et al., 2012). From the enormous number of synapses in the brain, the plasticity of each 82 synapse, and the molecular and functional diversity across these synapses, arise the 83 brain’s remarkable computational power and cognitive capacity (Milner et al., 1998; Bi 84 and Poo, 2001). Glutamatergic and GABAergic synapses, the two main types of central 85 synapses, play opposite roles in excitation and inhibition. They have been shown by 86 biochemical and electrophysiological
Load more

Recommended publications
  • A Guide to Glutamate Receptors
    A guide to glutamate receptors 1 Contents Glutamate receptors . 4 Ionotropic glutamate receptors . 4 - Structure ........................................................................................................... 4 - Function ............................................................................................................ 5 - AMPA receptors ................................................................................................. 6 - NMDA receptors ................................................................................................. 6 - Kainate receptors ............................................................................................... 6 Metabotropic glutamate receptors . 8 - Structure ........................................................................................................... 8 - Function ............................................................................................................ 9 - Group I: mGlu1 and mGlu5. .9 - Group II: mGlu2 and mGlu3 ................................................................................. 10 - Group III: mGlu4, mGlu6, mGlu7 and mGlu8 ............................................................ 10 Protocols and webinars . 11 - Protocols ......................................................................................................... 11 - Webinars ......................................................................................................... 12 References and further reading . 13 Excitatory synapse pathway
    [Show full text]
  • 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].
    [Show full text]
  • PRESYNAPTIC Α2δ SUBUNITS ARE KEY ORGANIZERS of GLUTAMATERGIC SYNAPSES Clemens L
    bioRxiv preprint doi: https://doi.org/10.1101/826016; this version posted October 31, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. PRESYNAPTIC α2δ SUBUNITS ARE KEY ORGANIZERS OF GLUTAMATERGIC SYNAPSES Clemens L. Schöpf1, Stefanie Geisler1, Ruslan I. Stanika1, Marta Campiglio1, Walter A. Kaufmann3, Benedikt Nimmervoll1, Bettina Schlick1, Ryuichi Shigemoto3, and Gerald J. Obermair1,2* From Division of Physiology, Medical University Innsbruck, A-6020 Innsbruck1, Division Physiology, Karl Landsteiner University of Health Sciences, A-3500 Krems2, and Institute of Science and Technology Austria, A-3400 Klosterneuburg3, Austria. Running head: Presynaptic α2δ subunits organize synapses Address correspondence to: *Gerald J. Obermair, Univ.-Prof. Dr., Phone: +43-2732-72090490, E-mail: [email protected], [email protected] In nerve cells the genes encoding for α2δ the auxiliary β and α2δ subunits. α2δ subunits, the subunits of voltage-gated calcium channels targets of the widely prescribed anti-epileptic and (VGCCs) have been linked to synaptic functions anti-allodynic drugs gabapentin and pregabalin, are and neurological disease. Here we show that α2δ membrane-anchored extracellular glycoproteins, subunits are essential for the formation and which modulate VGCC trafficking and calcium organization of glutamatergic synapses. Using a currents (Arikkath and Campbell, 2003; Dolphin, cellular α2δ subunit triple loss-of-function model, 2013; Geisler et al., 2015; Obermair et al., 2008; we demonstrate a failure in presynaptic Zamponi et al., 2015).
    [Show full text]
  • Neural Control and Neuromodulationof Lower Urinary
    Neural Control and Neuromodulation of Lower Urinary Tract Function William C. de Groat University of Pittsburgh Topics • Anatomy and functions of the lower urinary tract • Peripheral innervation (efferent and afferent nerves) • Central neural control of the lower urinary tract • Lower urinary tract dysfunction • Treatment of dysfunction (neuromodulation) • Research opportunities Anatomy and Functions of the Lower Urinary Tract Functions Two Types of Voiding 1. Urine storage - Reservoir: Bladder INVOLUNTARY (Reflex) (infant & fetus) Defect in 2. Urine release Maturation Maturation - Outlet: Urethra INVOLUNTARY THERAPY VOLUNTARY (Reflex) (adult) (adult) Bladder Parkinson’s, MS, stroke, brain tumors, spinal cord injury, Urethra aging, cystitis Lower Urinary Tract Innervation Two Types of Visceral Afferent Neurons: Bladder & Bowel Aδ-fibers responsible for normal bladder sensations C-fibers contribute to urgency, frequency and incontinence Afferent Sensitivity may be Influenced by Substances Released from the Urothelium Aδ fiber C fiber X CNS Urothelium The Bladder U rothelium Glycosaminoglycan Layer Uroplakin Plaques and Discoidal Vesicles r=_zo_"_"l_a_o_cc-lu---.dens } Umbrella Cell Stratum Intermediate Cell Stratum } Basal Cell Stratum Afferent Nerve fiber Urothelial-Afferent Interactions ( I ( I ( I ( ' ( I ( I ( I Urothelium ( I ( 0 I I I AChR ATP, NO, NKA, ACh, NGF ~erves ' Efferent ' nerves nerves Interaction of Sensory Pathways of Multiple Pelvic Organs Convergent Dichotomizing Branch Bladder point Colon Somatic and Visceral Afferent
    [Show full text]
  • 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.
    [Show full text]
  • Developmental Changes in Calcium Channel Types Mediating Central Synaptic Transmission
    The Journal of Neuroscience, January 1, 2000, 20(1):59–65 Developmental Changes in Calcium Channel Types Mediating Central Synaptic Transmission Shinichi Iwasaki,1 Akiko Momiyama,2 Osvaldo D. Uchitel,3 and Tomoyuki Takahashi1 1Department of Neurophysiology, University of Tokyo Faculty of Medicine, Tokyo 113-0033, Japan, 2Laboratory of Cerebral Structure, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan, and 3Departamento de Ciencias Biologicas, Laboratorio de Fisiologia y Biologia, Molecular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires 1428, Argentina Multiple types of high-voltage-activated Ca 21 channels trigger fact, Ca 21 currents directly recorded from the auditory calyceal neurotransmitter release at the mammalian central synapse. presynaptic terminal were identified as N-, P/Q-, and R-types at Among them, the v-conotoxin GVIA-sensitive N-type channels postnatal day 7 (P7) to P10 but became predominantly P/Q- and the v-Aga-IVA-sensitive P/Q-type channels mediate fast type at P13. In contrast to thalamic and cerebellar IPSCs and synaptic transmission. However, at most central synapses, it is brainstem auditory EPSCs, N-type Ca 21 channels persistently not known whether the contributions of different Ca 21 channel contribute to cerebral cortical EPSCs and spinal IPSCs types to synaptic transmission remain stable throughout post- throughout postnatal months. Thus, in adult animals, synaptic natal development. We have addressed this question by testing transmission is predominantly mediated by P/Q-type channels type-specific Ca 21 channel blockers at developing central syn- at a subset of synapses and mediated synergistically by multi- apses.
    [Show full text]
  • GABA Enhances Transmission at an Excitatory Glutamatergic Synapse
    The Journal of Neuroscience, August 15, 2001, 21(16):5935–5943 GABA Enhances Transmission at an Excitatory Glutamatergic Synapse Scott Gutovitz, John T. Birmingham, Jason A. Luther, David J. Simon, and Eve Marder Volen Center and Biology Department, Brandeis University, Waltham, Massachusetts 02454-9110 GABA mediates both presynaptic and postsynaptic inhibition at ␤-(Aminomethyl)-4-chlorobenzenepropanoic acid (baclofen) many synapses. In contrast, we show that GABA enhances was an effective agonist for the GABA-evoked enhancement transmission at excitatory synapses between the lateral gastric but did not increase the postjunctional conductance. Muscimol and medial gastric motor neurons and the gastric mill 6a and 9 activated a rapid postsynaptic conductance but did not en- (gm6a, gm9) muscles and between the lateral pyloric motor hance the amplitude of the nerve-evoked EJPs. GABA had no neuron and pyloric 1 (p1) muscles in the stomach of the lobster effect on iontophoretic responses to glutamate and decreased Homarus americanus. Two-electrode current-clamp or voltage- the coefficient of variation of nerve-evoked EJPs. In the pres- clamp techniques were used to record from muscle fibers. The ence or absence of tetrodotoxin, GABA increased the fre- innervating nerves were stimulated to evoke excitatory junc- quency but not the amplitude of miniature endplate potentials. tional potentials (EJPs) or excitatory junctional currents. Bath These data suggest that GABA acts presynaptically via a application of GABA first decreased the amplitude of evoked GABAB-like receptor to increase the release of EJPs in gm6a and gm9 muscles, but not the p1 muscle, by neurotransmitter. activating a postjunctional conductance increase that was blocked by picrotoxin.
    [Show full text]
  • Presynaptic Establishment of the Synaptic Cleft Extracellular Matrix Is Required for Post-Synaptic Differentiation
    Downloaded from genesdev.cshlp.org on September 27, 2021 - Published by Cold Spring Harbor Laboratory Press Presynaptic establishment of the synaptic cleft extracellular matrix is required for post-synaptic differentiation Jeffrey Rohrbough, Emma Rushton, Elvin Woodruff III, Tim Fergestad, Krishanthan Vigneswaran, and Kendal Broadie1 Department of Biological Sciences, Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37235, USA Formation and regulation of excitatory glutamatergic synapses is essential for shaping neural circuits throughout development. In a Drosophila genetic screen for synaptogenesis mutants, we identified mind the gap (mtg), which encodes a secreted, extracellular N-glycosaminoglycan-binding protein. MTG is expressed neuronally and detected in the synaptic cleft, and is required to form the specialized transsynaptic matrix that links the presynaptic active zone with the post-synaptic glutamate receptor (GluR) domain. Null mtg embryonic mutant synapses exhibit greatly reduced GluR function, and a corresponding loss of localized GluR domains. All known post-synaptic signaling/scaffold proteins functioning upstream of GluR localization are also grossly reduced or mislocalized in mtg mutants, including the dPix–dPak–Dock cascade and the Dlg/PSD-95 scaffold. Ubiquitous or neuronally targeted mtg RNA interference (RNAi) similarly reduce post-synaptic assembly, whereas post-synaptically targeted RNAi has no effect, indicating that presynaptic MTG induces and maintains the post-synaptic pathways driving GluR domain formation. These findings suggest that MTG is secreted from the presynaptic terminal to shape the extracellular synaptic cleft domain, and that the cleft domain functions to mediate transsynaptic signals required for post-synaptic development. [Keywords: Glutamatergic synaptogenesis; post-synaptic density; glutamate receptor; secretion; Drosophila; neuromuscular junction] Supplemental material is available at http://www.genesdev.org.
    [Show full text]
  • Slitrk2 Controls Excitatory Synapse Development Via PDZ-Mediated
    www.nature.com/scientificreports OPEN Slitrk2 controls excitatory synapse development via PDZ-mediated protein interactions Kyung Ah Han 1,2, Jinhu Kim1,2, Hyeonho Kim1,2, Dongwook Kim1, Dongseok Lim1, Jaewon Ko 1 & Ji Won Um 1* Members of the Slitrk (Slit- and Trk-like protein) family of synaptic cell-adhesion molecules control excitatory and inhibitory synapse development through isoform-dependent extracellular interactions with leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs). However, how Slitrks participate in activation of intracellular signaling pathways in postsynaptic neurons remains largely unknown. Here we report that, among the six members of the Slitrk family, only Slitrk2 directly interacts with the PDZ domain-containing excitatory scafolds, PSD-95 and Shank3. The interaction of Slitrk2 with PDZ proteins is mediated by the cytoplasmic COOH-terminal PDZ domain-binding motif (Ile-Ser-Glu-Leu), which is not found in other Slitrks. Mapping analyses further revealed that a single PDZ domain of Shank3 is responsible for binding to Slitrk2. Slitrk2 forms in vivo complexes with membrane-associated guanylate kinase (MAGUK) family proteins in addition to PSD-95 and Shank3. Intriguingly, in addition to its role in synaptic targeting in cultured hippocampal neurons, the PDZ domain-binding motif of Slitrk2 is required for Slitrk2 promotion of excitatory synapse formation, transmission, and spine development in the CA1 hippocampal region. Collectively, our data suggest a new molecular mechanism for conferring isoform-specifc regulatory actions of the Slitrk family in orchestrating intracellular signal transduction pathways in postsynaptic neurons. Synapses are asymmetric intercellular junctions that permit transmission of signals from presynaptic to postsyn- aptic neurons.
    [Show full text]
  • Glial Contribution to Excitatory and Inhibitory Synapse Loss in Neurodegeneration Henstridge, Christopher; Tzioras, Makis; Paolicelli, Rosa Chiara
    University of Dundee Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration Henstridge, Christopher; Tzioras, Makis; Paolicelli, Rosa Chiara Published in: Frontiers in Cellular Neuroscience DOI: 10.3389/fncel.2019.00063 Publication date: 2019 Licence: CC BY Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Henstridge, C., Tzioras, M., & Paolicelli, R. C. (2019). Glial contribution to excitatory and inhibitory synapse loss in neurodegeneration. Frontiers in Cellular Neuroscience, 13, [63]. https://doi.org/10.3389/fncel.2019.00063 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 30. Sep. 2021 REVIEW published: 26 February 2019 doi: 10.3389/fncel.2019.00063
    [Show full text]
  • Final Copy 2019 01 23 Gurun
    This electronic thesis or dissertation has been downloaded from Explore Bristol Research, http://research-information.bristol.ac.uk Author: Gurung, Sonam Title: Kainate Receptors in various forms of plasticity General rights Access to the thesis is subject to the Creative Commons Attribution - NonCommercial-No Derivatives 4.0 International Public License. A copy of this may be found at https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode This license sets out your rights and the restrictions that apply to your access to the thesis so it is important you read this before proceeding. Take down policy Some pages of this thesis may have been removed for copyright restrictions prior to having it been deposited in Explore Bristol Research. However, if you have discovered material within the thesis that you consider to be unlawful e.g. breaches of copyright (either yours or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please contact [email protected] and include the following information in your message: •Your contact details •Bibliographic details for the item, including a URL •An outline nature of the complaint Your claim will be investigated and, where appropriate, the item in question will be removed from public view as soon as possible. Kainate Receptors in various forms of plasticity Sonam Gurung August 2018 A dissertation submitted to the University of Bristol in accordance with the requirements for award of the degree of Doctor of Philosophy by advanced study in the School of Biochemistry, Faculty of Life Sciences.
    [Show full text]
  • Redistribution and Stabilization of Cell Surface Glutamate Receptors During Synapse Formation
    The Journal of Neuroscience, October 1, 1997, 17(19):7351–7358 Redistribution and Stabilization of Cell Surface Glutamate Receptors during Synapse Formation Andrew L. Mammen,1,2 Richard L. Huganir,1,2 and Richard J. O’Brien1,2,3 1Howard Hughes Medical Institute, and Departments of 2Neuroscience and 3Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Although the regulation of neurotransmitter receptors during addition of N-GluR1 to live neurons. As cultures mature and synaptogenesis has been studied extensively at the neuromus- synapses form, there is a redistribution of surface GluR1 into cular junction, little is known about the control of excitatory clusters at excitatory synapses where it appears to be immo- neurotransmitter receptors during synapse formation in central bilized. The change in the distribution of GluR1 is accompanied neurons. Using antibodies against extracellular N-terminal (N- by an increase in both the half-life of the receptor and the GluR1) and intracellular C-terminal (C-GluR1) domains of the percentage of the total pool of GluR1 that is present on the cell AMPA receptor subunit GluR1, combined with surface biotiny- surface. Blockade of postsynaptic AMPA and NMDA receptors lation and metabolic labeling studies, we have characterized had no effect on the redistribution of GluR1. These results begin the redistribution and metabolic stabilization of the AMPA re- to characterize the events regulating the distribution of AMPA ceptor subunit GluR1 during synapse formation in culture. Be- receptors and demonstrate similarities between synapse for- fore synapse formation, GluR1 is distributed widely, both on the mation at the neuromuscular junction and at excitatory syn- surface and within the dendritic cytoplasm of these neurons.
    [Show full text]