DOCSLIB.ORG

Overview of Synaptic Transmission 179

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Overview of Synaptic Transmission 179 1010 OverviewOverview ofof SynapticSynaptic Tr,Transmission Syn.apsesAre Either Electrical or Chemical electrical or chemical. Moreover, the strength of both Electrical Syn.apsesProvide Instantaneous Signal forms of synaptic transmission can be enhanced or di- 1I:ansmission minished by cellular activity. This pblsticity in nerve cells Gap-JunctionChannels Connect Communicating Cells at is crucial to memory and other higher brain functions. an Electrical Synapse In the brain, electrical synaptic transmission is ElectricalTransmission Allows the Rapid and rapid and rather stereotyped. Electrical synapses are SynchronousFiring of InterconnectedCells used primarily to send simple depolarizing signals; Gap JunctionsHave a Role in Glial Function and Disease they do not lend themselves to producing inhibitory ac- tions or making long-lasting changes in the electrical Chemical SynapsesCan Amplify Signals properties of postsynaptic cells. In contrast, chemical Chemical TransmittersBind to PostsynapticReceptors synapses are capable of more variable signaling and PostsynapticReceptors Gate Ion ChannelsEither Directly thus can produce more complex behaviors.They can or Indirectly mediate either excitatory or inhibitory actions in post- synaptic cells and produce electrical changes in the postsynaptic cell that last from milliseconds to many minutes. Chemical synapsesalso serve to amplify neu- W HATGIVES NERVE CELLS their special ability to ronal signals,so that evena smallpresynaptic nerve ter- communicate with one another so rapidly, minal can alter the responseof a large postsynaptic cell. over such great distances, and with such Becausechemical synaptic transmission is so central to tremendous precision? We have already seen how sig- understanding brain and behavior, it is examined in de- nals are propagated within a neuron, from its dendrites tail in Chapters 11, 12, and 13. and cell body to its axonal terminal. Beginning with this chapter we consider the cellular mechanisms for signal- ing betweenneurons. The point at which one neuron Synapses Are Either Electrical or Chemical communicates with another is called a synapse,and synaptic transmission is fundamental to many of the The term synapsewas introduced at the turn of the cen- processeswe consider later in the book, such as percep- tury by Charles Sherrington to describe the specialized tion, voluntary movement, and learning. zone of contact at which one neuron communicateswith Theaverage neuron forms about 1000synaptic con- another; this site had first been described histologically nections and receives even more, perhaps as many as (at the level of light microscopy) by Ram6n y Cajal. Ini- 10,000connections. The Purkinje cell of the cerebellum tially, all synapseswere thought to operate by means of receivesup to 100,000inputs. Although many of these electrical transmission. In the 1920s, however, Otto connections are highly specialized, all neurons make Loewi showed that acetylcholine (ACh), a chemicalcom- use of one of two basic forms of synaptic transmission: pound, conveys signals from the vagus nerve to the 176 Partm / ElementaryInteractions Between Neurons: Synaptic Thansmission Table 10-1 Distinguishing Properties of Electrical and Chemical Synapses Distance between Cytoplasmic pre- and continuity Type of postsynaptic cell between pre- and Ultrastructural Agent of Synaptic Direction of synapse membranes postsynaptic cells components transmission delay transmission Electrical 3.5nm Yes Gap-junction Ion current Vtrtually Usually channels absent bidirectional Chemical 20-40nm No Presynaptic Chemical Significant: Unidirec- vesicles and transmitter at least 0.3 tional active zones; IDS,usually postsynaptic 1-5 IDS receptors or longer heart. Loewi's discovery in the heart provoked consid- When physiological techniques improved in the erable debate in the 193Osover how chemical signals 19508and 1960sit becameclear that both forms of trans- could generateelectrical activities at other synapses,in- mission exist. Although most synapsesuse a chemical cluding nerve-muscle synapses and synapses in the transmitter, some operate purely by electrical means. brain. Oncethe fine structure of synapses was made visible Two schools of thought emerged, one physiological with the electron microscope, chemical and electrical and the other pharmacological. Each championed a sin- synapseswere found to have different morphologies. At gle mechanism for all synaptic transmission. The physi- chemical synapsesneurons are separatedcompletely by ologists, led by John Eccles (Sherrington's student), ar- a small space, the synaptic cleft. There is no continuity gued that all synaptic transmission is electrical, that the between the cytoplasm of one cell and the next. In con- action potential in the presynaptic neuron generates a trast, at electrical synapses the pre- and postsynaptic current that flows passively into the postsynaptic cell. cells communicate through special channels, the gap- The pharmacologists, led by Henry Dale, argued that junction channels,that serve as conduits between the cy- transmission is chemical, that the action potential in the toplasm of the two cells. presynaptic neuron leads to the release of a chemical The main functional properties of the two types of substancethat in turn initiates current flow in the post- synapses are summarized in Table 10-1. The most im- synaptic cell. portant differences can be observed by injecting current A Current flow at electrical synapses B Current flow at chemical synapses I Presyneptjc Postsynaptic Figure10-1 Currentflows differently at electricaland chem- B. At chemical synapsesall of the injected current escapes ical synapses. through ion channels in the presynapticcell. However,the re- A. At an electrical synapse some of the current injected into a sulting depolarizationof the cell activates the releaseof neuro- presynapticcell escapes through resting ion channels in the transmitter molecules packagedin synaptic vesicles (open cir- cell membrane.However, some current also flows into the clesl, which then bind to receptors on the postsynapticcell. postsynapticcell through specializedion channels. called gap- This binding opens ion channels,thus initiating a change in junction channels,that connect the cytoplasm of the pre- and membrane potential in the postsynaptic cell. postsynapticcells. Chapter10 I Overviewof SynapticTransmission 177 I A Experimentalsetup Current PresYl18ptic neuron: Injection Ieter8I gie~ fiber Recordng---- Iecording Cutr8nt~ injection Figure 10-2 Electrical synaptic transmission was first voltage are placed within both the p(f~ and postsynapticcells. demonstrated to occur at the giant motor synapse in the B. Transmissionat an electrical synapse is virtually instant&- crayfish. (Adaptedfrom Furshpanand Potter 1957 and 1959.) neous-the postsynapticresponse follows presynapticstimula- A. The presynapticneuron is the lateral giant fiber running tion in a fraction of a millisecond.The dashed line shows how down the nerve cord. The postsynaptic neuron is the motor the responsesof the two cells correspond in time. In contrast. fiber.which projectsfrom the cell bodyin the ganglionto the at chemical synapsesthere ia a delay between the pre- and I periphery.The electrodes for passing current and for recording postsynaptic potentials (see Figure 1~7). j into the presynaptic cell to elicit a signal (Figure to-t). external membrane of the postsynaptic ceIL which has a 1 At both types of synapses the current flows outward high resistance(Figure 10-1B).Instead, the action poten- C acrossthe presynaptic cell membrane. This current de- tial in the presynaptic neuron initiates the release of a 1 posits a positive charge on the inside of the presynaptic chemical transmitter, which diffuses acrossthe synaptic c cell membrane, reducing its negative charge and cleft to interact with receptors on the membrane of the t thereby depolarizing the cell (seeChapter 8). postsynaptic cell. Receptor activation causesthe cell ei- At electrical synapses the gap-junction channels ther to depolarize or to hyperpolarize. t that connect the pre- and postsynaptic cells provide a 14 low-resistance (high conductance) pathway for electri- C cal current to flow between the two cells. Thus, some of Electrical Synapses Provide Instantaneous tJ the current injected in the presynaptic cell flows Signal Transmission tJ through these channels into the postsynaptic cell. This c current deposits a positive charge on the inside of the At electrical synapses the current that depoJarizesthe D membrane of the postsynaptic cell and depolarizes it. postsynaptic cell is generated directly by the voltage- T The current then flows out through resting ion channels gated ion channels of the presynaptic cell. Thus these it in the postsynaptic cell (Figure to-tA). H the depolariza- channels not only have to depolarize the presynaptic ti tion exceeds threshold, voltage-gated ion channels in cell above the threshold for an action potential, they t1 the postsynaptic cell will open and generate an action must also generate sufficient ionic current to produce a P potential. change in potential in the postsynaptic cell. To generate At chemical synapses there is no direct low-resis- such a large current, the presynaptic terminal has to be ta tance pathway between the pre- and postsynaptic cells. large enough for its membrane to contain a large num- T Thus, current injected into a presynaptic cell flows out ber of ion channels. At the same time, the postsynaptic 01 of the cell's resting
Load more

Recommended publications
  • Electrical Synapses Are Drivers of Neural Plasticity Through Passage of Small Molecules
    Electrical Synapses are Drivers of Neural Plasticity Through Passage of Small Molecules Lisa Voelker A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington 2019 Reading Committee: Jihong Bai, Chair Linda Buck Cecilia Moens Program Authorized to Offer Degree: Molecular and Cellular Biology ©Copyright 2019 Lisa Voelker 2 University of Washington Abstract Electrical Synapses are Drivers of Neural Plasticity through Passage of Small Molecules Lisa Voelker Chair of the Supervisory Committee: Jihong Bai Department of Biochemistry In order to respond to changing environments and fluctuations in internal states, animals adjust their behavior through diverse neuromodulatory mechanisms. In this study we show that electrical synapses between the ASH primary quinine-detecting sensory neurons and the neighboring ASK neurons are required for modulating the aversive response to the bitter tastant quinine in C. elegans. Mutant worms that lack the electrical synapse proteins INX-18 and INX-19 become hypersensitive to dilute quinine. Cell-specific rescue experiments indicate that inx-18 operates in ASK while inx-19 is required in both ASK and ASH for proper quinine sensitivity. Imaging analyses find that INX-19 in ASK and ASH localizes to the same regions in the nerve ring, suggesting that both sides of ASK-ASH electrical synapses contain INX-19. While inx-18 and inx-19 mutant animals have a similar behavioral phenotype, several lines of evidence suggest the proteins encoded by these genes play different roles in modulating the aversive quinine response. First, INX-18 and INX-19 localize 3 to different regions of the nerve ring, indicating that they are not present in the same synapses.
    [Show full text]
  • Nervous Tissue
    Nervous Tissue Prof.Prof. ZhouZhou LiLi Dept.Dept. ofof HistologyHistology andand EmbryologyEmbryology Organization:Organization: neuronsneurons (nerve(nerve cells)cells) neuroglialneuroglial cellscells Function:Function: Ⅰ Neurons 1.1. structurestructure ofof neuronneuron somasoma neuriteneurite a.a. dendritedendrite b.b. axonaxon 1.11.1 somasoma (1)(1) nucleusnucleus LocatedLocated inin thethe centercenter ofof soma,soma, largelarge andand palepale--stainingstaining nucleusnucleus ProminentProminent nucleolusnucleolus (2)(2) cytoplasmcytoplasm (perikaryon)(perikaryon) a.a. NisslNissl bodybody b.b. neurofibrilneurofibril NisslNissl’’ss bodiesbodies LM:LM: basophilicbasophilic massmass oror granulesgranules Nissl’s Body (TEM) EMEM:: RERRER,, freefree RbRb FunctionFunction:: producingproducing thethe proteinprotein ofof neuronneuron structurestructure andand enzymeenzyme producingproducing thethe neurotransmitterneurotransmitter NeurofibrilNeurofibril thethe structurestructure LM:LM: EM:EM: NeurofilamentNeurofilament micmicrotubulerotubule FunctionFunction cytoskeleton,cytoskeleton, toto participateparticipate inin substancesubstance transporttransport LipofuscinLipofuscin (3)(3) CellCell membranemembrane excitableexcitable membranemembrane ,, receivingreceiving stimutation,stimutation, fromingfroming andand conductingconducting nervenerve impulesimpules neurite: 1.2 Dendrite dendritic spine spine apparatus Function: 1.3 Axon axon hillock, axon terminal, axolemma Axoplasm: microfilament, microtubules, neurofilament, mitochondria,
    [Show full text]
  • 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.
    [Show full text]
  • 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).
    [Show full text]
  • 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).
    [Show full text]
  • 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.
    [Show full text]
  • 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 ............................................................................
    [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]
  • 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]
  • Electrical Synaptic Transmission Requires a Postsynaptic Scaffolding Protein
    bioRxiv preprint doi: https://doi.org/10.1101/2020.12.03.410696; this version posted December 4, 2020. 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 4.0 International license. TITLE: Electrical synaptic transmission requires a postsynaptic scaffolding protein Abagael M. Lasseigne1*, Fabio A. Echeverry2*, Sundas Ijaz2*, Jennifer Carlisle Michel1*, E. Anne Martin1, Audrey J. Marsh1, Elisa Trujillo1, Kurt C. Marsden3, Alberto E. Pereda2#, Adam C. Miller1#@ * denotes co-first author # denotes co-corresponding author @ denotes lead contact Affiliations: 1 Institute of Neuroscience, University of Oregon, Eugene, OR 97403, USA 2 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA 3 Department of Biological Sciences, NC State University, Raleigh, NC 27695, USA Correspondence: [email protected] [email protected] Keywords: gap junction; connexin; ZO1 ZO-1; synaptic development; electrical coupling 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.03.410696; this version posted December 4, 2020. 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 4.0 International license. SUMMARY Electrical synaptic transmission relies on neuronal gap junctions containing channels constructed by Connexins. While at chemical synapses neurotransmitter-gated ion channels are critically supported by scaffolding proteins, it is unknown if channels at electrical synapses require similar scaffold support.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]