DOCSLIB.ORG

Astroglial Glutamate Transporters in the Brain: Regulating Neurotransmitter Homeostasis and Synaptic Transmission

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Astroglial Glutamate Transporters in the Brain: Regulating Neurotransmitter Homeostasis and Synaptic Transmission Journal of Neuroscience Research 95:2140–2151 (2017) Review Astroglial Glutamate Transporters in the Brain: Regulating Neurotransmitter Homeostasis and Synaptic Transmission Ciaran Murphy-Royal,1,2 Julien Dupuis,2,3 Laurent Groc,2,3 and Stephane H. R. Oliet 1,2 1Neurocentre Magendie, Inserm U1215, Bordeaux, France 2Universite de Bordeaux, Bordeaux, France 3Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, Bordeaux, France Astrocytes, the major glial cell type in the central nervous compartments. As an example, the extracellular glutamate system (CNS), are critical for brain function and have concentration is maintained at low values lying most like- been implicated in various disorders of the central ner- ly below 100 nM (Hamberger and Nystrom,€ 1984; vous system. These cells are involved in a wide range of Cavelier and Attwell, 2005; Herman and Jahr, 2007), cerebral processes including brain metabolism, control of while it is much more concentrated inside cells. As there central blood flow, ionic homeostasis, fine-tuning synap- are no extracellular enzymes degrading glutamate, this tic transmission, and neurotransmitter clearance. Such low extracellular concentration can be fully accounted for varied roles can be efficiently carried out due to the inti- by specific transporters, which are widely expressed mate interactions astrocytes maintain with neurons, the throughout the brain (Furuta et al., 1997). Glutamate vasculature, as well as with other glial cells. Arguably, one transporters working under physiological conditions have of the most important functions of astrocytes in the brain the capacity to establish concentration gradients of 106 is their control of neurotransmitter clearance. This is across the plasma membrane, theoretically resulting in a particularly true for glutamate whose timecourse in the glutamate concentration of 10 nM extracellularly and 10 synaptic cleft needs to be controlled tightly under physio- mM intracellularly (Zerangue and Kavanaugh, 1996a). logical conditions to maintain point-to-point excitatory They also allow the maintenance of gradients with subcel- transmission, thereby limiting spillover and activation lular compartments, as in synaptic vesicles where gluta- of more receptors. Most importantly, accumulation of mate has been estimated to be present at concentrations glutamate in the extracellular space can trigger excessive up to 60 mM due to highly efficient vesicular glutamate activation of glutamatergic receptors and lead to transporters (Burger et al., 1989; Shupliakov et al., 1992; excitotoxicity, a trademark of many neurodegenerative diseases. It is thus of utmost importance for both physio- for review see El Mestikawy et al., 2011). In this review, logical and pathophysiological reasons to understand the processes that control glutamate time course within the SIGNIFICANCE synaptic cleft and regulate its concentrations in the extra- This review is aimed at summarizing our present knowledge on astro- cellular space. VC 2017 Wiley Periodicals, Inc. cytes and their role in glutamate clearance. Astrocytes are non-neuronal Key words: GLT-1; Astrocytes; surface trafficking; gluta- cell present in our brain where they ensure several key fonctions. One mate uptake of the most important role played by these glial cells is to clear the neu- rotransmitter glutamate from the extracellular space. This is essential to maintain an appropriate cerebral communication. Such clearance is made possible by highly-selective transporters that are expressed on INTRODUCTION astrocytes and which are endowed with specific properties and expres- Since the initial discovery of its excitatory action on sion profile. They could represent a target of choice for therapuetic neurons (Hayashi, 1954; Curtis and Watkins, 1960), glu- strategies in the context of neurodegenerative diseases. tamate has been found to be highly concentrated in the central nervous system of mammals, with estimates in the range of 5-15 mmol/kg (Danbolt, 2001). Yet this neuro- Received 13 October 2016; Revised 20 December 2016; Accepted 2 transmitter is not uniformly distributed. Indeed, vast dif- January 2017 ferences in glutamate concentrations of have been Published online 2 February 2017 in Wiley Online Library reported in extracellular, intracellular and subcellular (wileyonlinelibrary.com). DOI: 10.1002/jnr.24029 VC 2017 Wiley Periodicals, Inc. Astroglial Glutamate Uptake 2141 we discuss how these unique properties allow glutamate be differences between subtypes (Haugeto et al., 1996; transporters to fulfil critical functions such as ensuring the Yernool et al., 2003, 2004). All five EAATs transport kinetics and specificity of synaptic transmissions or pre- L-glutamate (and DL-aspartate) with high affinities venting neurotoxicity associated with excessive activation (30 lM for GLT-1; Arriza et al., 1994, 1997; Fairman of glutamate receptors (Tzingounis and Wadiche, 2007). et al., 1995), using energy stored in the concentration gra- dients of sodium and potassium. During one individual Distribution and Functional Properties of transport cycle, each transporter binds one extracellular Glutamate Transporters molecule of glutamate as well as three sodium ions and The family of brain glutamate transporters is com- one proton. The transporter then undergoes a conforma- posed of five members – namely excitatory amino acid tional change towards an inward facing conformation transporters 1 to 5 (EAAT1-5)—which have been exten- where these substrates are released into the cytoplasm. sively reviewed elsewhere (Danbolt, 2001). EAAT1 This step is followed by the binding of one internal potas- (GLAST) and EAAT2 (GLT-1) are ubiquitously sium ion and a switch back to an outward facing state, expressed in the brain, with GLT-1 being particularly completing the transport cycle (Zerangue and Kavanaugh, abundant in the hippocampus and the cortex whereas 1996a; Reyes et al., 2009). To note, EAAT3 also trans- GLAST is highly concentrated in the cerebellum (Roth- ports cysteine (Zerangue and Kavanaugh, 1996b). More- stein et al., 1994; Lehre et al., 1995; Chaudhry et al., over, uncoupled fluxes can occur and EAATs can 1995; Schmitt et al., 1997; Furuta et al., 1997). EAAT3 function as chloride channels, particularly EAAT4 and (EAAC1) is also ubiquitous in the central nervous system EAAT5 which display considerable chloride conductance and is particularly concentrated in the hippocampus and may thus be alternatively envisioned as inhibitory glu- where it is targeted to somatic and dendritic locations on tamate receptors (Dehnes et al., 1998; Veruki et al., 2006). neurons (Rothstein et al., 1994; Shashidharan et al., 1997; Holmseth et al., 2012). To note, EAAT3 is also expressed Importance of Glutamate Transporters: Lessons on GABAergic nerve terminals where it provides gluta- From Knock-Out Models and Human Mutations mate as a precursor for GABA synthesis (Sepkuty et al., It was not until the 1990’s that the different gluta- 2002; Mathews and Diamond, 2003; Stafford et al., mate transporters were identified and cloned (Storck 2010). EAAT4 expression is essentially found in the cere- et al., 1992; Kanai and Hediger, 1992; Pines et al., 1992; bellum on the dendrites of Purkinje cells (Fairman et al., Arriza et al., 1994, 1997; Fairman et al., 1995), which 1995; Dehnes et al., 1998). Finally, EAAT5 is very weak- eventually led to the generation of subtype-specific gluta- ly expressed in the central nervous system and is preferen- mate transporter knockout mice. Overwhelming evi- tially found in the retina (Arriza et al., 1997; Barnett and dence from glutamate transporter knockout models Pow, 2000; Lee et al., 2012). demonstrated that glial glutamate transporters are critical The EAAT family can be roughly divided based on for normal brain function (see Table I). Indeed, impaired cell-specific expression patterns, with EAAT1 (GLAST) GLT-1 activity causes a massive increase in extracellular and EAAT2 (GLT-1) mainly located on astrocytes while glutamate levels in GLT-1 knockouts (Tanaka et al., EAAT3-5 are exclusively neuronal. However, it is impor- 1997; Mitani and Tanaka, 2003; Takasaki et al., 2008). tant to note that there is evidence supporting GLT-1 While mice appear to be normal at birth, they show low- expression on cortical and hippocampal neurons, either er body weight and start to suffer from hyperactivity as from in situ hybridization or immunodetection well as severe epileptic seizures after two to three weeks, approaches ex vivo and in cultured neurons (Schmitt a time-window when synaptic clearing of neurotransmit- et al., 1996; Wang et al., 1998; Mennerick et al., 1998; ters shifts from passive diffusion to uptake by transporters Melone et al., 2009). In the hippocampal CA1 area for (Ullensvang et al., 1997; Furuta et al., 1997; Thomas example, glutamatergic axon terminals from CA3 pyrami- et al., 2011). About half of GLT-1-deficient animals die dal cells express functional GLT-1 with full glutamate within the first month of life (Tanaka et al., 1997; Matsu- transport ability which are believed to represent 5-10% of gami et al., 2006). Interestingly, cell-specific knock-outs total hippocampal GLT-1 (Chen et al., 2004; Berger models recently allowed to distinguish the relative impor- et al., 2005; Furness et al., 2008). While neuronal GLT-1 tance of astrocytic versus neuronal GLT-1 (Petr et al., allow noticeable glutamate uptake within hippocampal 2015) and confirmed that deletion of astrocytic GLT-1 nerve terminals, evidence is still lacking on whether
Load more

Recommended publications
  • Ultrastructural Study of the Granule Cell Domain of the Cochlear Nucleus in Rats: Mossy Fiber Endings and Their Targets
    THE JOURNAL OF COMPARATIVE NEUROLOGY 369~345-360 ( 1996) Ultrastructural Study of the Granule Cell Domain of the Cochlear Nucleus in Rats: Mossy Fiber Endings and Their Targets DIANA L. WEEDMAN, TAN PONGSTAPORN, AND DAVID K. RYUGO Center for Hearing Sciences, Departments of Otolaryngoloby-Head and Neck Surgery and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 2 1205 ABSTRACT The principal projection neurons of the cochlear nucleus receive the bulk of their input from the auditory nerve. These projection neurons reside in the core of the nucleus and are surrounded by an external shell, which is called the granule cell domain. Interneurons of the cochlear granule cell domain are the target for nonprimary auditory inputs, including projections from the superior olivary complex, inferior colliculus, and auditory cortex. The granule cell domain also receives projections from the cuneate and trigeminal nuclei, which are first-order nuclei of the somatosensory system. The cellular targets of the nonprimary projections are mostly unknown due to a lack of information regarding postsynaptic profiles in the granule cell areas. In the present paper, we examined the synaptic relationships between a heterogeneous class of large synaptic terminals called mossy fibers and their targets within subdivisions of the granule cell domain known as the lamina and superficial layer. By using light and electron microscopic methods in these subdivisions, we provide evidence for three different neuron classes that receive input from the mossy fibers: granule cells, unipolar brush cells, and a previously undescribed class called chestnut cells. The distinct synaptic relations between mossy fibers and members of each neuron class further imply fundamentally separate roles for processing acoustic signals.
    [Show full text]
  • Granule Cell Synapses of Rat Cerebellum: Experimental Observations and Theoretical Predictions
    Articles in PresS. J Neurophysiol (October 5, 2005). doi:10.1152/jn.00696.2005 1 LTP regulates burst initiation and frequency at mossy fiber – granule cell synapses of rat cerebellum: experimental observations and theoretical predictions Thierry Nieus1,2, Elisabetta Sola1,4, Jonathan Mapelli1, Elena Saftenku3, Paola Rossi1, Egidio D’Angelo1,2,* 1 Dept. of Cellular-Molecular Physiological and Pharmacological Sciences (University of Pavia) and INFM, Via Forlanini 6, I-27100, Pavia, Italy. 2 Dept. of Functional and Evolutionary Biology (University of Parma), Parco Area delle Scienze 11a, I-34100, Parma, Italy. 3 Dept. of General Physiology of Nervous System, A.A. Bogomoletz Institute of Physiology Bogomoletz St., 4, 01024, Kiev-24, Ukraine 4 present address: Dept. of Biophysics, SISSA, via Beirut 4, I-34014, Trieste, Italy * To whom correspondence should be addressed at [email protected] Key-words. LTP, Synaptic plasticity, Presynaptic mechanisms, Cerebellum, Granule cells Running title. LTP and bursting in the cerebellum Acknowledgments. This work was supported by projects of the European Community (CEREBELLUM QLG3-CT-2001-02256 and SPIKEFORCE IST-2001-35271), of MIUR and INFM of Italy to ED. ABSTRACT Long-term potentiation (LTP) is a synaptic change supposed to provide the cellular basis for learning and memory in brain neuronal circuits. Although specific LTP expression mechanisms could be critical to determine the dynamics of repetitive neurotransmission, this important issue remained largely unexplored. In this paper we have performed whole-cell patch-clamp recordings of mossy fiber – granule cell LTP in acute rat cerebellar slices and investigated its computational implications with a mathematical model. During LTP, stimulation with short impulse trains at 100 Hz revealed earlier initiation of granule cell spike bursts and a smaller non-significant spike frequency increase.
    [Show full text]
  • Three-Dimensional Morphology of Cerebellar Protoplasmic Islands
    Scanning Microscopy Volume 5 Number 2 Article 16 2-16-1991 Three-Dimensional Morphology of Cerebellar Protoplasmic Islands and Proteoglycan Content of Mossy Fiber Glomerulus: A Scanning and Transmission Electron Microscope Study O. J. Castejón Universidad del Zulia, Venezuela H. V. Castejón Universidad del Zulia, Venezuela Follow this and additional works at: https://digitalcommons.usu.edu/microscopy Part of the Biology Commons Recommended Citation Castejón, O. J. and Castejón, H. V. (1991) "Three-Dimensional Morphology of Cerebellar Protoplasmic Islands and Proteoglycan Content of Mossy Fiber Glomerulus: A Scanning and Transmission Electron Microscope Study," Scanning Microscopy: Vol. 5 : No. 2 , Article 16. Available at: https://digitalcommons.usu.edu/microscopy/vol5/iss2/16 This Article is brought to you for free and open access by the Western Dairy Center at DigitalCommons@USU. It has been accepted for inclusion in Scanning Microscopy by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. Scanning Microscopy , Vol. 5, No . 2, 1991 (Pages 477-494) 0891 -7035/91$3.00+ .00 Scanning Microscopy International , Chicago (AMF O'Hare) , IL 60666 USA THREE-DI MENSIONAL MORPHOLOGYOF CEREBELLAR PROTOPLASMIC ISLANDS AND PROTEOGLYCANCO NTENT OF MOSSY FIBER GLOMERULUS: A SCANNING AND TRANSMISSION ELECTRON MICROSCOPE STUDY 0. J . Cas tejon and H. V. Castejon Institute de Investigac1ones Biologicas. Facultad de Medicina . Universidad de l Zulia. Apart ado 526, Mara ca ibo, Venezu ela (Received for publication May 2, 1990 , and in revised form February 16, 1991) Abstract Introduction The present rev , ew summarizes the outer and The cerebellar protoplasmatic islands and inner surface features of mossy f ib er glomeru li the cerebellar glomeruli were studied at light 1n vertebra te cerebellar granular la yer as seen microscope level by Denissenko ( 18771, Ramon y by conv en t i ona l scanning electron microscopy Cajal ( 1889, 19551, Retzius ( 1892a,b), Lugaro <SEMI and SEM fre eze -f ra cture method .
    [Show full text]
  • Svetla P. Pencheva, Emilyan A. Ivanov Summary ULTRASTRUCTURAL
    J Biomed Clin Res Volume 6 Number 1, 2013 DOI: 10.1515/jbcr-2015-0095 Original Article ULTRASTRUCTURAL STUDY OF THE SYNAPTIC GLOMERULI IN THE RAT'S COCHLEAR NUCLEUS Svetla P. Pencheva, Summary Emilyan A. Ivanov The granule cell domain of the cochlear nuclear complex Department of Anatomy, Histology, contains interneurons, which are the targets for Citology and Biology nonprimary auditory inputs from the superior olivary complex, inferior colliculus, auditory cortex, cuneate and Medical University – Pleven trigeminal nuclei of the somatosensory system. The Bulgaria cellular targets of the non-primary projections are unknown due to a lack of information regarding postsynaptic profiles in the granule cell areas. In the present paper, we examined the synaptic relationships between a heterogeneous class of large synaptic terminals, called mossy fibers and their targets within subdivisions of the granule cell domain. During the late stage of postnatal development, we observed heterogenous groups of complex synaptic glomeruli. Using electron microscopy, we provide evidence for ultrastructural features of dendrites that receive input from the mossy fibers. The distinct synaptic relations between mossy fibers and dendrites of microneurons further imply fundamentally separate roles in processing of acoustic signals. Key wards: cochlear nucleus, granule cell domain, synaptic glomerulus Introduction The granule cell domain of the cochlear nucleus Corresponding Autor: comprises up to seven different subdivisions [1]. Svetla P. Pencheva These subdivisions are found around the core of the Sector of Anatomy, Histology and ventral cochlear nucleus (VCN) and the dorsal Cytology cochlear nucleus ( DCN), including the superficial Medical University-Pleven layer of the VCN, the lamina dividing DCN from Pleven, 5800 Bulgaria VCN, the subpeduncular dorsal corner of the VCN, е-mail: [email protected] the dorsal strial corner of the DCN, and layer II of the DCN [2, 3].
    [Show full text]
  • Morphogenetic Plasticity of Neuronal Elements in Cerebellar Glomeruli During Deafferentation-Induced Synaptic Reorganization J6zsefhhmori, Robert L
    (C)Freund Publishing House Ltd., 1997 Morphogenetic Plasticity of Neuronal Elements in Cerebellar Glomeruli during Deafferentation-Induced Synaptic Reorganization J6zsefHhmori, Robert L. Jakab and J6zsefTakb.cs Department ofAnatomy, Laboratory ofNeurobiology, Semmelweis University, Medical School, Budapest, Hungary, H-1094; Section ofNeurobiology, Yale University School ofMedicine, New Haven, CT, USA SUMMARY represented only one-fifth of all synaptic junctions. The quantitative data of the Reorganization of the cerebellar glomerulus, reorganized cerebellar glomerulus demonstrate the main synaptic complex within the granule both a remarkable constancy and a plasticity of cell layer, was investigated using quantitative the excitatory granule cells and inhibitory Golgi morphological techniques. All afferents to the neurons building up this synaptic complex. cerebellar cortex, including mossy-fibers, were Constancy (the preservation of certain specific surgically destroyed by undercutting the structural features) is represented by an cerebellar vermis. Fifteen days after the eventually unchanged number of dendrites and operation, which resulted in the removal of the synaptic junctions within the deafferented main excitatory afferent to the glomerulus, a glomerulus. Such constancy was made possible, significant reorganization of the whole synaptic however, by the morphogenetic plasticity of complex was observed, whereas the structural both nerve-cell types to produce new, dendro- integrity of the glomerulus was remarkably well dendritic and axo-dendritic synapses to preserved. This was indicated by the compensate for the loss of mossy-fiber synapses. observation that the number of granule cell dendrites per glomerulus), as well as the (50 KEY number of dendritic digits (210 per WORDS glomerulus) bearing most of the 230 synaptic eerebellar cortex, deafferentation, synaptic junctions per glomerulus, did not change EM significantly after mossy-fiber degeneration.
    [Show full text]
  • Phagocytic Glia Are Obligatory Intermediates in Transmission Of
    RESEARCH ARTICLE Phagocytic glia are obligatory intermediates in transmission of mutant huntingtin aggregates across neuronal synapses Kirby M Donnelly1, Olivia R DeLorenzo2, Aprem DA Zaya1, Gabrielle E Pisano1, Wint M Thu1, Liqun Luo3,4, Ron R Kopito3, Margaret M Panning Pearce1,2* 1Department of Biological Sciences, University of the Sciences, Philadelphia, United States; 2Program in Neuroscience, University of the Sciences, Philadelphia, United States; 3Department of Biology, Stanford University, Stanford, United States; 4Howard Hughes Medical Institute, Stanford University, Stanford, United States Abstract Emerging evidence supports the hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell to cell through the brain in a manner akin to infectious prions. Here, we show that mutant huntingtin (mHtt) aggregates associated with Huntington disease transfer anterogradely from presynaptic to postsynaptic neurons in the adult Drosophila olfactory system. Trans-synaptic transmission of mHtt aggregates is inversely correlated with neuronal activity and blocked by inhibiting caspases in presynaptic neurons, implicating synaptic dysfunction and cell death in aggregate spreading. Remarkably, mHtt aggregate transmission across synapses requires the glial scavenger receptor Draper and involves a transient visit to the glial cytoplasm, indicating that phagocytic glia act as obligatory intermediates in aggregate spreading between synaptically-connected neurons. These findings expand our understanding
    [Show full text]
  • Calcium Dynamics in Astrocyte Processes During Neurovascular Coupling
    ART ic LE S Calcium dynamics in astrocyte processes during neurovascular coupling Yo Otsu1,2,7, Kiri Couchman1,2,7, Declan G Lyons1,2, Mayeul Collot3,4, Amit Agarwal5, Jean-Maurice Mallet3,4, Frank W Pfrieger6, Dwight E Bergles5 & Serge Charpak1,2 Enhanced neuronal activity in the brain triggers a local increase in blood flow, termed functional hyperemia, via several mechanisms, including calcium (Ca2+) signaling in astrocytes. However, recent in vivo studies have questioned the role of astrocytes in functional hyperemia because of the slow and sparse dynamics of their somatic Ca2+ signals and the absence of glutamate metabotropic receptor 5 in adults. Here, we reexamined their role in neurovascular coupling by selectively expressing a genetically encoded Ca2+ sensor in astrocytes of the olfactory bulb. We show that in anesthetized mice, the physiological activation of olfactory sensory neuron (OSN) terminals reliably triggers Ca2+ increases in astrocyte processes but not in somata. These Ca2+ increases systematically precede the onset of functional hyperemia by 1–2 s, reestablishing astrocytes as potential regulators of neurovascular coupling. Brain activity increases cerebral blood flow using a feed-forward are highly compartmentalized and that activity in discrete regions of mechanism that is independent of energy consumption. Enhanced their processes, termed microdomains, are often uncorrelated with release of glutamate from excitatory neurons is thought to induce events that occur in the soma. These results suggest that astrocyte vessel dilation through three potential signaling pathways (for reviews Ca2+ dynamics may be more heterogeneous and complex than previ- see refs. 1–3). The ‘neuron to arteriole’ hypothesis posits that a ously assumed17–19 and that activity in microdomains could be subject 2+ 2+ 20 glutamate-evoked rise in intracellular Ca concentration ([Ca ]i) to local independent modulation .
    [Show full text]
  • Pathway Specific Drive of Cerebellar Golgi Cells Reveals Integrative Rules of Cortical Inhibition
    bioRxiv preprint doi: https://doi.org/10.1101/356378; this version posted June 27, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Pathway specific drive of cerebellar Golgi cells reveals integrative rules of cortical inhibition Sawako Tabuchi1, Jesse I. Gilmer1,2, Karen Purba1, Abigail L. Person1 1. Department of Physiology & Biophysics 2. Neuroscience Graduate Program, University of Colorado Denver University of Colorado School of Medicine Aurora, CO 80045 Abstract: 222 words Significance Statement: 115 Introduction: 644 Discussion: 1,587 words Figures: 6 Tables: 0 Abbreviated title: Golgi cell structure-function relationship Address for Correspondence: Abigail L. Person, Ph.D. Department of Physiology & Biophysics University of Colorado School of Medicine 12800 East 19th Ave RC-1 North Campus Box 8307 Aurora, CO 80045 USA email: [email protected] (303) 724-4514 Conflict of Interest: The authors declare no competing financial interests. Acknowledgements: We thank Ms Samantha Lewis for expert technical support during the project. This work was supported by the Japan Society for The Promotion of Science (JSPS) Overseas Research Fellowship and The Uehara Memorial Foundation research fellowship to S.T.; NS084996 ; a Kingenstein Foundation fellowship; and a Boettcher foundation Webb-Waring biomedical research award to A.L.P. Imaging experiments were performed in the University of Colorado Anschutz Medical Campus Advance Light Microscopy Core supported in part by Rocky Mountain Neurological Disorders Core Grant Number P30NS048154 and by NIH/NCATS Colorado CTSI Grant Number UL1 TR001082. Engineering support was provided by the Optogenetics and Neural Engineering Core at the University of Colorado Anschutz Medical Campus, funded in part by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number P30NS048154.
    [Show full text]
  • Glossary.Pdf
    Glossary Pronunciation Key accessory fruit A fruit, or assemblage of fruits, adaptation Inherited characteristic of an organ- Pronounce in which the fleshy parts are derived largely or ism that enhances its survival and reproduc- a- as in ace entirely from tissues other than the ovary. tion in a specific environment. – Glossary Ј Ј a/ah ash acclimatization (uh-klı¯ -muh-tı¯-za -shun) adaptive immunity A vertebrate-specific Physiological adjustment to a change in an defense that is mediated by B lymphocytes ch chose environmental factor. (B cells) and T lymphocytes (T cells). It e¯ meet acetyl CoA Acetyl coenzyme A; the entry com- exhibits specificity, memory, and self-nonself e/eh bet pound for the citric acid cycle in cellular respi- recognition. Also called acquired immunity. g game ration, formed from a fragment of pyruvate adaptive radiation Period of evolutionary change ı¯ ice attached to a coenzyme. in which groups of organisms form many new i hit acetylcholine (asЈ-uh-til-ko–Ј-le¯n) One of the species whose adaptations allow them to fill dif- ks box most common neurotransmitters; functions by ferent ecological roles in their communities. kw quick binding to receptors and altering the perme- addition rule A rule of probability stating that ng song ability of the postsynaptic membrane to specific the probability of any one of two or more mu- o- robe ions, either depolarizing or hyperpolarizing the tually exclusive events occurring can be deter- membrane. mined by adding their individual probabilities. o ox acid A substance that increases the hydrogen ion adenosine triphosphate See ATP (adenosine oy boy concentration of a solution.
    [Show full text]
  • Molecular Pathways Mediating Glial Responses During Wallerian Degeneration: a Dissertation
    University of Massachusetts Medical School eScholarship@UMMS GSBS Dissertations and Theses Graduate School of Biomedical Sciences 2015-05-14 Molecular Pathways Mediating Glial Responses during Wallerian Degeneration: A Dissertation Tsai-Yi Lu University of Massachusetts Medical School Let us know how access to this document benefits ou.y Follow this and additional works at: https://escholarship.umassmed.edu/gsbs_diss Part of the Molecular and Cellular Neuroscience Commons Repository Citation Lu T. (2015). Molecular Pathways Mediating Glial Responses during Wallerian Degeneration: A Dissertation. GSBS Dissertations and Theses. https://doi.org/10.13028/M26W2Q. Retrieved from https://escholarship.umassmed.edu/gsbs_diss/779 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in GSBS Dissertations and Theses by an authorized administrator of eScholarship@UMMS. For more information, please contact [email protected]. MOLECULAR PATHWAYS MEDIATING GLIAL RESPONSES DURING WALLERIAN DEGENERATION A Dissertation Presented By Tsai-Yi Lu Submitted to the Faculty of the University of Massachusetts Graduate School of Biomedical Sciences, Worcester in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 14th, 2015 Interdisciplinary Graduate Program ii MOLECULAR PATHWAYS MEDIATING GLIAL RESPONSES DURING WALLERIAN DEGENERATION A Dissertation Presented By Tsai-Yi Lu The signatures of the Dissertation Defense Committee signify completion and approval as to style and content of the Dissertation
    [Show full text]
  • Mitral Cell Dendritic Development in the Mouse Main Olfactory Bulb Masha Rand Diede Yale University
    Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 2-11-2008 Mitral Cell Dendritic Development in the Mouse Main Olfactory Bulb Masha Rand Diede Yale University Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Recommended Citation Diede, Masha Rand, "Mitral Cell Dendritic Development in the Mouse Main Olfactory Bulb" (2008). Yale Medicine Thesis Digital Library. 320. http://elischolar.library.yale.edu/ymtdl/320 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. MITRAL CELL DENDRITIC DEVELOPMENT IN THE MOUSE MAIN OLFACTORY BULB A Thesis Submitted to the Yale University School of Medicine in Partial Fulfillment of the Requirements for the Degree of Doctor of Medicine by Masha Rand Diede 2007 ABSTRACT Mitral cell dendritic development in the mouse main olfactory bulb. Masha Rand Diede and Charles A. Greer. Department of Neurosurgery, Yale University, School of Medicine, New Haven, CT. Correct targeting and differentiation of the mitral cell (MC) dendrites in the olfactory bulb (OB) is clearly essential for development of functional neuronal circuits. MCs, the primary OB projection neurons, receive odor information from OSN axons via axodendritic synapses on their apical dendrite; the signal is further processed via dendrodendritic synapses on MC lateral dendrites.
    [Show full text]
  • An Energy Budget for the Olfactory Glomerulus
    9790 • The Journal of Neuroscience, September 5, 2007 • 27(36):9790–9800 Cellular/Molecular An Energy Budget for the Olfactory Glomerulus Janna C. Nawroth,1,3 Charles A. Greer,3 Wei R. Chen,3 Simon B. Laughlin,2 and Gordon M. Shepherd3 1Master Program Molecular Biotechnology, Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, D-69120 Heidelberg, Germany, 2Department of Zoology, Cambridge University, Cambridge CB2 3EJ, United Kingdom, and 3Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510 Energy demands are becoming recognized as an important constraint on neural signaling. The olfactory glomerulus provides a well defined system for analyzing this question. Odor stimulation elicits high-energy demands in olfactory glomeruli where olfactory axons converge onto dendrites of olfactory bulb neurons. We performed a quantitative analysis of the energy demands of each type of neuronal element within the glomerulus. This included the volumes of each element, their surface areas, and ion loads associated with membrane potentials and synaptic activation as constrained by experimental observations. In the resting state, there was a high-energy demand compared with other brain regions because of the high density of neural elements. The activated state was dominated by the energy demands of action potential propagation in afferent olfactory sensory neurons and their synaptic input to dendritic tufts, whereas subsequent dendritic potentials and dendrodendritic transmission contributed only a minor share of costs. It is proposed therefore that afferent input and axodendritic transmission account for the strong signals registered by 2-deoxyglucose and functional magnetic resonance imaging, although postsynaptic dendrites comprise at least one-half of the volume of the glomerulus.
    [Show full text]