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Developmental pattern of three vesicular glutamate transporters in the rat superior olivary complex

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Abstract

Vesicular glutamate transporters (VGLUTs) mediate the packaging of the excitatory neurotransmitter glutamate into synaptic vesicles. Three VGLUT subtypes have been identified so far, which are differentially expressed in the brain. Here, we have investigated the spatiotemporal distribution of the three VGLUTs in the rat superior olivary complex (SOC), a prominent processing center, which receives strong glutamatergic inputs and which lies within the auditory brainstem. Immunoreactivity (ir) against all three VGLUTs was found in the SOC nuclei throughout development (postnatal days P0–P60). It was predominantly seen in axon terminals, although cytoplasmic labeling also occurred. Each transporter displayed a characteristic expression pattern. In the adult SOC, VGLUT1 labeling varied from strong in the medial nucleus of the trapezoid body, lateral superior olive, and medial superior olive (MSO) to moderate (ventral and lateral nuclei of the trapezoid body) to faint (superior paraolivary nucleus). VGLUT2-ir was moderate to strong throughout the SOC, whereas VGLUT3 was only weakly expressed. These results extend previous reports on co-localization of VGLUTs in the auditory brainstem. As in the adult, specific features were seen during development for all three transporters. Intensity increases and decreases occurred with both VGLUT1 and VGLUT3, whereas VGLUT2-ir remained moderately high throughout development. A striking result was obtained with VGLUT3, which was only transiently expressed in the different SOC nuclei between P0 and P12. A transient occurrence of VGLUT1-immunoreactive terminals on somata of MSO neurons was another striking finding. Our results imply a considerable amount of synaptic reorganization in the glutamatergic inputs to the SOC and suggest differential roles of VGLUTs during maturation and in adulthood.

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References

  • Aihara Y, Mashima H, Onda H, Hisano S, Kasuya H, Hori T, Yamada S, Tomura H, Yamada Y, Inoue I, Kojima I, Takeda J (2000) Molecular cloning of a novel brain-type Na+-dependent inorganic phosphate cotransporter. J Neurochem 74:2622–2625

    Google Scholar 

  • Behrend O, Brand A, Kapfer C, Grothe B (2002) Auditory response properties in the superior paraolivary nucleus of the gerbil. J Neurophysiol 87:2915–2928

    Google Scholar 

  • Bellocchio EE, Reimer RJ, Fremeau RT, Edwards RH (2000) Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter. Science 289:957–960

    Google Scholar 

  • Brew HM, Forsythe ID (1995) Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse. J Neurosci 15:8011–8022

    Google Scholar 

  • Caicedo A, Eybalin M (1999) Glutamate receptor phenotypes in the auditory brainstem and mid-brain of the developing rat. Eur J Neurosci 11:51–74

    Google Scholar 

  • Caspary DM, Finlayson PG (1991) Superior olivary complex: functional neuropharmacology of the principal cell types. In: Altschuler RA, Bobbin RP, Clopton BM, Hoffman DW (eds) Neurobiology of hearing: the central auditory system. Raven, New York, pp 141–161

    Google Scholar 

  • Dehmel S, Kopp-Scheinpflug C, Dörrscheidt GJ, Rübsamen R (2002) Electrophysiological characterization of the superior paraolivary nucleus in the Mongolian gerbil. Hearing Res 172:18–36

    Google Scholar 

  • Dingledine R, Borges K, Bowie D, Traynelis SF (1999) The glutamate receptor ion channels. Pharmacol Rev 51:7–61

    CAS  PubMed  Google Scholar 

  • Dodson PD, Forsythe ID (2004) Presynaptic K+ channels: electrifying regulators of synaptic terminal excitability. Trends Neurosci 27:210–217

    Google Scholar 

  • Forsythe ID (1994) Direct patch recording from identified presynaptic terminals mediating glutamatergic EPSCs in the rat CNS, in vitro. J Physiol (Lond) 479:381–387

    Google Scholar 

  • Fremeau RT, Troyer MD, Pahner I, Nygaard GO, Tran CH, Reimer RJ, Bellocchio EE, Fortin D, Storm-Mathisen J, Edwards RH (2001) The expression of vesicular glutamate transporters defines two classes of excitatory synapse. Neuron 31:247–260

    Google Scholar 

  • Fremeau RT, Burman J, Qureshi T, Tran CH, Proctor J, Johnson J, Zhang H, Sulzer D, Copenhagen DR, Storm-Mathisen J, Reimer RJ, Chaudhry FA, Edwards RH (2002) The identification of vesicular glutamate transporter 3 suggests novel modes of signaling by glutamate. Proc Natl Acad Sci USA 99:14488–14493

    Google Scholar 

  • Fremeau RT, Kam K, Qureshi T, Johnson J, Copenhagen DR, Storm-Mathisen J, Chaudhry FA, Nicoll RA, Edwards RH (2004a) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304:1815–1819

    Google Scholar 

  • Fremeau RT, Voglmaier S, Seal RP, Edwards RH (2004b) VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci 27:98–103

    Google Scholar 

  • Friauf E, Ostwald J (1988) Divergent projections of physiologically characterized rat ventral cochlear nucleus neurons as shown by intraaxonal injection of horseradish peroxidase. Exp Brain Res 73:263–284

    Google Scholar 

  • Friauf E, Aragón C, Löhrke S, Westenfelder B, Zafra F (1999) Developmental expression of the glycine transporter GLYT2 in the auditory system of rats suggests involvement in synapse maturation. J Comp Neurol 412:17–37

    Google Scholar 

  • Fyk-Kolodziej B, Dzhagaryan A, Qin P, Pourcho RG (2004) Immunocytochemical localization of three vesicular glutamate transporters in the cat retina. J Comp Neurol 475:518–530

    Google Scholar 

  • Geal-Dor M, Freeman S, Li G, Sohmer H (1993) Development of hearing in neonatal rats: air and bone conducted ABR thresholds. Hearing Res 69:236–242

    Google Scholar 

  • Gersdorff H von, Borst JGG (2002) Short-term plasticity at the calyx of Held. Nat Rev Neurosci 3:53–64

    Google Scholar 

  • Gersdorff H von, Schneggenburger R, Weis S, Neher E (1997) Presynaptic depression at a calyx synapse: the small contribution of metabotropic glutamate receptors. J Neurosci 17:8137–8146

    PubMed  Google Scholar 

  • Glendenning KK, Baker BN, Hutson KA, Masterton RB (1992) Acoustic chiasm V: inhibition and excitation in the ipsilateral and contralateral projections of LSO. J Comp Neurol 319:100–122

    Google Scholar 

  • Grandes P, Streit P (1997) Glutamate-like immunoreactivity in calyces of Held. J Neurocytol 18:685–693

    Google Scholar 

  • Gras C, Herzog E, Bellenchi GC, Bernard V, Ravassard P, Pohl M, Gasnier B, Giros B, El Mestikawy S (2002) A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons. J Neurosci 22:5442–5451

    Google Scholar 

  • Härtig W, Riedel A, Grosche J, Edwards RH, Fremeau RT, Harkany T, Brauer K, Arendt T (2003) Complementary distribution of vesicular glutamate transporters 1 and 2 in the nucleus accumbens of rat: relationship to calretinin-containing extrinsic innervation and calbindin-immunoreactive neurons. J Comp Neurol 465:1–10

    Google Scholar 

  • Haverkamp S, Wässle H (2004) Characterization of an amacrine cell type of the mammalian retina immunoreactive for vesicular glutamate transporter 3. J Comp Neurol 468:251–263

    Google Scholar 

  • Helfert RH, Bonneau JM, Wenthold RJ, Altschuler RA (1989) GABA and glycine immunoreactivity in the guinea pig superior olivary complex. Brain Res 501:269–286

    Google Scholar 

  • Helfert RH, Snead CR, Altschuler RA (1991) The ascending auditory pathways. In: Altschuler RA (ed) Neurobiology of hearing: the central auditory system. Raven, New York, pp 1–25

    Google Scholar 

  • Herzog E, Bellenchi GC, Gras C, Bernard V, Ravassard P, Bedet C, Gasnier B, Giros B, El Mestikawy S (2001) The existence of a second vesicular glutamate transporter specifies subpopulations of glutamatergic neurons. J Neurosci 21:RC181

    Google Scholar 

  • Herzog E, Gilchrist J, Gras C, Muzerelle A, Ravassard P, Giros B, Gaspar P, El Mestikawy S (2004) Localization of VGLUT3, the vesicular glutamate transporter type 3, in the rat brain. Neuroscience 123:983–1002

    Google Scholar 

  • Hisano S (2003) Vesicular glutamate transporters in the brain. Anat Sci Int 78:191–204

    Google Scholar 

  • Hisano S, Hoshi K, Ikeda Y, Maruyama D, Kanemoto M, Ichijo H, Kojima I, Takeda J, Nogami H (2000) Regional expression of a gene encoding a neuron-specific Na+-dependent inorganic phosphate cotransporter (DNPI) in the rat forebrain. Mol Brain Res 83:34–43

    Google Scholar 

  • Huffman RF, Henson OW (1990) The descending auditory pathway and acousticomotor systems: connections with the inferior colliculus. Brain Res Rev 15:295–323

    Google Scholar 

  • Kandler K, Friauf E (1993) Pre- and postnatal development of efferent connections of the cochlear nucleus in the rat. J Comp Neurol 328:161–184

    CAS  PubMed  Google Scholar 

  • Kandler K, Gillespie DC (2004) Glutamatergic synaptic transmission in the developing GABA/glycinergic MNTB-LSO pathway. Third Symposium on Molecular Mechanisms in Central Auditory Function, Plasticity and Disorders. Jackson Hole, Wyoming, June 25–27th 2004

  • Kaneko T, Fujiyama F (2002) Complementary distribution of vesicular glutamate transporters in the central nervous system. Neurosci Res 42:243–250

    Google Scholar 

  • Kaneko T, Fujiyama F, Hioki H (2002) Immunohistochemical localization of candidates for vesicular glutamate transporters in the rat brain. J Comp Neurol 444:39–62

    Article  CAS  PubMed  Google Scholar 

  • Kapfer C, Seidl AH, Schweizer H, Grothe B (2002) Experience-dependent refinement of inhibitory inputs to auditory coincidence-detector neurons. Nat Neurosci 5:247–253

    Google Scholar 

  • Kim G, Kandler K (2003) Elimination and strengthening of glycinergic/GABAergic connections during tonotopic map formation. Nat Neurosci 6:282–290

    Article  CAS  PubMed  Google Scholar 

  • Kiss A, Majorossy K (1983) Neuron morphology and synaptic architecture in the medial superior olivary nucleus. Light- and electron-microscopic studies in the cat. Exp Brain Res 52:315–327

    Google Scholar 

  • Kotak VC, Sanes DH (1997) Deafferentation weakens excitatory synapses in the developing central auditory system. Eur J Neurosci 9:2340–2347

    Google Scholar 

  • Kotak VC, Korada S, Schwartz IR, Sanes DH (1998) A developmental shift from GABAergic to glycinergic transmission in the central auditory system. J Neurosci 18:4646–4655

    Google Scholar 

  • Kulesza RJ, Berrebi AS (2000) Superior paraolivary nucleus of the rat is a GABAergic nucleus. J Assoc Res Otolaryngol 1:255–269

    Google Scholar 

  • Kulesza RJ, Spirou GA, Berrebi AS (2003) Physiological response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 89:2299–2312

    Google Scholar 

  • Kullmann PHM, Ene FA, Kandler K (2002) Glycinergic and GABAergic calcium responses in the developing lateral superior olive. Eur J Neurosci 15:1093–1104

    Google Scholar 

  • Liu GS (2003) Presynaptic control of quantal size: kinetic mechanisms for synaptic transmission and plasticity. Curr Opin Neurobiol 13:324–331

    Google Scholar 

  • Löhrke S, Friauf E (2002) Developmental distribution of the glutamate receptor subunits KA2, GluR6/7, and delta 1/2 in the rat medial nucleus of the trapezoid body. A quantitative image analysis. Cell Tissue Res 308:19–33

    Google Scholar 

  • Miyazaki T, Fukaya M, Shimizu H, Watanabe M (2003) Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci 17:2563–2572

    Google Scholar 

  • Morest DK (1968) The growth of synaptic endings in the mammalian brain: a study of the calyces of the trapezoid body. Z Anat Entwickl-Gesch 127:201–220

    Google Scholar 

  • Ni B, Rosteck PR Jr, Nadi NS, Paul SM (1994) Cloning and expression of a cDNA encoding a brain-specific Na+ -dependent inorganic phosphate cotransporter. Proc Natl Acad Sci USA 91:5607–5611

    Google Scholar 

  • Ni B, Wu X, Yan GM, Wang J, Paul SM (1995) Regional expression and cellular localization of the Na(+)-dependent inorganic phosphate cotransporter of rat brain. J Neurosci 15:5789–5799

    Google Scholar 

  • Oertel D, Wickesberg RE (1993) Glycinergic inhibition in the cochlear nuclei: evidence for tuberculoventral neurons being glycinergic. In: Merchán MA, Juiz JM, Godfrey DA, Mugnaini E (eds) The mammalian cochlear nuclei: organization and function. Plenum, New York, London, pp 225–237

    Google Scholar 

  • Raman IM, Zhang S, Trussell LO (1994) Pathway-specific variants of AMPA receptors and their contribution to neuronal signaling. J Neurosci 14:4998–5010

    Google Scholar 

  • Rietzel H, Friauf E (1998) Neuron types in the rat lateral superior olive and developmental changes in the complexity of their dendritic arbors. J Comp Neurol 390:20–40

    Google Scholar 

  • Robertson D (1996) Physiology and morphology of cells in the ventral nucleus of trapezoid body and rostral periolivary regions of the rat superior olivary complex studied in slices. Aud Neurosci 2:15–31

    Google Scholar 

  • Sanes DH, Siverls V (1991) Development and specificity of inhibitory terminal arborizations in the central nervous system. J Neurobiol 8:837–854

    Google Scholar 

  • Schäfer MKH, Varoqui H, Defamie N, Weihe E, Erickson JD (2002) Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons. J Biol Chem 277:50734–50748

    Google Scholar 

  • Schofield BR (1995) Projections from the cochlear nucleus to the superior paraolivary nucleus in guinea pigs. J Comp Neurol 360:135–149

    Google Scholar 

  • Schwartz IR (1992) The superior olivary complex and lateral lemniscal nuclei. In: Webster DB, Popper AN, Fay RR (eds) The mammalian auditory pathway: neuroanatomy. Springer, Berlin Heidelberg New York, pp 117–167

    Google Scholar 

  • Smith PH, Spirou GA (2002) From the cochlea to the cortex and back. In: Oertel D, Fay AN, Popper AN (eds) Integrative functions in the mammalian auditory pathway. Springer, Berlin Heidelberg New York, pp 6–71

    Google Scholar 

  • Sommer I, Lingenhöhl K, Friauf E (1993) Principal cells of the rat medial nucleus of the trapezoid body: an intracellular in vivo study of their physiology and morphology. Exp Brain Res 95:223–239

    Google Scholar 

  • Spangler KM, Warr WB (1991) The descending auditory system. In: Altschuler RA, Bobbin RP, Clopton BM, Hoffman DW (eds) Neurobiology of hearing: the central auditory system. Raven, New York, pp 27–45

    Google Scholar 

  • Spirou GA, Berrebi AS (1997) Glycine immunoreactivity in the lateral nucleus of the trapezoid body of the cat. J Comp Neurol 383:473–488

    Google Scholar 

  • Spirou GA, Rowland KC, Berrebi AS (1998) Ultrastructure of neurons and large synaptic terminals in the lateral nucleus of the trapezoid body of the cat. J Comp Neurol 398:257–272

    Google Scholar 

  • Srinivasan G, Friauf E, Löhrke S (2004) Functional glutamatergic and glycinergic inputs to several superior olivary nuclei of the rat revealed by optical imaging. Neuroscience 128:617–634

    Google Scholar 

  • Suneja SK, Benson CG, Gross J, Potashner SJ (1995) Evidence for glutamatergic projections from the cochlear nucleus to the superior olive and the ventral nucleus of the lateral lemniscus. J Neurochem 64:161–171

    Google Scholar 

  • Takamori S, Rhee JS, Rosenmund C, Jahn R (2000) Identification of a vesicular glutamate transporter that defines a glutamatergic phenotype in neurons. Nature 407:189–194

    Google Scholar 

  • Takamori S, Rhee JS, Rosenmund C, Jahn R (2001) Identification of differentiation-associated brain-specific phosphate transporter as a second vesicular glutamate transporter (VGLUT2). J Neurosci 21:RC182

    Google Scholar 

  • Takamori S, Malherbe P, Broger C, Jahn R (2002) Molecular cloning and functional characterization of human vesicular glutamate transporter 3. EMBO Rep 3:798–803

    Google Scholar 

  • Trussell LO (1999) Synaptic mechanisms for coding timing in auditory neurons. Annu Rev Physiol 61:477–496

    Google Scholar 

  • Varoqui H, Schäfer MKH, Zhu HM, Weihe E, Erickson JD (2002) Identification of the differentiation-associated Na+/P-I transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses. J Neurosci 22:142–155

    Google Scholar 

  • Vitten H, Reusch M, Friauf E, Löhrke S (2004) Expression of functional kainate and AMPA receptors in developing lateral superior olive neurons of the rat. J Neurobiol 59:272–288

    Google Scholar 

  • Wojcik SM, Rhee JS, Herzog E, Sigler A, Jahn R, Takamori S, Brose N, Rosenmund C (2004) An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci USA 101:7158–7163

    Google Scholar 

  • Wu SH, Kelly JB (1993) Response of neurons in the lateral superior olive and medial nucleus of the trapezoid body to repetitive stimulation: intracellular and extracellular recordings from mouse brain slice. Hearing Res 68:189–201

    Google Scholar 

  • Yin TCT (2002) Neural mechanisms of encoding binaural localization cues in the auditory brainstem. In: Oertel D, Fay RR, Popper AA (eds) Integrative functions in the mammalian auditory pathway. Springer, Berlin Heidelberg New York, pp 99–159

    Google Scholar 

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Acknowledgements

We thank Dr. S. El Mestikawy for the generous gift of the VGLUT antibodies and Dr. J.W. Deitmer and G. Neumann for help with the confocal microscope.

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  1. Abteilung Tierphysiologie, Fachbereich Biologie, Technische Universität Kaiserslautern, Kaiserslautern, Deutschland

    Peter Blaesse, Sascha Ehrhardt, Eckhard Friauf & Hans Gerd Nothwang

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  1. Peter Blaesse
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  2. Sascha Ehrhardt
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  3. Eckhard Friauf
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  4. Hans Gerd Nothwang
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Correspondence to Hans Gerd Nothwang.

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This work was supported by the Graduate Research School “Molecular, physiological and pharmacological analysis of cellular membrane transport”, DFG GRK 845/1.

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Blaesse, P., Ehrhardt, S., Friauf, E. et al. Developmental pattern of three vesicular glutamate transporters in the rat superior olivary complex. Cell Tissue Res 320, 33–50 (2005). https://doi.org/10.1007/s00441-004-1054-8

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