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Brain Structure and Function

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29.01.2016 | Original Article

Expression of glycine receptor alpha 3 in the rat trigeminal neurons and central boutons in the brainstem

verfasst von: Jin Young Bae, Won Mah, Jong-Cheol Rah, Sook Kyung Park, Yong Chul Bae

Erschienen in: Brain Structure and Function | Ausgabe 9/2016

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Abstract

Increasing evidence shows that the homomeric glycine receptor is expressed in axon terminals and is involved in the presynaptic modulation of transmitter release. However, little is known about the expression of the glycine receptor, implicated in the presynaptic modulation of sensory transmission in the primary somatosensory neurons and their central boutons. To address this, we investigated the expression of glycine receptor subunit alpha 3 (GlyRα3) in the neurons in the trigeminal ganglion and axon terminals in the 1st relay nucleus of the brainstem by light- and electron-microscopic immunohistochemistry. Trigeminal primary sensory neurons were GlyRα3-immunopositive/gephyrin-immunonegative (indicating homomeric GlyR), whereas GlyRα3/gephyrin immunoreactivity (indicating heteromeric GlyR) was observed in dendrites. GlyRα3 immunoreactivity was also found in the central boutons of primary afferents but far from the presynaptic site and in dendrites at subsynaptic sites. Boutons expressing GlyRα3 contained small round vesicles, formed asymmetric synapses with dendrites and were immunoreactive for glutamate. These findings suggest that trigeminal primary afferent boutons receive presynaptic modulation via homomeric, extrasynaptic GlyRα3, and that different subtypes of GlyR may be involved in pre- and postsynaptic inhibition.

Alvarez FJ (1998) Anatomical basis of presynaptic inhibition of primary afferent fibers. In: Rudomin P, Romo R, Mendell LM (eds) Presynaptic inhibition and neural control. Oxford University Press, New York, pp 13–49

Alvarez F, Kavookjian A, Light A (1992) Synaptic interactions between GABA-immunoreactive profiles and the terminals of functionally defined myelinated nociceptors in the monkey and cat spinal cord. J Neurosci 12:2901–2917PubMed

Bae YC, Nakagawa S, Yoshida A, Nagase Y, Takemura M, Shigenaga Y (1994) Morphology and synaptic connections of slowly adapting periodontal afferent terminals in the trigeminal subnuclei principalis and oralis of the cat. J Comp Neurol 348:121–132CrossRefPubMed

Bae YC, Ihn HJ, Park MJ, Ottersen OP, Moritani M, Yoshida A, Shigenaga Y (2000) Identification of signal substances in synapses made between primary afferents and their associated axon terminals in the rat trigeminal sensory nuclei. J Comp Neurol 418:299–309CrossRefPubMed

Bae YC, Choi BJ, Lee MG, Lee HJ, Park KP, Zhang LF, Honma S, Fukami H, Yoshida A, Ottersen OP, Shigenaga Y (2002) Quantitative ultrastructural analysis of glycine- and gamma-aminobutyric acid-immunoreactive terminals on trigeminal alpha- and gamma-motoneuron somata in the rat. J Comp Neurol 442:308–319CrossRefPubMed

Bae YC, Kim JP, Choi BJ, Park KP, Choi MK, Moritani M, Yoshida A, Shigenaga Y (2003) Synaptic organization of tooth pulp afferent terminals in the rat trigeminal sensory nuclei. J Comp Neurol 463:13–24CrossRefPubMed

Bae YC, Ahn HJ, Park KP, Kim HN, Paik SK, Bae JY, Lee HW, Kim KH, Yoshida A, Moritani M, Shigenaga Y (2005a) The synaptic microcircuitry associated with primary afferent terminals in the interpolaris and caudalis of trigeminal sensory nuclear complex. Brain Res 1060:118–125CrossRefPubMed

Bae YC, Park KS, Bae JY, Paik SK, Ahn DK, Moritani M, Yoshida A, Shigenaga Y (2005b) GABA and glycine in synaptic microcircuits associated with physiologically characterized primary afferents of cat trigeminal principal nucleus. Exp Brain Res 162:449–457CrossRefPubMed

Bae JY, Kim JH, Cho YS, Mah W, Bae YC (2015) Quantitative analysis of afferents expressing substance P, calcitonin gene-related peptide, isolectin B4, neurofilament 200, and peripherin in the sensory root of the rat trigeminal ganglion. J Comp Neurol 523:126–138CrossRefPubMed

Beato M, Sivilotti LG (2007) Single-channel properties of glycine receptors of juvenile rat spinal motoneurones in vitro. J Physiol 580:497–506CrossRefPubMedPubMedCentral

Bormann J, Rundström N, Betz H, Langosch D (1993) Residues within transmembrane segment M2 determine chloride conductance of glycine receptor homo- and hetero-oligomers. EMBO J 12:3729–3737PubMedPubMedCentral

Boron WF, Boulpaep EL (2012) Medical physiology: a cellular and molecular approach. Saunders/Elsevier, Philadelphia

Broman J, Anderson S, Ottersen OP (1993) Enrichment of glutamate-like immunoreactivity in primary afferent terminals throughout the spinal cord dorsal horn. Eur J Neurosci 5:1050–1061CrossRefPubMed

Chu Y, Fioravante D, Thanawala M, Leitges M, Regehr WG (2012) Calcium-dependent isoforms of protein kinase C mediate glycine-induced synaptic enhancement at the calyx of held. J Neurosci 32:13796–13804CrossRefPubMedPubMedCentral

Debanne D, Campanac E, Bialowas A, Carlier E, Alcaraz G (2011) Axon physiology. Physiol Rev 91:555–602CrossRefPubMed

Deleuze C, Runquist M, Orcel H, Rabié A, Dayanithi G, Alonso G, Hussy N (2005) Structural difference between heteromeric somatic and homomeric axonal glycine receptors in the hypothalamo-neurohypophysial system. Neuroscience 135:475–483CrossRefPubMed

Désarmenien M, Feltz P, Occhipinti G, Santangelo F, Schlichter R (1984) Coexistence of GABAA and GABAB receptors on Aδ and C primary afferents. Br J Pharmacol 81:327–333CrossRefPubMedPubMedCentral

Fekete CD, Chiou T-T, Miralles CP, Harris RS, Fiondella CG, Loturco JJ, De Blas AL (2015) In vivo clonal overexpression of neuroligin 3 and neuroligin 2 in neurons of the rat cerebral cortex: differential effects on GABAergic synapses and neuronal migration. J Comp Neurol 523:1359–1378CrossRefPubMedPubMedCentral

Gray EG (1962) A morphological basis for pre-synaptic inhibition? Nature 193:82–83CrossRefPubMed

Handford CA, Lynch JW, Baker E, Webb GC, Ford JH, Sutherland GR, Schofield PR (1996) The human glycine receptor β subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes. Mol Brain Res 35:211–219CrossRefPubMed

Harper AA, Lawson SN (1985) Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurones. J Physiol 359:31–46CrossRefPubMedPubMedCentral

Harvey RJ, Depner UB, Wässle H, Ahmadi S, Heindl C, Reinold H, Smart TG, Harvey K, Schütz B, Abo-Salem OM, Zimmer A, Poisbeau P, Welzl H, Wolfer DP, Betz H, Zeilhofer HU, Müller U (2004) GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization. Science 304:884–887CrossRefPubMed

Harvey VL, Caley A, Müller UC, Harvey RJ, Dickenson AH (2009) A selective role for alpha3 subunit glycine receptors in inflammatory pain. Front Mol Neurosci 2:14CrossRefPubMedPubMedCentral

Haverkamp S, Müller U, Harvey K et al (2003) Diversity of glycine receptors in the mouse retina: localization of the alpha3 subunit. J Comp Neurol 465:524–539CrossRefPubMed

Hruskova B, Trojanova J, Kulik A, Kralikova M, Pysanenko K, Bures Z, Syka J, Trussell LO, Turecek R (2012) Differential distribution of glycine receptor subtypes at the rat calyx of held synapse. J Neurosci 32:17012–17024CrossRefPubMedPubMedCentral

Huang H, Trussell LO (2008) Control of presynaptic function by a persistent Na(+) current. Neuron 60:975–979CrossRefPubMedPubMedCentral

Hussy N, Deleuze C, Pantaloni A, Desarménien MG, Moos F (1997) Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation. J Physiol 502(3):609–621CrossRefPubMedPubMedCentral

Ichikawa H, Schulz S, Höllt V, Sugimoto T (2003) The somatostatin SST2A receptor in the rat trigeminal ganglion. Neuroscience 120:807–813CrossRefPubMed

Javdani F, Holló K, Hegedűs K, Kis G, Hegyi Z, Dócs K, Kasugai Y, Fukazawa Y, Shigemoto R, Antal M (2015) Differential expression patterns of K(+)/Cl(−) cotransporter 2 in neurons within the superficial spinal dorsal horn of rats. J Comp Neurol. doi:10.1002/cne.23774 PubMed

Kim Y, Trussell LO (2009) Negative shift in the glycine reversal potential mediated by a Ca²⁺- and pH-dependent mechanism in interneurons. J Neurosci 29:11495–11510CrossRefPubMedPubMedCentral

Kirsch J, Betz H (1998) Glycine-receptor activation is required for receptor clustering in spinal neurons. Nature 392:717–720CrossRefPubMed

Kneussel M, Brandstatter JH, Laube B, Stahl S, Muller U, Betz H (1999) Loss of Postsynaptic GABAA Receptor Clustering in Gephyrin-Deficient Mice. J Neurosci 19:9289–9297PubMed

Kopp-Scheinpflug C, Dehmel S, Tolnai S, Dietz B, Milenkovic I, Rübsamen R (2008) Glycine-mediated changes of onset reliability at a mammalian central synapse. Neuroscience 157:432–445CrossRefPubMed

Kubota H, Alle H, Betz H, Geiger JRP (2010) Presynaptic glycine receptors on hippocampal mossy fibers. Biochem Biophys Res Commun 393:587–591CrossRefPubMed

Labrakakis C, Tong C-K, Weissman T, Torsney C, MacDermott AB (2003) Localization and function of ATP and GABAA receptors expressed by nociceptors and other postnatal sensory neurons in rat. J Physiol 549:131–142CrossRefPubMedPubMedCentral

Legendre P (2001) The glycinergic inhibitory synapse. Cell Mol Life Sci 58:760–793CrossRefPubMed

Legendre P (2002) Desensitization of homomeric alpha 1 glycine receptor increases with receptor density. Mol Pharmacol 62:817–827CrossRefPubMed

Levi S, Vannier C, Triller A (1998) Strychnine-sensitive stabilization of postsynaptic glycine receptor clusters. J Cell Sci 111:335–345PubMed

Lorenzo L-E, Godin AG, Wang F, St-Louis M, Carbonetto S, Wiseman PW, Ribeiro-da-Silva A, De Koninck Y (2014) Gephyrin clusters are absent from small diameter primary afferent terminals despite the presence of GABA(A) receptors. J Neurosci 34:8300–8317CrossRefPubMed

Lynch JW (2009) Native glycine receptor subtypes and their physiological roles. Neuropharmacology 56:303–309CrossRefPubMed

Matsubara A, Laake JH, Davanger S, Usami S, Ottersen OP (1996) Organization of AMPA Receptor Subunits at a Glutamate synapse: a quantitative immunogold analysis of hair cell synapses in the rat organ of corti. J Neurosci 16:4457–4467PubMed

Mitchell K, Spike RC, Todd AJ (1993) An immunocytochemical study of glycine receptor and GABA in laminae I–III of rat spinal dorsal horn. J Neurosci 13:2371–2381PubMed

Mohammadi B, Krampfl K, Cetinkaya C, Moschref H, Grosskreutz J, Dengler R, Bufler J (2003) Kinetic analysis of recombinant mammalian α1 and α1β glycine receptor channels. Eur Biophys J 32:529–536CrossRefPubMed

Moon YS, Paik SK, Seo JH, Yi HW, Cho YS, Moritani M, Yoshida A, Ahn DK, Kim YS, Bae YC (2008) GABA- and glycine-like immunoreactivity in axonal endings presynaptic to the vibrissa afferents in the cat trigeminal interpolar nucleus. Neuroscience 152:138–145CrossRefPubMed

Muller E, Le-Corronc H, Legendre P (2008) Extrasynaptic and postsynaptic receptors in glycinergic and GABAergic neurotransmission: a division of labor? Front Mol Neurosci 1:3CrossRefPubMedPubMedCentral

Ottersen OP, Storm-Mathisen J, Madsen S, Skumlien S, Strømhaug J (1986) Evaluation of the immunocytochemical method for amino acids. Med Biol 64:147–158PubMed

Paik SK, Bae JY, Park SE, Moritani M, Yoshida A, Yeo EJ, Choi KS, Ahn DK, Moon C, Shigenaga Y, Bae YC (2007) Developmental changes in distribution of γ-aminobutyric acid- and glycine-immunoreactive boutons on rat trigeminal motoneurons. I. Jaw-closing motoneurons. J Comp Neurol 503:779–789CrossRefPubMed

Paik SK, Lee HJ, Choi MK, Cho YS, Park MJ, Moritani M, Yoshida A, Kim YS, Bae YC (2009) Ultrastructural analysis of glutamate-, GABA-, and glycine-immunopositive boutons from supratrigeminal premotoneurons in the rat trigeminal motor nucleus. J Neurosci Res 87:1115–1122CrossRefPubMed

Paik SK, Park SK, Jin JK, Bae JY, Choi SJ, Yoshida A, Ahn DK, Bae YC (2011) Ultrastructural analysis of glutamate-immunopositive synapses onto the rat jaw-closing motoneurons during postnatal development. J Neurosci Res 89:153–161CrossRefPubMed

Paik SK, Kwak WK, Bae JY, Na YK, Park SY, Yi HW, Ahn DK, Ottersen OP, Yoshida A, Bae YC (2012a) Development of γ-aminobutyric acid-, glycine-, and glutamate-immunopositive boutons on rat jaw-opening motoneurons. J Comp Neurol 520:1212–1226CrossRefPubMed

Paik SK, Kwak MK, Bae JY, Yi HW, Yoshida A, Ahn DK, Bae YC (2012b) γ-Aminobutyric acid-, glycine-, and glutamate-immunopositive boutons on mesencephalic trigeminal neurons that innervate jaw-closing muscle spindles in the rat: ultrastructure and development. J Comp Neurol 520:3414–3427CrossRefPubMed

Price GD, Trussell LO (2006) Estimate of the chloride concentration in a central glutamatergic terminal: a gramicidin perforated-patch study on the calyx of held. J Neurosci 26:11432–11436CrossRefPubMed

Ribeiro-da-Silva A, Coimbra A (1982) Two types of synaptic glomeruli and their distribution in laminae I-III of the rat spinal cord. J Comp Neurol 209:176–186CrossRefPubMed

Sassoe-Pognetto M, Wassle H, Grunert U (1994) Glycinergic synapses in the rod pathway of the rat retina: cone bipolar cells express the alpha 1 subunit of the glycine receptor. J Neurosci 14:5131–5146PubMed

Shigenaga Y, Yoshida A, Tsuru K, Mitsuhiro Y, Otani K, Cao CQ (1988) Physiological and morphological characteristics of cat masticatory motoneurons—intracellular injection of HRP. Brain Res 461:238–256CrossRefPubMed

Shigenaga Y, Moritani M, Oh SJ, Park KP, Paik SK, Bae JY, Kim HN, Ma SK, Park CW, Yoshida A, Ottersen OP, Bae YC (2005) The distribution of inhibitory and excitatory synapses on single, reconstructed jaw-opening motoneurons in the cat. Neuroscience 133:507–518CrossRefPubMed

Singer JH, Berger AJ (2000) Development of inhibitory synaptic transmission to motoneurons. Brain Res Bull 53:553–560CrossRefPubMed

Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Haug F-MŠ, Ottersen OP (1983) First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301:517–520CrossRefPubMed

Sugimoto T, Fujiyoshi Y, He Y-F, Xiao C, Ichikawa H (1997a) Trigeminal primary projection to the rat brainstem sensory trigeminal nuclear complex and surrounding structures revealed by anterograde transport of cholera toxin B subunit-conjugated and Bandeiraea simplicifolia isolectin B4-conjugated horseradish peroxidase. Neurosci Res 28:361–371CrossRefPubMed

Sugimoto T, Fujiyoshi Y, Xiao C, He YF, Ichikawa H (1997b) Central projection of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive trigeminal primary neurons in the rat. J Comp Neurol 378:425–442CrossRefPubMed

Takahashi T, Momiyama A, Hirai K, Hishinuma F, Akagi H (1992) Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Neuron 9:1155–1161CrossRefPubMed

Takumi Y, Ramírez-León V, Laake P, Rinvik E, Ottersen OP (1999) Different modes of expression of AMPA and NMDA receptors in hippocampal synapses. Nat Neurosci 2:618–624CrossRefPubMed

Todd AJ, Spike RC, Chong D, Neilson M (1995) The Relationship Between Glycine and Gephyrin in Synapses of the Rat Spinal Cord. Eur J Neurosci 7:1–11CrossRefPubMed

Todd AJ, Watt C, Spike RC, Sieghart W (1996) Colocalization of GABA, glycine, and their receptors at synapses in the rat spinal cord. J Neurosci 16:974–982PubMed

Triner JC (2013) Defining neurochemical properties and functions of primary sensory neurons in the rat trigeminal ganglion, Dissertation, University of Plymouth

Trojanova J, Kulik A, Janacek J, Kralikova M, Syka J, Turecek R (2014) Distribution of glycine receptors on the surface of the mature calyx of Held nerve terminal. Front Neural Circuits 8:120CrossRefPubMedPubMedCentral

Turecek R, Trussell LO (2001) Presynaptic glycine receptors enhance transmitter release at a mammalian central synapse. Nature 411:587–590CrossRefPubMed

Turecek R, Trussell LO (2002) Reciprocal developmental regulation of presynaptic ionotropic receptors. Proc Natl Acad Sci USA 99:13884–13889CrossRefPubMedPubMedCentral

Watson AHD (2004) Synaptic interactions between the terminals of slow-adapting type II mechanoreceptor afferents and neurones expressing gamma-aminobutyric acid- and glycine-like immunoreactivity in the rat spinal cord. J Comp Neurol 471:168–179CrossRefPubMed

Witschi R, Punnakkal P, Paul J, Walczak J-S, Cervero F, Fritschy J-M, Kuner R, Keist R, Rudolph U, Zeilhofer HU (2011) Presynaptic alpha2-GABAA receptors in primary afferent depolarization and spinal pain control. J Neurosci 31:8134–8142CrossRefPubMedPubMedCentral

Wotherspoon G, Priestley JV (1999) Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells. Neuroscience 95:465–471CrossRef

Xiong W, Cui T, Cheng K, Yang F, Chen S-R, Willenbring D, Guan Y, Pan H-L, Ren K, Xu Y, Zhang L (2012) Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors. J Exp Med 209:1121–1134CrossRefPubMedPubMedCentral

Xiong W, Chen S-R, He L, Cheng K, Zhao Y-L, Chen H, Li D-P, Homanics GE, Peever J, Rice KC, Wu L, Pan H-L, Zhang L (2014) Presynaptic glycine receptors as a potential therapeutic target for hyperekplexia disease. Nat Neurosci 17:232–239CrossRefPubMedPubMedCentral

Zhang N, Ottersen OP (1992) Differential cellular distribution of two sulphur-containing amino acids in rat cerebellum. Exp Brain Res 90:11–20CrossRefPubMed

Titel: Expression of glycine receptor alpha 3 in the rat trigeminal neurons and central boutons in the brainstem
verfasst von: Jin Young Bae
Won Mah
Jong-Cheol Rah
Sook Kyung Park
Yong Chul Bae
Publikationsdatum: 29.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 9/2016
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-016-1190-4

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