Artículo

Wedemeyer, C.; Martín, J.Z.S.; Ballestero, J.; Gómez-Casati, M.E.; Torbidoni, A.V.; Fuchs, P.A.; Bettler, B.; Elgoyhen, A.B.; Katz, E. "Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses" (2013) Journal of Neuroscience. 33(39):15477-15487
Estamos trabajando para conseguir la versión final de este artículo
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

The synapse between olivocochlear (OC) neurons and cochlear mechanosensory hair cells is cholinergic, fast, and inhibitory. The inhibitory sign of this cholinergic synapse is accounted for by the activation of Ca 2+ -permeable postsynaptic α9α10 nicotinic receptors coupled to the opening of hyperpolarizing Ca 2+ -activated small-conductance type 2 (SK2)K + channels. Acetylcholine (ACh) release at this synapse is supported by both P/Q- and N-type voltage-gated calcium channels (VGCCs). Although the OC synapse is cholinergic, an abundantOCGABAinnervation is present along themammaliancochlea. The role of this neurotransmitter at theOCefferent innervation, however, is for the most part unknown.Weshow thatGABAfails to evoke fast postsynaptic inhibitory currents in apical developing inner and outer hair cells. However, electrical stimulation ofOCefferent fibers activates presynapticGABA B(1a,2) receptors [GABAB (1a,2) Rs] that downregulate the amount of ACh released at the OC-hair cell synapse, by inhibiting P/Q-type VGCCs. We confirmed the expression of GABA B Rs at OC terminals contacting the hair cells by coimmunostaining for GFP and synaptophysin in transgenic mice expressing GABA B1 -GFP fusion proteins. Moreover, coimmunostaining with antibodies against the GABA synthetic enzyme glutamic acid decarboxylase and synaptophysin support the idea that GABA is directly synthesized at OC terminals contacting the hair cells during development. Thus, we demonstrate for the first time a physiological role for GABA in cochlear synaptic function. In addition, our data suggest that the GABA B1a isoform selectively inhibits release at efferent cholinergic synapses. © 2013 the authors.

Registro:

Documento: Artículo
Título:Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses
Autor:Wedemeyer, C.; Martín, J.Z.S.; Ballestero, J.; Gómez-Casati, M.E.; Torbidoni, A.V.; Fuchs, P.A.; Bettler, B.; Elgoyhen, A.B.; Katz, E.
Filiación:Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular Dr. Hector N. Torres, 1428 Buenos Aires, Argentina
Tercera Cátedra de Farmacología, 1121 Buenos Aires, Argentina
Johns Hopkins University, School of Medicine, Baltimore, MD 21205, United States
Department of Biomedicine, Institute of Physiology, University of Basel, CH-4056 Basel, Switzerland
Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Palabras clave:4 aminobutyric acid B (1a,2) receptor; 4 aminobutyric acid B receptor; baclofen; N type voltage gated calcium channel; neurotransmitter; P type voltage gated calcium channel; Q type voltage gated calcium channel; synaptophysin; unclassified drug; voltage gated calcium channel; acetylcholine release; animal tissue; article; cholinergic nerve cell; cochlea; controlled study; efferent nerve; electrophysiology; electrostimulation; hair cell; hearing; immunohistochemistry; inhibitory postsynaptic potential; mouse; nerve fiber; nonhuman; olivocochlea; priority journal; synapse; synaptic transmission; Acetylcholine; Animals; Calcium Channels, P-Type; Calcium Channels, Q-Type; Cholinergic Neurons; Electric Stimulation; gamma-Aminobutyric Acid; Hair Cells, Auditory; Inhibitory Postsynaptic Potentials; Mice; Mice, Inbred BALB C; Neurons, Efferent; Receptors, GABA-B; Synapses; Synaptophysin
Año:2013
Volumen:33
Número:39
Página de inicio:15477
Página de fin:15487
DOI: http://dx.doi.org/10.1523/JNEUROSCI.2554-13.2013
Título revista:Journal of Neuroscience
Título revista abreviado:J. Neurosci.
ISSN:02706474
CODEN:JNRSD
CAS:baclofen, 1134-47-0; Acetylcholine, N9YNS0M02X; Calcium Channels, P-Type; Calcium Channels, Q-Type; Receptors, GABA-B; Synaptophysin; gamma-Aminobutyric Acid, 56-12-2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v33_n39_p15477_Wedemeyer

Referencias:

  • Ballestero, J., Zorrilla de San Martín, J., Goutman, J., Elgoyhen, A.B., Fuchs, P.A., Katz, E., Short-term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells (2011) J Neurosci, 31, pp. 14763-14774. , CrossRef Medline
  • Batta, T.J., Panyi, G., Szucs, A., Sziklai, I., Regulation of the lateral wall stiffness by acetylcholine and GABA in the outer hair cells of the guinea pig (2004) Eur J Neurosci, 20, pp. 3364-3370. , CrossRef Medline
  • Bettler, B., Kaupmann, K., Mosbacher, J., Gassmann, M., Molecular structure and physiological functions of GABA(B) receptors (2004) Physiol Rev, 84, pp. 835-867. , CrossRef Medline
  • Beutner, D., Moser, T., The presynaptic function of mouse cochlear inner hair cells during development of hearing (2001) J Neurosci, 21, pp. 4593-4599. , Medline
  • Bianchi, M.S., Lux-Lantos, V.A., Bettler, B., Libertun, C., Expression of gamma-aminobutyric acid B receptor subunits in hypothalamus of male and female developing rats (2005) Brain Res Dev Brain Res, 160, pp. 124-129. , CrossRef Medline
  • Bittiger, H., Froestl, W., Mickel, S., Olpe, H.R., GABAB receptor antagonists: From synthesis to therapeutic applications (1993) Trends Pharmacol Sci, 14, pp. 391-394. , CrossRef Medline
  • Bowery, N.G., Bettler, B., Froestl, W., Gallagher, J.P., Marshall, F., Raiteri, M., Bonner, T.I., Enna, S.J., International Union of Pharmacology. XXXIII. Mammalian gamma-aminobutyric acid(B) receptors: Structure and function (2002) Pharmacol Rev, 54, pp. 247-264. , CrossRef Medline
  • Bray, J.G., Mynlieff, M., Involvement of protein kinase C and protein kinase A in the enhancement of L-type calcium current by GABAB receptor activation in neonatal hippocampus (2011) Neuroscience, 179, pp. 62-72. , CrossRef Medline
  • Brenowitz, S., Trussell, L.O., Minimizing synaptic depression by control of release probability (2001) J Neurosci, 21, pp. 1857-1867. , Medline
  • Brenowitz, S., David, J., Trussell, L., Enhancement of synaptic efficacy by presynaptic GABA(B) receptors (1998) Neuron, 20, pp. 135-141. , CrossRef Medline
  • Brown, M.C., Morphology and response properties of single olivocochlear fibers in the guinea pig (1989) Hear Res, 40, pp. 93-109. , CrossRef Medline
  • Casanova, E., Guetg, N., Vigot, R., Seddik, R., Julio-Pieper, M., Hyland, N.P., Cryan, J.F., Bettler, B., A mouse model for visualization of GABA(B) receptors (2009) Genesis, 47, pp. 595-602. , CrossRef Medline
  • Chalifoux, J.R., Carter, A.G., GABAB receptor modulation of synaptic function (2011) Curr Opin Neurobiol, 21, pp. 339-344. , CrossRef Medline
  • Del Castillo, J., Katz, B., Quantal components of the end-plate potential (1954) J Physiol, 124, pp. 560-573. , Medline
  • Duarte, C.B., Santos, P.F., Carvalho, A.P., Corelease of two functionally opposite neurotransmitters by retinal amacrine cells: Experimental evidence and functional significance (1999) J Neurosci Res, 58, pp. 475-479. , CrossRef Medline
  • Dulon, D., Lenoir, M., Cholinergic responses in developing outer hair cells of the rat cochlea (1996) Eur J Neurosci, 8, pp. 1945-1952. , CrossRef Medline
  • Elgoyhen, A., Vetter, D., Katz, E., Rothlin, C., Heinemann, S., Boulter, J., Alpha 10: A determinant of nicotinic cholinergic receptor function in mammalian vestibular and cochlear mechanosensory hair cells (2001) Proc Natl Acad Sci U S A, 98, pp. 3501-3506. , CrossRef Medline
  • Eybalin, M., Neurotransmitters and neuromodulators of the mammalian cochlea (1993) Physiol Rev, 73, pp. 309-373. , Medline
  • Farkas, Z., Kása, P., Balcar, V.J., Joó, F., Wolff, J.R., Type A and B GABA receptors mediate inhibition of acetylcholine release from cholinergic nerve terminals in the superior cervical ganglion of rat (1986) Neurochem Int, 8, pp. 565-572. , CrossRef Medline
  • Fex, J., Altschuler, R.A., Neurotransmitter-related immunocytochemistry of the organ of Corti (1986) Hear Res, 22, pp. 249-263. , CrossRef Medline
  • Fischl, M.J., Combs, T.D., Klug, A., Grothe, B., Burger, R.M., Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location (2012) J Physiol, 590, pp. 3047-3066. , CrossRef Medline
  • Gaiarsa, J.L., Tseeb, V., Ben-Ari, Y., Postnatal development of pre- and postsynaptic GABAB-mediated inhibitions in the CA3 hippocampal region of the rat (1995) J Neurophysiol, 73, pp. 246-255. , Medline
  • Gassmann, M., Bettler, B., Regulation of neuronal GABA(B) receptor functions by subunit composition (2012) Nat Rev Neurosci, 13, pp. 380-394. , CrossRef Medline
  • Gassmann, M., Shaban, H., Vigot, R., Sansig, G., Haller, C., Barbieri, S., Humeau, Y., Lecourtier, L., Redistribution of GABAB(1) protein and atypical GABAB responses in GABAB(2)-deficient mice (2004) J Neurosci, 24, pp. 6086-6097. , CrossRef Medline
  • Gitter, A.H., Zenner, H.P., gamma-Aminobutyric acid receptor activation of outer hair cells in the guinea pig cochlea (1992) Eur Arch Otorhinolaryngol, 249, pp. 62-65. , Medline
  • Glowatzki, E., Fuchs, P.A., Cholinergic synaptic inhibition of inner hair cells in the neonatal mammalian cochlea (2000) Science, 288, pp. 2366-2368. , CrossRef Medline
  • Gómez-Casati, M.E., Fuchs, P.A., Elgoyhen, A.B., Katz, E., Biophysical and pharmacological characterization of nicotinic cholinergic receptors in rat cochlear inner hair cells (2005) J Physiol, 566, pp. 103-118. , CrossRef Medline
  • Goutman, J.D., Fuchs, P.A., Glowatzki, E., Facilitating efferent inhibition of inner hair cells in the cochlea of the neonatal rat (2005) J Physiol, 566, pp. 49-59. , CrossRef Medline
  • Guinan, J.J., Physiology of the medial and lateral olivocochlear systems (2011) Auditory and Vestibular Efferents, pp. 39-81. , Ryugo DK, Fay RR, Popper AN, New York: Springer
  • He, D.Z., Dallos, P., Development of acetylcholine-induced responses in neonatal gerbil outer hair cells (1999) J Neurophysiol, 81, pp. 1162-1170. , Medline
  • Hubbard, J.I., Llinás, R.R., Quastel, D.M.J., (1969) Electrophysiological Analysis of Synaptic Transmission, , London: Edward Arnold
  • Johnson, S.L., Eckrich, T., Kuhn, S., Zampini, V., Franz, C., Ranatunga, K.M., Roberts, T.P., Marcotti, W., Positiondependent patterning of spontaneous action potentials in immature cochlear inner hair cells (2011) Nat Neurosci, 14, pp. 711-717. , CrossRef Medline
  • Jones, K.A., Borowsky, B., Tamm, J.A., Craig, D.A., Durkin, M.M., Dai, M., Yao, W.J., Gerald, C., GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2 (1998) Nature, 396, pp. 674-679. , CrossRef Medline
  • Katz, E., Elgoyhen, A.B., Gómez-Casati, M.E., Knipper, M., Vetter, D.E., Fuchs, P.A., Glowatzki, E., Developmental regulation of nicotinic synapses on cochlear inner hair cells (2004) J Neurosci, 24, pp. 7814-7820. , CrossRef Medline
  • Katz, E., Elgoyhen, A.B., Fuchs, P.A., Cholinergic inhibition of hair cells (2011) Auditory and Vestibular Efferents, pp. 103-133. , Ryugo DK, Fay RR, Popper AN, New York: Springer
  • Kaupmann, K., Malitschek, B., Schuler, V., Heid, J., Froestl, W., Beck, P., Mosbacher, J., Bettler, B., GABA(B)-receptor subtypes assemble into functional heteromeric complexes (1998) Nature, 396, pp. 683-687. , CrossRef Medline
  • Kuner, R., Köhr, G., Grünewald, S., Eisenhardt, G., Bach, A., Kornau, H.C., Role of heteromer formation in GABAB receptor function (1999) Science, 283, pp. 74-77. , CrossRef Medline
  • Lambert, N.A., Wilson, W.A., High-threshold Ca 2+ currents in rat hippocampal interneurones and their selective inhibition by activation of GABA(B) receptors (1996) J Physiol, 492, pp. 115-127. , Medline
  • Lee, S., Kim, K., Zhou, Z.J., Role of ACh-GABA cotransmission in detecting image motion and motion direction (2010) Neuron, 68, pp. 1159-1172. , CrossRef Medline
  • Liberman, M.C., Dodds, L.W., Pierce, S., Afferent and efferent innervation of the cat cochlea: Quantitative analysis with light and electron microscopy (1990) J Comp Neurol, 301, pp. 443-460. , CrossRef Medline
  • Lin, X., Chen, S., Chen, P., Activation of metabotropic GABAB receptors inhibited glutamate responses in spiral ganglion neurons of mice (2000) Neuroreport, 11, pp. 957-961. , CrossRef Medline
  • Maison, S.F., Adams, J.C., Liberman, M.C., Olivocochlear innervation in the mouse: Immunocytochemical maps, crossed versus uncrossed contributions, and transmitter colocalization (2003) J Comp Neurol, 455, pp. 406-416. , CrossRef Medline
  • Maison, S.F., Rosahl, T.W., Homanics, G.E., Liberman, M.C., Functional role of GABAergic innervation of the cochlea: Phenotypic analysis of mice lacking GABAA receptor subunits α1, α2, α5, α6, β2, β3, or δ (2006) J Neurosci, 26, pp. 10315-10326. , CrossRef Medline
  • Maison, S.F., Casanova, E., Holstein, G.R., Bettler, B., Liberman, M.C., Loss of GABA(B) receptors in cochlear neurons: Threshold elevation suggests modulation of outer hair cell function by type II afferent fibers (2009) J Assoc Res Otolaryngol, 10, pp. 50-63. , CrossRef Medline
  • Malitschek, B., Rüegg, D., Heid, J., Kaupmann, K., Bittiger, H., Fröstl, W., Bettler, B., Kuhn, R., Developmental changes of agonist affinity at GABABR1 receptor variants in rat brain (1998) Mol Cell Neurosci, 12, pp. 56-64. , CrossRef Medline
  • Mintz, I.M., Bean, B.P., GABAB receptor inhibition of P-type Ca 2+ channels in central neurons (1993) Neuron, 10, pp. 889-898. , CrossRef Medline
  • Misgeld, U., Bijak, M., Jarolimek, W., A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system (1995) Prog Neurobiol, 46, pp. 423-462. , CrossRef Medline
  • Oliver, D., Klöcker, N., Schuck, J., Baukrowitz, T., Ruppersberg, J.P., Fakler, B., Gating of Ca 2+ -activated K + channels controls fast inhibitory synaptic transmission at auditory outer hair cells (2000) Neuron, 26, pp. 595-601. , CrossRef Medline
  • Pérez-Garci, E., Gassmann, M., Bettler, B., Larkum, M.E., The GABAB1b isoform mediates long-lasting inhibition of dendritic Ca 2+ spikes in layer 5 somatosensory pyramidal neurons (2006) Neuron, 50, pp. 603-616. , CrossRef Medline
  • Rajan, R., Centrifugal pathways protect hearing sensitivity at the cochlea in noisy environments that exacerbate the damage induced by loud sound (2000) J Neurosci, 20, pp. 6684-6693. , Medline
  • Robertson, D., Gummer, M., Physiological and morphological characterization of efferent neurones in the guinea pig cochlea (1985) Hear Res, 20, pp. 63-77. , CrossRef Medline
  • Roux, I., Wersinger, E., McIntosh, J.M., Fuchs, P.A., Glowatzki, E., Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea (2011) J Neurosci, 31, pp. 15092-15101. , CrossRef Medline
  • Schuler, V., Lüscher, C., Blanchet, C., Klix, N., Sansig, G., Klebs, K., Schmutz, M., Korn, R., Epilepsy, hyperalgesia, impaired memory, and loss of pre- and postsynaptic GABA(B) responses in mice lacking GABA(B(1)) (2001) Neuron, 31, pp. 47-58. , CrossRef Medline
  • Schultheis, C., Brauner, M., Liewald, J.F., Gottschalk, A., Optogenetic analysis of GABAB receptor signaling in Caenorhabditis elegans motor neurons (2011) J Neurophysiol, 106, pp. 817-827. , CrossRef Medline
  • Shen, W., Slaughter, M.M., Metabotropic GABA receptors facilitate L-type and inhibit N-type calcium channels in single salamander retinal neurons (1999) J Physiol, 516, pp. 711-718. , CrossRef Medline
  • Simmons, D.D., Development of the inner ear efferent system across vertebrate species (2002) J Neurobiol, 53, pp. 228-250. , CrossRef Medline
  • Simmons, D.D., Mansdorf, N.B., Kim, J.H., Olivocochlear innervation of inner and outer hair cells during postnatal maturation: Evidence for a waiting period (1996) J Comp Neurol, 370, pp. 551-562. , CrossRef Medline
  • Taranda, J., Maison, S.F., Ballestero, J.A., Katz, E., Savino, J., Vetter, D.E., Boulter, J., Elgoyhen, A.B., A point mutation in the hair cell nicotinic cholinergic receptor prolongs cochlear inhibition and enhances noise protection (2009) PLoS Biol, 7, pp. e18. , CrossRef Medline
  • Thompson, G.C., Cortez, A.M., Igarashi, M., GABA-like immunoreactivity in the squirrel monkey organ of Corti (1986) Brain Res, 372, pp. 72-79. , CrossRef Medline
  • Thompson, S.M., Capogna, M., Scanziani, M., Presynaptic inhibition in the hippocampus (1993) Trends Neurosci, 16, pp. 222-227. , CrossRef Medline
  • Vetter, D.E., Adams, J.C., Mugnaini, E., Chemically distinct rat olivocochlear neurons (1991) Synapse, 7, pp. 21-43. , CrossRef Medline
  • Vetter, D.E., Katz, E., Maison, S.F., Taranda, J., Turcan, S., Ballestero, J., Liberman, M.C., Boulter, J., The alpha10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system (2007) Proc Natl Acad Sci U S A, 104, pp. 20594-20599. , CrossRef Medline
  • Vigot, R., Barbieri, S., Bräuner-Osborne, H., Turecek, R., Shigemoto, R., Zhang, Y.P., Luján, R., Bettler, B., Differential compartmentalization and distinct functions of GABAB receptor variants (2006) Neuron, 50, pp. 589-601. , CrossRef Medline
  • White, J.H., Wise, A., Main, M.J., Green, A., Fraser, N.J., Disney, G.H., Barnes, A.A., Marshall, F.H., Heterodimerization is required for the formation of a functional GABA(B) receptor (1998) Nature, 396, pp. 679-682. , CrossRef Medline
  • Yoon, E.J., Gerachshenko, T., Spiegelberg, B.D., Alford, S., Hamm, H.E., Gbetagamma interferes with Ca 2+ -dependent binding of synaptotagmin to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex (2007) Mol Pharmacol, 72, pp. 1210-1219. , CrossRef Medline
  • Zenner, H.P., Gitter, A.H., Rudert, M., Ernst, A., Stiffness, compliance, elasticity and force generation of outer hair cells (1992) Acta Otolaryngol, 112, pp. 248-253. , Medline
  • Zorrilla de San Martín, J., Pyott, S., Ballestero, J., Katz, E., Ca 2+ and Ca 2+ -activated K + channels that support and modulate transmitter release at the olivocochlear efferent-inner hair cell synapse (2010) J Neurosci, 30, pp. 12157-12167. , CrossRef Medline

Citas:

---------- APA ----------
Wedemeyer, C., Martín, J.Z.S., Ballestero, J., Gómez-Casati, M.E., Torbidoni, A.V., Fuchs, P.A., Bettler, B.,..., Katz, E. (2013) . Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses. Journal of Neuroscience, 33(39), 15477-15487.
http://dx.doi.org/10.1523/JNEUROSCI.2554-13.2013
---------- CHICAGO ----------
Wedemeyer, C., Martín, J.Z.S., Ballestero, J., Gómez-Casati, M.E., Torbidoni, A.V., Fuchs, P.A., et al. "Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses" . Journal of Neuroscience 33, no. 39 (2013) : 15477-15487.
http://dx.doi.org/10.1523/JNEUROSCI.2554-13.2013
---------- MLA ----------
Wedemeyer, C., Martín, J.Z.S., Ballestero, J., Gómez-Casati, M.E., Torbidoni, A.V., Fuchs, P.A., et al. "Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses" . Journal of Neuroscience, vol. 33, no. 39, 2013, pp. 15477-15487.
http://dx.doi.org/10.1523/JNEUROSCI.2554-13.2013
---------- VANCOUVER ----------
Wedemeyer, C., Martín, J.Z.S., Ballestero, J., Gómez-Casati, M.E., Torbidoni, A.V., Fuchs, P.A., et al. Activation of presynaptic GABA b(1a,2) receptors inhibits synaptic transmission at mammalian inhibitory cholinergic olivocochlear-hair cell synapses. J. Neurosci. 2013;33(39):15477-15487.
http://dx.doi.org/10.1523/JNEUROSCI.2554-13.2013