메뉴 건너뛰기




Volumn 49, Issue 1, 2003, Pages 29-46

Synaptic nests lack glutamate transporters in the cochlear nucleus of the mouse

Author keywords

Astrocyte; Auditory; Electron microscopy; Excitotoxicity; Lateral diffusion; Plasticity; Postembedding immunogold; Preembedding immunocytochemistry; Spillover

Indexed keywords

GLUTAMATE TRANSPORTER; GLUTAMATE TRANSPORTER EAAC1; GLUTAMATE TRANSPORTER GLAST; GLUTAMATE TRANSPORTER GLT1; GLUTAMIC ACID; PEROXIDASE; UNCLASSIFIED DRUG;

EID: 0037799176     PISSN: 08874476     EISSN: None     Source Type: Journal    
DOI: 10.1002/syn.10201     Document Type: Article
Times cited : (7)

References (52)
  • 1
    • 0030932152 scopus 로고    scopus 로고
    • Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance
    • Arriza JL, Eliasof S, Kavanaugh MP, Amara SG. 1997. Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proc Natl Acad Sci USA 94:4155-4160.
    • (1997) Proc Natl Acad Sci USA , vol.94 , pp. 4155-4160
    • Arriza, J.L.1    Eliasof, S.2    Kavanaugh, M.P.3    Amara, S.G.4
  • 2
    • 0031046153 scopus 로고    scopus 로고
    • Extrasynaptic glutamate spillover in the hippocampus: Dependence on temperature and the role of active glutamate uptake
    • Asztely F, Erdemli G, Kullmann DM. 1997. Extrasynaptic glutamate spillover in the hippocampus: dependence on temperature and the role of active glutamate uptake. Neuron 18:281-293.
    • (1997) Neuron , vol.18 , pp. 281-293
    • Asztely, F.1    Erdemli, G.2    Kullmann, D.M.3
  • 3
    • 0035887734 scopus 로고    scopus 로고
    • An evaluation of synapse independence
    • Barbour B. 2001. An evaluation of synapse independence. J Neurosci 21:7969-7984.
    • (2001) J Neurosci , vol.21 , pp. 7969-7984
    • Barbour, B.1
  • 4
    • 0031952493 scopus 로고    scopus 로고
    • Differential expression of the metabotropic glutamate receptor mGluR1α by neurons and axons in the cochlear nucleus: In situ hybridization and immunohistochemistry
    • Bilak SR, Morest DK. 1998. Differential expression of the metabotropic glutamate receptor mGluR1α by neurons and axons in the cochlear nucleus: in situ hybridization and immunohistochemistry. Synapse 28:251-270.
    • (1998) Synapse , vol.28 , pp. 251-270
    • Bilak, S.R.1    Morest, D.K.2
  • 5
    • 0030298342 scopus 로고    scopus 로고
    • Differential expression of N-methyl-D-aspartate receptor in the cochlear nucleus of the mouse
    • Bilak MM, Bilak SR, Morest DK. 1996. Differential expression of N-methyl-D-aspartate receptor in the cochlear nucleus of the mouse. Neuroscience 75:1075-1097.
    • (1996) Neuroscience , vol.75 , pp. 1075-1097
    • Bilak, M.M.1    Bilak, S.R.2    Morest, D.K.3
  • 6
    • 0034659742 scopus 로고    scopus 로고
    • Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse
    • Carter AG, Regehr WG. 2000. Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J Neurosci 20:4423-4434.
    • (2000) J Neurosci , vol.20 , pp. 4423-4434
    • Carter, A.G.1    Regehr, W.G.2
  • 7
    • 0029114107 scopus 로고
    • Glutamate transporters in glial plasma membranes: Highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry
    • Chaudhry FA, Lehre KP, van Lookeren Campagne M, Ottersen OP, Danbolt NC, Storm-Mathisen J. 1995. Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry. Neuron 15:711-720.
    • (1995) Neuron , vol.15 , pp. 711-720
    • Chaudhry, F.A.1    Lehre, K.P.2    Van Lookeren Campagne, M.3    Ottersen, O.P.4    Danbolt, N.C.5    Storm-Mathisen, J.6
  • 8
    • 0031918486 scopus 로고    scopus 로고
    • EAAC1, a high-affinity glutamate transporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex
    • Conti F, DeBiasi S, Minelli A, Rothstein JD, Melone M. 1998. EAAC1, a high-affinity glutamate transporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. Cerebral Cortex 8:108-116.
    • (1998) Cerebral Cortex , vol.8 , pp. 108-116
    • Conti, F.1    DeBiasi, S.2    Minelli, A.3    Rothstein, J.D.4    Melone, M.5
  • 9
    • 0035001341 scopus 로고    scopus 로고
    • Glutamate uptake
    • Danbolt NC. 2001. Glutamate uptake. Prog Neurobiol 65:1-105.
    • (2001) Prog Neurobiol , vol.65 , pp. 1-105
    • Danbolt, N.C.1
  • 10
    • 0030947654 scopus 로고    scopus 로고
    • Transporters buffer synaptically released glutamate on a submillisecond time scale
    • Diamond JS, Jahr CE. 1997. Transporters buffer synaptically released glutamate on a submillisecond time scale. J Neurosci 17: 4672-4687.
    • (1997) J Neurosci , vol.17 , pp. 4672-4687
    • Diamond, J.S.1    Jahr, C.E.2
  • 11
    • 0029076899 scopus 로고
    • An excitatory amino-acid transporter with properties of a ligand-gated chloride channel
    • Fairman WA, Vandenberg RJ, Arriza JL, Kavanaugh MP, Amara SG. 1995. An excitatory amino-acid transporter with properties of a ligand-gated chloride channel. Nature 375:599-603.
    • (1995) Nature , vol.375 , pp. 599-603
    • Fairman, W.A.1    Vandenberg, R.J.2    Arriza, J.L.3    Kavanaugh, M.P.4    Amara, S.G.5
  • 12
    • 0016220006 scopus 로고
    • Synaptic organization of the substantia gelatinosa glomeruli in the spinal trigeminal nucleus of the adult cat
    • Gobel S. 1974. Synaptic organization of the substantia gelatinosa glomeruli in the spinal trigeminal nucleus of the adult cat. J Neurocytol 3:219-243.
    • (1974) J Neurocytol , vol.3 , pp. 219-243
    • Gobel, S.1
  • 13
    • 0014634342 scopus 로고
    • Fine structural studies of the main sensory trigeminal nucleus in the cat and rat
    • Gobel S, Dubner R. 1969. Fine structural studies of the main sensory trigeminal nucleus in the cat and rat. J Comp Neurol 137:459-493.
    • (1969) J Comp Neurol , vol.137 , pp. 459-493
    • Gobel, S.1    Dubner, R.2
  • 14
    • 0034554777 scopus 로고    scopus 로고
    • Exacerbation of noise-induced hearing loss in mice lacking the glutamate transporter GLAST
    • Hakuba N, Koga K, Gyo K, Usami SI, Tanaka K. 2000. Exacerbation of noise-induced hearing loss in mice lacking the glutamate transporter GLAST. J Neurosci 20:8750-8753.
    • (2000) J Neurosci , vol.20 , pp. 8750-8753
    • Hakuba, N.1    Koga, K.2    Gyo, K.3    Usami, S.I.4    Tanaka, K.5
  • 15
    • 0033566309 scopus 로고    scopus 로고
    • Cochlear nerve projections to the small cell shell of the cochlear nucleus: The neuroanatomy of extremely thin sensory axons
    • Hurd LB, Hutson KA, Morest DK. 1999. Cochlear nerve projections to the small cell shell of the cochlear nucleus: the neuroanatomy of extremely thin sensory axons. Synapse 33:83-117.
    • (1999) Synapse , vol.33 , pp. 83-117
    • Hurd, L.B.1    Hutson, K.A.2    Morest, D.K.3
  • 16
    • 0029821375 scopus 로고    scopus 로고
    • Fine structure of the cell clusters in the cochlear nerve root: Stellate, granule, and mitt cells offer insights into the synaptic organization of local circuit neurons
    • Hutson KA, Morest DK. 1996. Fine structure of the cell clusters in the cochlear nerve root: stellate, granule, and mitt cells offer insights into the synaptic organization of local circuit neurons. J Comp Neurol 371:397-414.
    • (1996) J Comp Neurol , vol.371 , pp. 397-414
    • Hutson, K.A.1    Morest, D.K.2
  • 17
    • 0033151664 scopus 로고    scopus 로고
    • Glutamate spillover mediates excitatory transmission in the rat olfactory bulb
    • Isaacson JS. 1999. Glutamate spillover mediates excitatory transmission in the rat olfactory bulb. Neuron 23:377-384.
    • (1999) Neuron , vol.23 , pp. 377-384
    • Isaacson, J.S.1
  • 18
    • 0031770913 scopus 로고    scopus 로고
    • Metabotropic glutamate receptors are associated with non-synaptic appendages of unipolar brush cells in rat cerebellar cortex and cochlear nuclear complex
    • Jaarsma D, Dino MR, Ohishi H, Shigemoto R, Mugnaini E. 1998. Metabotropic glutamate receptors are associated with non-synaptic appendages of unipolar brush cells in rat cerebellar cortex and cochlear nuclear complex. J Neurocytol 27:303-317.
    • (1998) J Neurocytol , vol.27 , pp. 303-317
    • Jaarsma, D.1    Dino, M.R.2    Ohishi, H.3    Shigemoto, R.4    Mugnaini, E.5
  • 19
    • 0014671360 scopus 로고
    • Electron microscopy of synaptic glomeruli in the thalamic relay nuclei of the cat
    • Jones EG, Powell TPS. 1969. Electron microscopy of synaptic glomeruli in the thalamic relay nuclei of the cat. Proc R Soc Lond (Biol) 172:153-171.
    • (1969) Proc R Soc Lond (Biol) , vol.172 , pp. 153-171
    • Jones, E.G.1    Powell, T.P.S.2
  • 20
    • 0038741500 scopus 로고    scopus 로고
    • Differential expression of the glutamate transporter GLT-1 in the small cell shell of the chinchilla cochlear nucleus
    • Josephson EM, Morest DK. 1999. Differential expression of the glutamate transporter GLT-1 in the small cell shell of the chinchilla cochlear nucleus. Assoc Res Otolaryngol Abstr 265.
    • (1999) Assoc Res Otolaryngol Abstr , pp. 265
    • Josephson, E.M.1    Morest, D.K.2
  • 21
    • 0038741499 scopus 로고    scopus 로고
    • Synaptic nests of mouse cochlear nucleus are deficient in glutamate transporters
    • Josephson EM, Morest DK. 2000. Synaptic nests of mouse cochlear nucleus are deficient in glutamate transporters. Assoc Res Otolaryngol Abstr 387.
    • (2000) Assoc Res Otolaryngol Abstr , pp. 387
    • Josephson, E.M.1    Morest, D.K.2
  • 22
    • 0026458124 scopus 로고
    • Primary structure and functional characterization of a high-affinity glutamate transporter
    • Kanai Y, Hediger MA. 1992. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360: 467-471.
    • (1992) Nature , vol.360 , pp. 467-471
    • Kanai, Y.1    Hediger, M.A.2
  • 23
    • 0029586025 scopus 로고
    • Neuronal highaffinity glutamate transport in the rat central nervous system
    • Kanai Y, Bhide PG, Difiglia M, Hediger MA. 1995. Neuronal highaffinity glutamate transport in the rat central nervous system. NeuroReport 6:2357-2362.
    • (1995) NeuroReport , vol.6 , pp. 2357-2362
    • Kanai, Y.1    Bhide, P.G.2    Difiglia, M.3    Hediger, M.A.4
  • 24
    • 0015758518 scopus 로고
    • Octopus cells in the cochlear nucleus of the cat: Heterotypic synapses upon homeotypic neurons
    • Kane EC. 1973. Octopus cells in the cochlear nucleus of the cat: heterotypic synapses upon homeotypic neurons. Int J Neurosci 5:251-279.
    • (1973) Int J Neurosci , vol.5 , pp. 251-279
    • Kane, E.C.1
  • 25
    • 0016234583 scopus 로고
    • Synaptic organization in the dorsal cochlear nucleus of the cat: A light and electron microscopic study
    • Kane EC. 1974. Synaptic organization in the dorsal cochlear nucleus of the cat: a light and electron microscopic study. J Comp Neurol 155:301-330.
    • (1974) J Comp Neurol , vol.155 , pp. 301-330
    • Kane, E.C.1
  • 26
    • 0032194950 scopus 로고    scopus 로고
    • The number of glutamate transporter subtype molecules at glutamatergic synapses: Chemical and serological quantification in young adult rat brain
    • Lehre KP, Danbolt NC. 1998. The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and serological quantification in young adult rat brain. J Neurosci 18:8751-8757.
    • (1998) J Neurosci , vol.18 , pp. 8751-8757
    • Lehre, K.P.1    Danbolt, N.C.2
  • 27
    • 0028958939 scopus 로고
    • Differential expression of two glial glutamate transporters in the rat brain: Quantitative and immunocytochemical observations
    • Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC. 1995. Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci 15:1835-1853.
    • (1995) J Neurosci , vol.15 , pp. 1835-1853
    • Lehre, K.P.1    Levy, L.M.2    Ottersen, O.P.3    Storm-Mathisen, J.4    Danbolt, N.C.5
  • 28
    • 0014994539 scopus 로고
    • Dendrodendritic synapses of cells that have axons: The fine structure of the Golgi type II cell in the medial geniculate body of the cat
    • Morest DK. 1971. Dendrodendritic synapses of cells that have axons: the fine structure of the Golgi type II cell in the medial geniculate body of the cat. Z Anat Entwickl-Gesch 133:216-246.
    • (1971) Z Anat Entwickl-Gesch , vol.133 , pp. 216-246
    • Morest, D.K.1
  • 29
    • 0016592642 scopus 로고
    • Synaptic relationships of Golgi type II cells in the medial geniculate body of the cat
    • Morest DK. 1975. Synaptic relationships of Golgi type II cells in the medial geniculate body of the cat. J Comp Neurol 162:157-193.
    • (1975) J Comp Neurol , vol.162 , pp. 157-193
    • Morest, D.K.1
  • 30
    • 0038403382 scopus 로고    scopus 로고
    • Structural basis for signal processing. Challenge of the synaptic nests
    • Syka J, editor. New York: Plenum Press
    • Morest DK. 1997. Structural basis for signal processing. Challenge of the synaptic nests. In: Syka J, editor. Acoustical signal processing in the central auditory system. New York: Plenum Press. p 19-32.
    • (1997) Acoustical Signal Processing in the Central Auditory System , pp. 19-32
    • Morest, D.K.1
  • 31
    • 0035805092 scopus 로고    scopus 로고
    • Control of glutamate clearance and synaptic efficacy by glial coverage of neurons
    • Oliet SHR, Piet R, Poulain DA. 2001. Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science 292:923-926.
    • (2001) Science , vol.292 , pp. 923-926
    • Oliet, S.H.R.1    Piet, R.2    Poulain, D.A.3
  • 32
    • 0029915273 scopus 로고    scopus 로고
    • Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites
    • Otis TS, Wu Y-C, Trussell LO. 1996. Delayed clearance of transmitter and the role of glutamate transporters at synapses with multiple release sites. J Neurosci 16:1634-1644.
    • (1996) J Neurosci , vol.16 , pp. 1634-1644
    • Otis, T.S.1    Wu, Y.-C.2    Trussell, L.O.3
  • 33
    • 0013924086 scopus 로고
    • The morphology of laminae A and A1 of the dorsal nucleus of the lateral geniculate body of the cat
    • Peters A, Palay SL. 1966. The morphology of laminae A and A1 of the dorsal nucleus of the lateral geniculate body of the cat. J Anat 100:451-486.
    • (1966) J Anat , vol.100 , pp. 451-486
    • Peters, A.1    Palay, S.L.2
  • 34
    • 0029826840 scopus 로고    scopus 로고
    • Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localizations in the dorsal cochlear nucleus
    • Petralia RS, Wang Y-X, Zhao H-M, Wenthold RJ. 1996. Ionotropic and metabotropic glutamate receptors show unique postsynaptic, presynaptic, and glial localizations in the dorsal cochlear nucleus. J Comp Neurol 372:356-383.
    • (1996) J Comp Neurol , vol.372 , pp. 356-383
    • Petralia, R.S.1    Wang, Y.-X.2    Zhao, H.-M.3    Wenthold, R.J.4
  • 35
    • 0030809706 scopus 로고    scopus 로고
    • Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons
    • Petralia RS, Wang Y-X, Mayat E, Wenthold RJ. 1997. Glutamate receptor subunit 2-selective antibody shows a differential distribution of calcium-impermeable AMPA receptors among populations of neurons. J Comp Neurol 385:456-476.
    • (1997) J Comp Neurol , vol.385 , pp. 456-476
    • Petralia, R.S.1    Wang, Y.-X.2    Mayat, E.3    Wenthold, R.J.4
  • 37
    • 0000069901 scopus 로고
    • Identification of glutamatergic and aspartatergic pathways in the auditory system
    • Drescher D, editor. Springfield, IL: Thomas
    • Potashner SJ, Morest DK, Oliver DL, Jones DR. 1985. Identification of glutamatergic and aspartatergic pathways in the auditory system. In: Drescher D, editor. Auditory biochemistry. Springfield, IL: Thomas. p 141-162.
    • (1985) Auditory Biochemistry , pp. 141-162
    • Potashner, S.J.1    Morest, D.K.2    Oliver, D.L.3    Jones, D.R.4
  • 38
    • 0035869460 scopus 로고    scopus 로고
    • Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain
    • Rao VLR, Dogan A, Todd KG, Bowen KK, Kim B, Rothstein JD, Dempsey RJ. 2001. Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain. J Neurosci 21:1876-1883.
    • (2001) J Neurosci , vol.21 , pp. 1876-1883
    • Rao, V.L.R.1    Dogan, A.2    Todd, K.G.3    Bowen, K.K.4    Kim, B.5    Rothstein, J.D.6    Dempsey, R.J.7
  • 39
    • 0014085991 scopus 로고
    • Light and electron microscopic observations on the inner plexiform layer of the rabbit retina
    • Raviola G, Raviola E. 1967. Light and electron microscopic observations on the inner plexiform layer of the rabbit retina. Am J Anat 120:403-426.
    • (1967) Am J Anat , vol.120 , pp. 403-426
    • Raviola, G.1    Raviola, E.2
  • 42
    • 0032079863 scopus 로고    scopus 로고
    • Extrasynaptic glutamate diffusion in the hippocampus: Ultrastructural constraints, uptake, and receptor activation
    • Rusakov DA, Kullmann DM. 1998. Extrasynaptic glutamate diffusion in the hippocampus: Ultrastructural constraints, uptake, and receptor activation. J Neurosci 18:3158-3170.
    • (1998) J Neurosci , vol.18 , pp. 3158-3170
    • Rusakov, D.A.1    Kullmann, D.M.2
  • 43
    • 0033710845 scopus 로고    scopus 로고
    • Modulation of GABAergic signaling among interneurons by metabotropic glutamate receptors
    • Semyanov A, Kullmann DM. 2000. Modulation of GABAergic signaling among interneurons by metabotropic glutamate receptors. Neuron 25:663-672.
    • (2000) Neuron , vol.25 , pp. 663-672
    • Semyanov, A.1    Kullmann, D.M.2
  • 44
    • 0026489330 scopus 로고
    • Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain
    • Storck T, Schulte S, Hofmann K, Stoffel W. 1992. Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc Natl Acad Sci USA 89:10955-10959.
    • (1992) Proc Natl Acad Sci USA , vol.89 , pp. 10955-10959
    • Storck, T.1    Schulte, S.2    Hofmann, K.3    Stoffel, W.4
  • 45
    • 0032171045 scopus 로고    scopus 로고
    • Quantification of a neurotrophin receptor from submilligram quantities of brain tissue using Western blotting
    • Suneja SK, Potashner SJ. 1998. Quantification of a neurotrophin receptor from submilligram quantities of brain tissue using Western blotting. Brain Res Pros 3:88-93.
    • (1998) Brain Res Pros , vol.3 , pp. 88-93
    • Suneja, S.K.1    Potashner, S.J.2
  • 47
    • 0033566709 scopus 로고    scopus 로고
    • Three-dimensional relationships between hippocampal synapses and astrocytes
    • Ventura R, Harris KM. 1999. Three-dimensional relationships between hippocampal synapses and astrocytes. J Neurosci 19:6897-6906.
    • (1999) J Neurosci , vol.19 , pp. 6897-6906
    • Ventura, R.1    Harris, K.M.2
  • 48
    • 0029996642 scopus 로고    scopus 로고
    • Ultrastructural study of the granule cell domain of the cochlear nucleus in rats: Mossy fiber endings and their targets
    • Weedman DL, Pongstaporn T, Ryugo DK. 1996. Ultrastructural study of the granule cell domain of the cochlear nucleus in rats: mossy fiber endings and their targets. J Comp Neurol 369:345-360.
    • (1996) J Comp Neurol , vol.369 , pp. 345-360
    • Weedman, D.L.1    Pongstaporn, T.2    Ryugo, D.K.3
  • 49
    • 0007381397 scopus 로고
    • Glutamate and aspartate as neurotransmitters of the auditory nerve
    • Drescher D, editor. Springfield, IL Thomas
    • Wenthold RJ. 1985. Glutamate and aspartate as neurotransmitters of the auditory nerve. In: Drescher D, editor. Auditory biochemistry. Springfield, IL Thomas. p 125-140.
    • (1985) Auditory Biochemistry , pp. 125-140
    • Wenthold, R.J.1
  • 50
    • 0015502252 scopus 로고
    • Synaptic organization in the olfactory glomerulus of the mouse
    • White EL. 1972. Synaptic organization in the olfactory glomerulus of the mouse. Brain Res 37:69-80.
    • (1972) Brain Res , vol.37 , pp. 69-80
    • White, E.L.1
  • 51
    • 0030031980 scopus 로고    scopus 로고
    • Mossy fiber projections from the cuneate nucleus to the cochlear nucleus in the rat
    • Wright DD, Ryugo DK. 1996. Mossy fiber projections from the cuneate nucleus to the cochlear nucleus in the rat. J Comp Neurol 365:159-172.
    • (1996) J Comp Neurol , vol.365 , pp. 159-172
    • Wright, D.D.1    Ryugo, D.K.2
  • 52
    • 0035887859 scopus 로고    scopus 로고
    • Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in glutamate transporter and AMPA receptor expression
    • Zhou M, Kimelberg HK. 2001. Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in glutamate transporter and AMPA receptor expression. J Neurosci 21:7901-7908.
    • (2001) J Neurosci , vol.21 , pp. 7901-7908
    • Zhou, M.1    Kimelberg, H.K.2


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.