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The Structural Development of the Mouse Dorsal Cochlear Nucleus

  • Miaomiao Mao
  • Johanna M. Montgomery
  • M. Fabiana Kubke
  • Peter R. ThorneEmail author
Research Article

Abstract

The dorsal cochlear nucleus (DCN) is a major subdivision of the mammalian cochlear nucleus (CN) that is thought to be involved in sound localization in the vertical plane and in feature extraction of sound stimuli. The main principal cell type (pyramidal cells) integrates auditory and non-auditory inputs, which are considered to be important in performing sound localization tasks. This study aimed to investigate the histological development of the CD-1 mouse DCN, focussing on the postnatal period spanning the onset of hearing (P12). Fluorescent Nissl staining revealed that the three layers of the DCN were identifiable as early as P6 with subsequent expansion of all layers with age. Significant increases in the size of pyramidal and cartwheel cells were observed between birth and P12. Immunohistochemistry showed substantial changes in synaptic distribution during the first two postnatal weeks with subsequent maturation of the presumed mossy fibre terminals. In addition, GFAP immunolabelling identified several glial cell types in the DCN including the observation of putative tanycytes for the first time. Each glial cell type had specific spatial and temporal patterns of maturation with apparent rapid development during the first two postnatal weeks but little change thereafter. The rapid maturation of the structural organization and DCN components prior to the onset of hearing possibly reflects an influence from spontaneous activity originating in the cochlea/auditory nerve. Further refinement of these connections and development of the non-auditory connections may result from the arrival of acoustic input and experience dependent mechanisms.

Keywords

cochlear nucleus dorsal cochlear nucleus auditory brainstem postnatal development mouse 

Notes

Acknowledgments

This research was published as part of a PhD thesis by M Mao and was supported by a University of Auckland Doctoral Scholarship, an Auckland Medical Research Foundation Senior Scholarship and a University of Auckland School of Medical Sciences writing scholarship.

Conflict of Interest

The authors declare no conflict of interest.

References

  1. Aldahmash A, Atteya M (2011) Ganglionectomy in the adult male rat increases neuronal size and synaptic density in remaining contralateral major pelvic ganglion. Curr Neurobiol 2:5–15Google Scholar
  2. Angulo A, Merchán JA, Merchán MA (1990) Morphology of the rat cochlear primary afferents during prenatal development: a Cajal’s reduced silver and rapid Golgi study. J Anat 168:241–255PubMedCentralPubMedGoogle Scholar
  3. Apostolides PF, Trussell LO (2014) Superficial stellate cells of the dorsal cochlear nucleus. Front Neural Circuits 8:63PubMedCentralPubMedCrossRefGoogle Scholar
  4. Bartolomé MV, Ibáñez MA, López-Sánchez JG, Merchán-Pérez A, Gil-Loyzaga P (1993) Synaptophysin immunoreactivity in the cochlear nuclei of mammals: a comparative study. ORL J Otorhinolaryngol Relat Spec 55:317–321PubMedCrossRefGoogle Scholar
  5. Baxter KK, Uittenbogaard M, Yoon J, Chiaramello A (2009) The neurogenic basic helix–loop–helix transcription factor NeuroD6 concomitantly increases mitochondrial mass and regulates cytoskeletal organization in the early stages of neuronal differentiation. ASN Neuro 1:195–211CrossRefGoogle Scholar
  6. Benson TE, Brown MC (2004) Postsynaptic targets of type II auditory nerve fibers in the cochlear nucleus. J Assoc Res Otolaryngol 5:111–125PubMedCentralPubMedCrossRefGoogle Scholar
  7. Berglund AM, Brown MC (1994) Central trajectories of type II spiral ganglion cells from various cochlear regions in mice. Hear Res 75:121PubMedCrossRefGoogle Scholar
  8. Berglund AM, Benson TE, Brown MC (1996) Synapses from labeled type II axons in the mouse cochlear nucleus. Hear Res 94:31–46PubMedCrossRefGoogle Scholar
  9. Berrebi AS, Mugnaini E (1991) Distribution and targets of the cartwheel cell axon in the dorsal cochlear nucleus of the guinea pig. Anat Embryol 183:427–454PubMedCrossRefGoogle Scholar
  10. Brugge JF (1983) Development of the lower brainstem auditory nuclei. In: Development of auditory and vestibular systems. Academic Press, INC., New York, pp. 89–120Google Scholar
  11. Cant NB (1992) The cochlear nucleus: neuronal types and their synaptic organization. In: Webster DB, Popper AN, Fay RR (eds) The mammalian auditory pathway: neuroanatomy. New York, Springer-Verlag, pp 66–116CrossRefGoogle Scholar
  12. Cant NB (1997) Structural development of the mammalian central auditory pathways. In: Rubel EW, Popper AN, Fay RR (eds) Development of the auditory system. New York, Springer-Verlag, pp 315–414Google Scholar
  13. Caspary DM, Schatteman TA, Hughes LF (2005) Age-related changes in the inhibitory response properties of dorsal cochlear nucleus output neurons: role of inhibitory inputs. J Neurosci 25:10952–10959PubMedCrossRefGoogle Scholar
  14. Dehmel S, Pradhan S, Koehler S, Bledsoe S, Shore S (2012) Noise overexposure alters long-term somatosensory-auditory processing in the dorsal cochlear nucleus—Possible basis for tinnitus-related hyperactivity? J Neurosci 32:1660–1671PubMedCentralPubMedCrossRefGoogle Scholar
  15. Diño MR, Mugnaini E (2008) Distribution and phenotypes of unipolar brush cells in relation to the granule cell system of the rat cochlear nucleus. Neuroscience 154:29–50PubMedCentralPubMedCrossRefGoogle Scholar
  16. Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214PubMedCrossRefGoogle Scholar
  17. Eng LF, Ghirnikar RS (1994) GFAP and Astrogliosis. Brain Pathol 4:229–237PubMedCrossRefGoogle Scholar
  18. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451PubMedCrossRefGoogle Scholar
  19. Fariñas I, Jones KR, Tessarollo L, Vigers AJ, Huang E, Kirstein M, de Caprona DC, Coppola V, Backus C, Reichardt LF et al (2001) Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression. J Neurosci 21:6170–6180PubMedCentralPubMedGoogle Scholar
  20. Felten DL, Cummings JP, Burnett BT (1981) Ontogeny of caudal fourth ventricular tanycytes in the rabbit brain: A Golgi study. Anat Rec 200:321–330Google Scholar
  21. Gil-Loyzaga P, Bartolome M, Ibanez A (1998) Synaptophysin immunoreactivity in the cat cochlear nuclei. Histol Histopathol 13:415–424PubMedGoogle Scholar
  22. Hackney CM, Osen KK, Kolston J (1990) Anatomy of the cochlear nuclear complex of guinea pig. Anat Embryol (Berl) 182:123–149CrossRefGoogle Scholar
  23. Haenggeli C-A, Pongstaporn T, Doucet JR, Ryugo DK (2005) Projections from the spinal trigeminal nucleus to the cochlear nucleus in the rat. J Comp Neurol 484:191–205PubMedCrossRefGoogle Scholar
  24. Harris JA, Rubel EW (2006) Afferent regulation of neuron number in the cochlear nucleus: cellular and molecular analyses of a critical period. Hear Res 216–217:127–137PubMedCrossRefGoogle Scholar
  25. Irie T, Fukui I, Ohmori H (2006) Activation of GIRK channels by muscarinic receptors and group II metabotropic glutamate receptors suppresses Golgi cell activity in the cochlear nucleus of mice. J Neurophysiol 96:2633–2644PubMedCrossRefGoogle Scholar
  26. Ivanova A, Yuasa S (1998) Neuronal migration and differentiation in the development of the mouse dorsal cochlear nucleus. Dev Neurosci 20:495–511PubMedCrossRefGoogle Scholar
  27. Jansson LC, Louhivuori L, Wigren H-K, Nordström T, Louhivuori V, Castrén ML, Åkerman KE (2013) Effect of glutamate receptor antagonists on migrating neural progenitor cells. Eur J Neurosci 37:1369–1382PubMedCrossRefGoogle Scholar
  28. Kane ES, Habib CP (1978) Development of the dorsal cochlear nucleus of the cat: an electron microscopic study. J Anat 153:321–343CrossRefGoogle Scholar
  29. Koehler SD, Shore SE (2013) Stimulus-timing dependent multisensory plasticity in the guinea pig dorsal cochlear nucleus. PLoS One 8:e59828PubMedCentralPubMedCrossRefGoogle Scholar
  30. Koehler SD, Pradhan S, Manis PB, Shore SE (2011) Somatosensory inputs modify auditory spike timing in dorsal cochlear nucleus principal cells. Eur J Neurosci 33:409–420PubMedCentralPubMedCrossRefGoogle Scholar
  31. Koundakjian EJ, Appler JL, Goodrich LV (2007) Auditory neurons make stereotyped wiring decisions before maturation of their targets. J Neurosci 27:14078–14088PubMedCrossRefGoogle Scholar
  32. Lee JH, Kim HJ, Suh M-W, Ahn SC (2011) Sustained Fos expression is observed in the developing brainstem auditory circuits of kanamycin-treated rats. Neurosci Lett 505:98–103PubMedCrossRefGoogle Scholar
  33. Limb CJ, Ryugo DK (2000) Development of primary axosomatic endings in the anteroventral cochlear nucleus of mice. J Assoc Res Otolaryngol 1:103–119PubMedCentralPubMedCrossRefGoogle Scholar
  34. Luoma JI, Zirpel L (2008) Deafferentation-induced activation of NFAT (nuclear factor of activated T-cells) in cochlear nucleus neurons during a developmental critical period: a role for NFATc4-dependent apoptosis in the CNS. J Neurosci 28:3159–3169PubMedCrossRefGoogle Scholar
  35. Mahendrasingam S, MacDonald JA, Furness DN (2011) Relative time course of degeneration of different cochlear structures in the CD/1 mouse model of accelerated aging. JARO 12:437–453PubMedCentralPubMedCrossRefGoogle Scholar
  36. Malhotra SK, Shnitka TK, Elbrink J (1989) Reactive astrocytes–a review. Cytobios 61:133–160Google Scholar
  37. Manderson C (2010) Onset of hearing in the mouse. Master of audiology thesis (unpublished). University of AucklandGoogle Scholar
  38. Mao M (2013) The structural, molecular and functional development of the dorsal cochlear nucleus. PhD thesis. University of AucklandGoogle Scholar
  39. Martin MR, Rickets C (1981) Histogenesis of the cochlear nucleus of the mouse. J Comp Neurol 197:169–184PubMedCrossRefGoogle Scholar
  40. May BJ (2000) Role of the dorsal cochlear nucleus in the sound localization behavior of cats. Hear Res 148:74–87PubMedCrossRefGoogle Scholar
  41. McClure MM, Threlkeld SW, Rosen GD, Fitch RH (2006) Rapid auditory processing and learning deficits in rats with P1 versus P7 neonatal hypoxic-ischemic injury. Behav Brain Res 172:114–121PubMedCentralPubMedCrossRefGoogle Scholar
  42. Micheva KD, Busse B, Weiler NC, O’Rourke N, Smith SJ (2010) Single-synapse analysis of a diverse synapse population: proteomic imaging methods and markers. Neuron 68:639–653PubMedCentralPubMedCrossRefGoogle Scholar
  43. Middleton JW, Kiritani T, Pedersen C, Turner JG, Shepherd GMG, Tzounopoulos T (2011) Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. Proc Natl Acad Sci U S A 108:7601–7606PubMedCentralPubMedCrossRefGoogle Scholar
  44. Mlonyeni M (1967) The late stages of the development of the primary cochlear nuclei in mice. Brain Res 4:334–344PubMedCrossRefGoogle Scholar
  45. Mugnaini E, Warr WB, Osen KK (1980a) Distribution and light microscopic features of granule cells in the cochlear nuclei of cat, rat, and mouse. J Comp Neurol 191:581–606PubMedCrossRefGoogle Scholar
  46. Mugnaini E, Osen KK, Dahl AL, Friedrich VL, Korte G (1980b) Fine structure of granule cells and related interneurons (termed Golgi cells) in the cochlear nuclear complex of cat, rat and mouse. J Neurocytol 9:537–570PubMedCrossRefGoogle Scholar
  47. Nagy JI, Rash JE (2000) Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Res Rev 32:29–44PubMedCrossRefGoogle Scholar
  48. Parham K, Kim DO (1995) Spontaneous and sound-evoked discharge characteristics of complex-spiking neurons in the dorsal cochlear nucleus of the unanesthetized decerebrate cat. J Neurophysiol 73:550–561PubMedGoogle Scholar
  49. Pasic TR, Rubel EW (1989) Rapid changes in gerbil anteroventral cochlear nucleus cell size following blockade auditory nerve electrical activity in gerbils. J Comp Neurol 283:474–480PubMedCrossRefGoogle Scholar
  50. Pasic TR, Rubel EW (1991) Cochlear nucleus cell size is regulated by auditory nerve electrical activity. Otolaryngol Head Neck Surg 104:6–13PubMedGoogle Scholar
  51. Pierce ET (1967) Histogenesis of the dorsal and ventral cochlear nuclei in the mouse. An autoradiographic study. J Comp Neurol 131:27–54PubMedCrossRefGoogle Scholar
  52. Romand R, Romand M-R (1985) Qualitative and quantitative observations of spiral ganglion development in the rat. Hear Res 18:111–120PubMedCrossRefGoogle Scholar
  53. Schatteman TA, Hughes LF, Caspary DM (2008) Aged-related loss of temporal processing: altered responses to amplitude modulated tones in rat dorsal cochlear nucleus. Neuroscience 154:329–337PubMedCentralPubMedCrossRefGoogle Scholar
  54. Schweitzer L (1990) Differentiation of apical, basal and mixed dendrites of fusiform cells in the cochlear nucleus. Brain Res Dev Brain Res 56:19–27PubMedCrossRefGoogle Scholar
  55. Schweitzer L, Cant NB (1984) Development of the cochlear innervation of the dorsal cochlear nucleus of the hamster. J Comp Neurol 225:228–243PubMedCrossRefGoogle Scholar
  56. Schweitzer L, Cant NB (1985) Differentiation of the giant and fusiform cells in the dorsal cochlear nucleus of the hamster. Brain Res 352:69–82PubMedCrossRefGoogle Scholar
  57. Schweitzer L, Cecil T (1992) Morphology of HRP-labelled cochlear nerve axons in the dorsal cochlear nucleus of the developing hamster. Hear Res 60:34–44PubMedCrossRefGoogle Scholar
  58. Shehab SAS, Cronly-Dillon JR, Nona SN, Stafford CA (1990) Preferential histochemical staining of protoplasmic and fibrous astrocytes in rat CNS with GFAP antibodies using different fixatives. Brain Res 518:347–352PubMedCrossRefGoogle Scholar
  59. Shore SE, Zhou J (2006) Somatosensory influence on the cochlear nucleus and beyond. Hear Res 216:90–99PubMedCrossRefGoogle Scholar
  60. Song L, McGee J, Walsh EJ (2006) Frequency- and level-dependent changes in auditory brainstem responses (ABRs) in developing mice. JASA 119:2242CrossRefGoogle Scholar
  61. Tritsch NX, Bergles DE (2010) Developmental regulation of spontaneous activity in the mammalian cochlea. J Neurosci 30:1539–1550PubMedCentralPubMedCrossRefGoogle Scholar
  62. Tritsch NX, Yi E, Gale JE, Glowatzki E, Bergles DE (2007) The origin of spontaneous activity in the developing auditory system. Nature 450:50–55PubMedCrossRefGoogle Scholar
  63. Walton JP (2010) Timing is everything: temporal processing deficits in the aged auditory brainstem. Hear Res 264:63–69PubMedCrossRefGoogle Scholar
  64. Wang H, Turner JG, Ling L, Parrish JL, Hughes LF, Caspary DM (2009) Age-related changes in glycine receptor subunit composition and binding in dorsal cochlear nucleus. Neuroscience 160:227–239PubMedCentralPubMedCrossRefGoogle Scholar
  65. Webster DB (1983) A critical period during postnatal auditory development of mice. Int J Pediatr Otorhinolaryngol 6:107–118PubMedCrossRefGoogle Scholar
  66. Webster DB (1988) Conductive hearing loss affects the growth of the cochlear nuclei over an extended period of time. Hear Res 32:185–192PubMedCrossRefGoogle Scholar
  67. Webster DB, Trune DR (1982) Cochlear nuclear complex of mice. Am J Anat 163:103–130PubMedCrossRefGoogle Scholar
  68. Webster DB, Webster M (1980) Mouse brainstem auditory nuclei development. Ann Otol Rhinol Laryngol Suppl 89:254–256PubMedGoogle Scholar
  69. Willard FH (1993) Postnatal development of auditory nerve projections to the cochlear nucleus in monodelphis domestica. In: The mammalian cochlear nuclei: organization and function, p. 29Google Scholar
  70. Young ED, Oertel D (2004) Cochlear nucleus. In: Shepherd GM (ed) The synaptic organization of the brain. Oxford University Press, New YorkGoogle Scholar
  71. Zhang S, Oertel D (1993) Cartwheel and superficial stellate cells of the dorsal cochlear nucleus of mice: intracellular recordings in slices. J Neurophysiol 69:1384–1397PubMedGoogle Scholar
  72. Zhang S, Oertel D (1994) Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells. J Neurophysiol 71:914–930PubMedGoogle Scholar
  73. Zhou J, Shore S (2004) Projections from the trigeminal nuclear complex to the cochlear nuclei: a retrograde and anterograde tracing study in the guinea pig. J Neurosci Res 78:901–907PubMedCrossRefGoogle Scholar
  74. Zhou J, Nannapaneni N, Shore S (2007) Vessicular glutamate transporters 1 and 2 are differentially associated with auditory nerve and spinal trigeminal inputs to the cochlear nucleus. J Comp Neurol 500:777–787PubMedCrossRefGoogle Scholar

Copyright information

© Association for Research in Otolaryngology 2015

Authors and Affiliations

  • Miaomiao Mao
    • 1
    • 4
  • Johanna M. Montgomery
    • 1
    • 4
  • M. Fabiana Kubke
    • 2
    • 4
  • Peter R. Thorne
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Physiology, School of Medical Sciences, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  2. 2.Department of Anatomy and Radiology, School of Medical Sciences, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  3. 3.Section of Audiology, School of Population Health, Faculty of Medical and Health SciencesUniversity of AucklandAucklandNew Zealand
  4. 4.Centre for Brain ResearchUniversity of AucklandAucklandNew Zealand

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