Abstract
In mammals, the superior olivary complex (SOC) of the brainstem is composed of nuclei that integrate afferent auditory originating from both ears. Here, the expression of different calcium-binding proteins in subnuclei of the SOC was studied in distantly related mammals, the Mongolian gerbil (Meriones unguiculatus) and the gray short-tailed opossum (Monodelphis domestica) to get a better understanding of the basal nuclear organization of the SOC. Combined immunofluorescence labeling of the calcium-binding proteins (CaBPs) parvalbumin, calbindin-D28k, and calretinin as well as pan-neuronal markers displayed characteristic distribution patterns highlighting details of neuronal architecture of SOC nuclei. Parvalbumin was found in almost all neurons of SOC nuclei in both species, while calbindin and calretinin were restricted to specific cell types and axonal terminal fields. In both species, calbindin displayed a ubiquitous and mostly selective distribution in neurons of the medial nucleus of trapezoid body (MNTB) including their terminal axonal fields in different SOC targets. In Meriones, calretinin and calbindin showed non-overlapping expression patterns in neuron somata and terminal fields throughout the SOC. In Monodelphis, co-expression of calbindin and calretinin was observed in the MNTB, and hence both CaBPs were also co-localized in terminal fields within the adjacent SOC nuclei. The distribution patterns of CaBPs in both species are discussed with respect to the intrinsic neuronal SOC circuits as part of the auditory brainstem system that underlie the binaural integrative processing of acoustic signals as the basis for localization and discrimination of auditory objects.
Similar content being viewed by others
References
Adams JC, Mugnaini E (1990) Immunocytochemical evidence for inhibitory and disinhibitory circuits in the superior olive. Hear Res 49:281–298
Ahlfeld J, Mustari M, Horn AK (2011) Sources of calretinin inputs to motoneurons of extraocular muscles involved in upgaze. Ann N Y Acad Sci 1233:91–99
Aitkin L (1996) The anatomy of the cochlear nuclei and superior olivary complex of arboreal australian marsupials. Brain Behav Evol 48:103–114
Aitkin LM, Byers M, Nelson JE (1986) Brain stem auditory nuclei and their connections in a carnivorous marsupial, the northern native cat (Dasyurus hallucatus). Brain Behav Evol 29:1–16
Aitkin L, Cochran S, Frost S, Martsi-McClintock A, Masterton B (1997) Features of the auditory development of the short-tailed Brazilian opossum, Monodelphis domestica: evoked responses, neonatal vocalizations and synapses in the inferior colliculus. Hear Res 113:69–75
Andressen C, Blümcke I, Celio MR (1993) Calcium-binding proteins: selective markers of nerve cells. Cell Tissue Res 271:181–208
Baimbridge KG, Celio MR, Rogers JH (1992) Calcium-binding proteins in the nervous system. Trends Neurosci 15:303–308
Banks MI, Smith PH (1992) Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body. J Neurosci 12:2819–2837
Barnes-Davies M, Barker MC, Osmani F, Forsythe ID (2004) Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive. Eur J Neurosci 19:325–333
Bazwinsky I, Hilbig H, Bidmon H-J, Rübsamen R (2003) Characterization of the human superior olivary complex by calcium binding proteins and neurofilament H (SMI-32). J Comp Neurol 456:292–303
Bazwinsky I, Bidmon H-J, Zilles K, Hilbig H (2005) Characterization of the rhesus monkey superior olivary complex by calcium binding proteins and synaptophysin. J Anat 207:745–761
Bazwinsky I, Härtig W, Rübsamen R (2008) Characterization of cochlear nucleus principal cells of Meriones unguiculatus and Monodelphis domestica by use of calcium-binding protein immunolabeling. J Chem Neuroanat 35:158–174
Caicedo A, d’Aldin C, Puel JL, Eybalin M (1996) Distribution of calcium binding protein immunoreactivities in the guinea pig auditory brainstem. Anat Embryol 194:465–478
Cant NB (1984) The fine structure of the lateral superior olivary nucleus of the cat. J Comp Neurol 227:63–77
Cant NB (1991) Projections to the lateral and medial superior olivary nuclei from the spherical and globular bushy cells of the anteroventral cochlear nucleus. In: Altschuler RA, Bobbin RP, Clopton BM, Hoffmann DW (eds) Neurobiology of hearing: the central auditory system. Raven Press, New York, pp 99–119
Cant NB, Benson CG (2003) Parallel auditory pathways: projection patterns of the different neuronal populations in the dorsal and ventral cochlear nuclei. Brain Res Bull 60:457–474
Cant NB, Casseday JH (1986) Projections from the anteroventral cochlear nucleus to the lateral and medial superior olivary nuclei. J Comp Neurol 247:457–476
Cant NB, Hyson RL (1992) Projections from the lateral nucleus of the trapezoid body to the medial superior olivary nucleus in the gerbil. Hear Res 58:26–34
Carr CE (1986) Time coding in the electric fish and barn owls. Brain Behav Evol 28:122–133
Celio MR, Baier W, Schärer L, de Viragh PA, Gerday CH (1988) Monoclonal antibodies directed against the calcium binding protein parvalbumin. Cell Calcium 9:81–86
Celio MR, Baier W, Schärer L, Gregersen HJ, de Viragh PA, Norman AW (1990) Monoclonal antibodies directed against the calcium binding protein calbindin D-28k. Cell Calcium 11:599–602
Couchman K, Grothe B, Felmy F (2012) Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive. J Neurophysiol 107:1186–1198
Englitz B, Tolnai S, Typlt M, Kopp-Scheinpflug C, Jost J, Rübsamen R (2009) Reliability of Signal transmission at the giant synapses of Held in vivo. PLoS One 4:e7014
Felmy F, Schneggenburger R (2004) Developmental expression of the Ca2+-binding proteins calretinin and parvalbumin at the calyx of held of rats and mice. Eur J Neurosci 20:1473–1482
Finlayson PG, Caspary DM (1991) Low-frequency neurons in the lateral superior olive exhibit phase-sensitive binaural inhibition. J Neurophysiol 65:598–605
Fredrich M, Reisch A, Illing RB (2009) Neuronal subtype identity in the rat auditory brainstem as defined by molecular profile and axonal projection. Exp Brain Res 195:241–260
Friauf E (1993) Transient Appearance of Calbindin-D28k-positive neurons in the superior olivary complex of developing rats. J Comp Neurol 334:59–74
Friauf E (1994) Distribution of calcium-binding protein calbindin-D28k in the auditory system of adult and developing rats. J Comp Neurol 349:193–211
Frisina RD, Zettel ML, Kelley PE, Walton JP (1995) Distribution of calbindin D-28k immunoreactivity in the cochlear nucleus of the young adult chinchilla. Hear Res 85:53–68
Frost SB, Masterton RB (1994) Hearing in primitive mammals: Monodelphis domestica and Marmosa elegans. Hear Res 76:67–72
Gallyas F, Wolff JR, Böttcher H, Záborszky L (1980) A reliable method for demonstrating axonal degeneration shortly after axotomy. Stain Technol 55:291–297
Gibb R, Kolb B (1998) A method for vibratome sectioning of Golgi–Cox stained whole rat brain. J Neurosci Methods 79:1–4
Glaser EM, Van der Loos H (1981) Analysis of thick brain sections by obverse-reverse computer microscopy: application of a new, high clarity Golgi–Nissl stain. J Neurosci Methods 4:117–125
Glendenning KK, Masterton RB (1998) Comparative morphometry of mammalian central auditory systems: variation in nuclei and form of the ascending system. Brain Behav Evol 51:59–89
Glendenning KK, Brunso-Bechtold JK, Thompson GC, Masterton RB (1981) Ascending auditory afferents to the nuclei of the lateral lemniscus. J Comp Neurol 197:673–703
Glendenning KK, Hutson KA, Nudo RJ, Masterton RB (1985) Acoustic chiasm II: Anatomical basis of binaurality in lateral superior olive of cat. J Comp Neurol 232:261–285
Glendenning KK, Masterton RB, Baker BN, Wenthold RJ (1991) Acoustic chiasm III: nature, distribution, and sources of afferents to the lateral superior olive in the cat. J Comp Neurol 310:377–400
Grothe B (2000) The evolution of temporal processing in the medial superior olive, an auditory brainstem structure. Prog Neurobiol 61:581–610
Grothe B (2003) New roles for synaptic inhibition in sound localization. Nat Rev Neurosci 4:540–550
Grothe B, Pecka M (2014) The natural history of sound localization in mammals—a story of neuronal inhibition. Front Neural Circuits 8:116
Grothe B, Pecka M, McAlpine D (2010) Mechanisms of sound localization in mammals. Physiol Rev 90:983–1012
Guinan JJ Jr, Guinan SS, Norris BE (1972a) Single auditory units in the olivary complex I. Responses to sounds and classifications based on physiological properties. Int J Neurosci 4:101–120
Guinan JJ Jr, Norris BE, Guinan SS (1972b) Single auditory units in the olivary complex II. Superior olivary complex II: location of unit categories and tonotopic organization. Int J Neurosci 4:147–166
Heizmann CW, Braun K (1995) Calcium regulation by calcium-binding proteins in neurodegenerative disorders. Springer, Heidelberg
Helfert RH, Schwartz IR (1987) Morphological features of five neuronal classes in the gerbil lateral superior olive. Am J Anat 179:55–69
Johnston J, Forsythe ID, Kopp-Scheinpflug C (2010) Going native: voltage-gated potassium channels controlling neuronal excitability. J Physiol 588:3187–3200
Kägi U, Berchtold MW, Heizmann CW (1987) Ca2+-binding parvalbumin in rat testis. J Biol Chem 262:7314–7320
Kandler K, Friauf E (1995) Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats. J Neurosci 15:6890–6904
Kandler K, Clause A, Noh J (2009) Tonotopic reorganization of developing auditory brainstem circuits. Nat Neurosci 12:711–717
Keast A (1977) Historical biogeography of the marsupials. In: Stonehouse G, Gilmore D (eds) The biology of marsupials. Mac-Millan, London, pp 69–95
Kelley PE, Frisina RD, Zettel ML, Walton JP (1992) Differential calbindin-like immunoreactivity in the brain stem auditory system of the chinchilla. J Comp Neurol 319:196–212
Kevetter GA, Leonard RB (1997) Use of calcium-binding proteins to map inputs in vestibular nuclei of the gerbil. J Comp Neurol 386:317–327
Kil J, Kageyama GH, Semple MN, Kitzes LM (1995) Development of ventral cochlear nucleus projections to the superior olivary complex in gerbil. J Comp Neurol 353:317–340
Korada S, Schwartz IR (2000) Calcium binding proteins and the AMPA glutamate receptor subunits in gerbil cochlear nucleus. Hear Res 140:23–37
Kulesza RJ Jr (2014) Characterization of human auditory brainstem circuits by calcium-binding protein immunohistochemistry. Neuroscience 258:318–331
Kulesza RJ Jr, Kadner A, Berrebi AS (2007) Distinct roles for glycine and GABA in shaping the response properties of neurons in the superior paraolivary nucleus of the rat. J Neurophysiol 97:1610–1620
Kuwabara N, DiCaprio RA, Zook JM (1991) Afferents to the medial nucleus of the trapezoid body and their collateral projections. J Comp Neurol 314:684–706
Lohmann C, Friauf E (1996) Distribution of the calcium-binding proteins parvalbumin and calretinin in the auditory brainstem of adult and developing rats. J Comp Neurol 367:90–109
Marangos PJ, Schmechel DE (1987) Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci 10:269–295
Matsubara JA (1990) Calbindin D-28k immunoreactivity in the cat’s superior olivary complex. Brain Res 508:353–357
McAlpine D, Grothe B (2003) Sound localization and delay lines-do mammals fit the model? Trends Neurosci 26:347–350
Morest DK (1968a) The collateral system of the medial nucleus of the trapezoid body of the cat, its neuronal architecture and relation to the olivo-cochlear bundle. Brain Res 9:288–311
Morest DK (1968b) The growth of synaptic endings in the mammalian brain: a study of the calyces of the trapezoid body. Brain Res 127:201–220
Morest DK, Winer JA (1986) The comparative anatomy of neurons: homologous neurons in the medial geniculate body of the opossum and the cat. Adv Anat Embryol Cell Biol 97:1–96
Myoga MH, Lehnert S, Leibold C, Felmy F, Grothe B (2014) Glycinergic inhibition tunes coincidence detection in the auditory brainstem. Nat Commun 5:3790
Oertel D (1999) The role of timing in the brain stem auditory of developing auditory brainstem circuits. Nat Neurosci 12:711–717
Osen KK (1969) Cytoarchitecture of the cochlear nuclei in the cat. J Comp Neurol 136:453–484
Perkins GA, Jackson DR, Spirou GA (2015) Resolving presynaptic structure by electron tomography. Synapse 69:268–282
Reimer K (1995) Hearing in the marsupial Monodelphis domestica as determined by auditory-evoked brainstem responses. Audiology 34:334–342
Rogers JH (1987) Calretinin: a gene for a novel calcium-binding protein expressed principally in neurons. J Cell Biol 105:1343–1353
Rothman JS, Manis PB (2003) The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J Neurophysiol 89:3097–3113
Rowe M (1990) Organization of the cerebral cortex in monotremes and marsupials. In: Jones EG, Peters A (eds) cerebral cortex, vol 8B., Comparative structure and evolution of cerebral cortexPlenum Press, New York, pp 263–334
Sanes DH, Merickel M, Rubel EW (1989) Evidence for an alteration of the tonotopic map in the gerbil cochlea during development. J Comp Neurol 279:436–444
Sanes DH, Goldstein NA, Ostad M, Hillman DE (1990) Dendritic morphology of central auditory neurons correlates with their tonotopic position. J Comp Neurol 294(443–444):5
Schmidt H (2012) Three functional facets of calbindin D-28k. Front Mol Neurosci 5:25
Schneggenburger R, Forsythe ID (2006) The calyx of Held. Cell Tissue Res 326:311–337
Schofield BR (1994) Projections to the cochlear nuclei from principal cells in the medial nucleus of the trapezoid body in guinea pigs. J Comp Neurol 344:83–100
Schwaller B (2012) The use of transgenic mouse models to reveal the functions of Ca(2+) buffer proteins in excitable cells. Biochim Biophys Acta 1820:1294–1303
Schwaller B, Buchwald P, Blümcke I, Celio MR, Hunziker W (1993) Characterization of a polyclonal antiserum against the purified human recombinant calcium binding protein calretinin. Cell Calcium 14:639–648
Schwaller B, Brückner G, Celio MR, Härtig W (1999) A polyclonal goat antiserum against the calcium-binding protein calretinin is a versatile tool for various immunochemical techniques. J Neurosci Methods 92:137–144
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, New York, pp 66–116
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
Sonntag M, Englitz B, Typlt M, Rübsamen R (2011) The calyx of Held develops adult-like dynamics and reliability by hearing onset in the mouse in vivo. J Neurosci 31:6699–6709
Spangler KM, Warr WB, Henkel CK (1985) The projections of the principal cells of the medial nucleus of the trapezoid body in the cat. J Comp Neurol 238:249–262
Svirskis G, Kotak V, Sanes DH, Rinzel J (2002) Enhancement of signal-to-noise ratio and phase locking for small inputs by a low-threshold outward current in auditory neurons. J Neurosci 22:11019–11025
Takahashi TT, Carr CE, Brecha N, Konishi M (1987) Calcium binding protein-like immunoreactivity labels the terminal field of nucleus laminaris of the barn owl. J Neurosci 7:1843–1856
Thompson AM, Schofield BR (2000) Afferent projections of the superior olivary complex. Microsc Res Tech 51:330–354
Thompson RJ, Doran JF, Jackson P, Dhillon AP, Rhode J (1983) PGP 9.5—a new marker for vertebrate neurons and neuroendocrine cells. Brain Res 278:224–228
Tinner R, Oertle M, Heizmann CW, Bosshard HR (1990) Ca2+-binding site of carp parvalbumin recognized by monoclonal antibody. Cell Calcium 11:19–23
Tollin DJ (2003) The lateral superior olive: a functional role in sound source localization. Neuroscientist 9:127–143
Tollin DJ, Yin TC (2005) Interaural phase and level difference sensitivity in low-frequency neurons in the lateral superior olive. J Neurosci 25:10648–10657
Tsuchitani C (1997) Input from the medial nucleus of trapezoid body to an interaural level detector. Hear Res 105:211–224
Vater M, Braun K (1994) Parvalbumin, calbindin D-28k, and calretinin immunoreactivity in the ascending auditory pathway of horseshoe bats. J Comp Neurol 341:534–558
Warr WB (1966) Fiber degeneration following lesions in the anterior ventral cochlear nucleus of the cat. Exp Neurol 14:453–474
Webster WR, Batini C, Buisseret-Delmas C, Compoint C, Guegan M, Thomasset M (1990) Colocalization of calbindin and GABA in medial nucleus of the trapezoid body of the rat. Neurosci Lett 111:252–257
Willard FH, Martin GF (1983) The auditory brainstem nuclei and some of their projections to the inferior colliculus in the North American opossum. Neuroscience 10:1203–1232
Willard FH, Martin GF (1984) Collateral innervation of the inferior colliculus in the North American opossum: a study using fluorescent markers in a double-labeling paradigm. Brain Res 303:171–182
Winsky L, Nakata H, Martin BM, Jacobowitz DM (1989) Isolation, partial amino acid sequence, and immunohistochemical localization of a brain-specific calcium-binding protein. Proc Natl Acad Sci USA 86:10139–10143
Yavuzoglu A, Schofield BR, Wenstrup JJ (2010) Substrates of auditory frequency integration in a nucleus of the lateral lemniscus. Neuroscience 169:906–919
Zettel ML, Carr CE, O’Neill WE (1991) Calbindin-like immunoreactivity in the central auditory system of the mustached bat, Pteronotus parnelli. J Comp Neurol 313:1–16
Zook JM, DiCaprio RA (1988) Intracellular labeling of afferents to the lateral superior olive in the bat, Eptesicus fuscus. Hear Res 34:141–147
Acknowledgments
The study was supported by DFG RU 390/20-1 (Priority Program 1608) and DFG GRK 250/1-96.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bazwinsky-Wutschke, I., Härtig, W., Kretzschmar, R. et al. Differential morphology of the superior olivary complex of Meriones unguiculatus and Monodelphis domestica revealed by calcium-binding proteins. Brain Struct Funct 221, 4505–4523 (2016). https://doi.org/10.1007/s00429-015-1181-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-015-1181-x