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Low survival rate of young adult-born olfactory sensory neurons in the undamaged mouse olfactory epithelium

  • Sajishnu P. Savya
  • Tenzin Kunkhyen
  • Claire E. J. Cheetham
Article
  • 55 Downloads

Abstract

Olfactory sensory neurons (OSNs) are generated throughout life from progenitor cells in the olfactory epithelium. OSN axons project in an odorant receptor-specific manner to the olfactory bulb (OB), forming an ordered array of glomeruli where they provide sensory input to OB neurons. The tetracycline transactivator (tTA) system permits developmental stage-specific expression of reporter genes in OSNs and has been widely used for structural and functional studies of the development and plasticity of the mouse olfactory system. However, the cellular ages at which OSNs stop expressing reporters driven by the immature OSN-specific Gγ8-tTA driver line and begin to express reporters driven by the mature OSN-specific OMP-tTA driver line have not been directly determined. We pulse-labeled terminally dividing cells in the olfactory epithelium of 28-day-old (P28) mice with EdU and analyzed EdU labeling in OSNs expressing fluorescent reporter proteins under control of either the Gγ8-tTA or OMP-tTA driver line 5–14 days later. Expression of OMP-tTA-driven reporters began in 6-day-old OSNs, while the vast majority of newborn OSNs did not express Gγ8-tTA-driven fluorescent proteins beyond 8 days of cellular age. Surprisingly, we also found a low survival rate for P28-born OSNs, very few of which survived for more than 14 days. We propose that OSN survival requires the formation of stable synaptic connections and hence may be dependent on organismal age.

Keywords

Adult neurogenesis Olfactory sensory neuron Olfactory epithelium Neuronal survival 

Notes

Acknowledgements

This work was supported by grants to CEJC from the National Institute on Deafness and other Communication Disorders (R03DC014788) and the Samuel and Emma Winters Foundation. We thank Gerry Hammond (University of Pittsburgh) for use of the Nikon A1R confocal microscope.

References

  1. Batista-Brito R, Close J, Machold R, Fishell G (2008) The distinct temporal origins of olfactory bulb interneuron subtypes. J Neurosci 28:3966–3975.  https://doi.org/10.1523/JNEUROSCI.5625-07.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Brann JH, Ellis DP, Ku BS, Spinazzi EF, Firestein S (2015) Injury in aged animals robustly activates quiescent olfactory neural stem cells. Front Neurosci 9:367.  https://doi.org/10.3389/fnins.2015.00367 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Caggiano M, Kauer J, Hunter D (1994) Globose basal cells are neuronal progenitors in the olfactory epithelium: a lineage analysis using a replication-incompetent retrovirus. Neuron 13:339–352.  https://doi.org/10.1016/0896-6273(94)90351-4 CrossRefPubMedGoogle Scholar
  4. Cheetham C, Park U, Belluscio L (2016) Rapid and continuous activity-dependent plasticity of olfactory sensory input. Nat Commun 7:10729.  https://doi.org/10.1038/ncomms10729 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Coleman JH, Lin B, Schwob JE (2017) Dissecting LSD1-dependent neuronal maturation in the olfactory epithelium. J Comp Neurol 525:3391–3413.  https://doi.org/10.1002/cne.24259 CrossRefPubMedGoogle Scholar
  6. Farbman A (1992) Cell biology of olfaction. Cambridge University Press, CambridgeGoogle Scholar
  7. Farbman A, Margolis F (1980) Olfactory marker protein during ontogeny: immunohistochemical localization. Dev Biol 74:205–215CrossRefPubMedGoogle Scholar
  8. Godfrey P, Malnic B, Buck L (2004) The mouse olfactory receptor gene family. Proc Natl Acad Sci U S A 101:2156–2161.  https://doi.org/10.1073/pnas.0308051100 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Graziadei MG (1983) Experimental studies on the olfactory marker protein. III. The olfactory marker protein in the olfactory neuroepithelium lacking connections with the forebrain. Brain Res 262:303–308CrossRefGoogle Scholar
  10. Graziadei P, Monti Graziadei G (1978) Continuous nerve cell renewal in the olfactory system. In: Jacobson M (ed) Development of sensory systems. Springer-Verlag, Berlin, Heidelberg, pp 55–83CrossRefGoogle Scholar
  11. Hahn C, Han L, Rawson N, Mirza N, Borgmann-Winter K, Lenox R, Arnold S (2005) In vivo and in vitro neurogenesis in human olfactory epithelium. J Comp Neurol 483:154–163.  https://doi.org/10.1002/cne.20424 CrossRefPubMedGoogle Scholar
  12. Hinds J, Hinds P, McNelly N (1984) An autoradiographic study of the mouse olfactory epithelium: evidence for long-lived receptors. Anat Rec 210:375–383.  https://doi.org/10.1002/ar.1092100213 CrossRefPubMedGoogle Scholar
  13. Holl A (2018) Survival of mature mouse olfactory sensory neurons labeled genetically perinatally. Mol Cell Neurosci 88:258–269.  https://doi.org/10.1016/j.mcn.2018.02.005 CrossRefPubMedGoogle Scholar
  14. Kikuta S, Sakamoto T, Nagayama S, Kanaya K, Kinoshita M, Kondo K, Tsunoda K, Mori K, Yamasoba T (2015) Sensory deprivation disrupts homeostatic regeneration of newly generated olfactory sensory neurons after injury in adult mice. J Neurosci 35:2657–2673.  https://doi.org/10.1523/JNEUROSCI.2484-14.2015 CrossRefPubMedGoogle Scholar
  15. Kondo K, Suzukawa K, Sakamoto T, Watanabe K, Kanaya K, Ushio M, Yamaguchi T, Nibu KI, Kaga K, Yamasoba T (2010) Age-related changes in cell dynamics of the postnatal mouse olfactory neuroepithelium: cell proliferation, neuronal differentiation, and cell death. J Comp Neurol 518:1962–1975.  https://doi.org/10.1002/cne.22316 CrossRefPubMedGoogle Scholar
  16. Leung C, Coulombe P, Reed R (2007) Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci 10:720–726.  https://doi.org/10.1038/nn1882 CrossRefPubMedGoogle Scholar
  17. Li X, Zhao X, Fang Y, Jiang X, Duong T, Fan C, Huang CC, Kain SR (1998) Generation of destabilized green fluorescent protein as a transcription reporter. J Biol Chem 273:34970–34975CrossRefPubMedGoogle Scholar
  18. Mackay-Sim A, Kittel P (1991) On the life span of olfactory receptor neurons. Eur J Neurosci 3:209–215CrossRefGoogle Scholar
  19. Malnic B, Godfrey P, Buck L (2004) The human olfactory receptor gene family. Proc Natl Acad Sci U S A 101:2584–2589CrossRefPubMedPubMedCentralGoogle Scholar
  20. McIntyre JC, Titlow WB, McClintock TS (2010) Axon growth and guidance genes identify nascent, immature, and mature olfactory sensory neurons. J Neurosci Res 88:3243–3256.  https://doi.org/10.1002/jnr.22497 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Miragall F, Graziadei G (1982) Experimental studies on the olfactory marker protein. II. Appearance of the olfactory marker protein during differentiation of the olfactory sensory neurons of mouse: an immunohistochemical and autoradiographic study. Brain Res 239:245–250.  https://doi.org/10.1016/0006-8993(82)90846-0 CrossRefPubMedGoogle Scholar
  22. Mombaerts P, Wang F, Dulac C, Chao SK, Nemes A, Mendelsohn M, Edmondson J, Axel R (1996) Visualizing an olfactory sensory map. Cell 87:675–686CrossRefPubMedGoogle Scholar
  23. Nguyen M, Zhou Z, Marks C et al (2007) Prominent roles for odorant receptor coding sequences in allelic exclusion. Cell 131:1009–1017.  https://doi.org/10.1016/j.cell.2007.10.050 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Potter S, Zheng C, Koos D et al (2001) Structure and emergence of specific olfactory glomeruli in the mouse. J Neurosci 21:9713–9723CrossRefPubMedPubMedCentralGoogle Scholar
  25. Ressler K, Sullivan S, Buck L (1993) A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell 73:597–609CrossRefPubMedGoogle Scholar
  26. Ressler K, Sullivan S, Buck L (1994) Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79:1245–1255.  https://doi.org/10.1016/0092-8674(94)90015-9 CrossRefGoogle Scholar
  27. Rodriguez-Gil DJ, Bartel DL, Jaspers AW, Mobley AS, Imamura F, Greer CA (2015) Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons. Proc Natl Acad Sci U S A 112:5821–5826.  https://doi.org/10.1073/pnas.1417955112 CrossRefPubMedPubMedCentralGoogle Scholar
  28. Roskams A, Cai X, Ronnett G (1998) Expression of neuron-specific beta-III tubulin during olfactory neurogenesis in the embryonic and adult rat. Neuroscience 83:191–200CrossRefPubMedGoogle Scholar
  29. Ryba N, Tirindelli R (1995) A novel GTP-binding protein gamma-subunit, G gamma 8, is expressed during neurogenesis in the olfactory and vomeronasal neuroepithelia. J Biol Chem 270:6757–6767CrossRefPubMedGoogle Scholar
  30. Saraiva L, Ibarra-Soria X, Khan M, et al (2016) Hierarchical deconstruction of mouse olfactory sensory neurons: from whole mucosa to single-cell RNA-seq. Scientific Reports 5:srep18178. doi:  https://doi.org/10.1038/srep18178
  31. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJ, Hartenstein V, Eliceiri K, Tomancak P, Cardona A (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9:676–682.  https://doi.org/10.1038/nmeth.2019 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Schwob J (1992) The biochemistry of olfactory neurons: stages of differentiation and neuronal subsets. In: Serby MJ, Chobor KL (eds) Science of olfaction. Springer, New York, pp 80–125CrossRefGoogle Scholar
  33. Schwob J, Szumowski K, Stasky A (1992) Olfactory sensory neurons are trophically dependent on the olfactory bulb for their prolonged survival. J Neurosci 12:3896–3919CrossRefPubMedGoogle Scholar
  34. Schwob J, Jang W, Holbrook E et al (2017) Stem and progenitor cells of the mammalian olfactory epithelium: taking poietic license. J Comp Neurol 525:1034–1054.  https://doi.org/10.1002/cne.24105 CrossRefPubMedGoogle Scholar
  35. Strotmann J, Wanner I, Krieger J, Raming K, Breer H (1992) Expression of odorant receptors in spatially restricted subsets of chemosensory neurones. Neuroreport 3:1053–1056CrossRefPubMedGoogle Scholar
  36. Tirindelli R, Ryba N (1996) The G-protein gamma-subunit G gamma 8 is expressed in the developing axons of olfactory and vomeronasal neurons. Eur J Neurosci 8:2388–2398CrossRefPubMedGoogle Scholar
  37. Vassar R, Ngai J, Axel R (1993) Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell 74:309–318CrossRefPubMedGoogle Scholar
  38. Vassar R, Chao SK, Sitcheran R, Nuñez JM, Vosshall LB, Axel R (1994) Topographic organization of sensory projections to the olfactory bulb. Cell 79:981–991CrossRefPubMedGoogle Scholar
  39. Vedin V, Molander M, Bohm S, Berghard A (2009) Regional differences in olfactory epithelial homeostasis in the adult mouse. J Comp Neurol 513:375–384.  https://doi.org/10.1002/cne.21973 CrossRefPubMedGoogle Scholar
  40. Verhaagen J, Oestreicher A, Gispen W, Margolis F (1989) The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats. J Neurosci 9:683–691CrossRefPubMedGoogle Scholar
  41. Verhaagen J, Oestreicher A, Grillo M et al (1990) Neuroplasticity in the olfactory system: differential effects of central and peripheral lesions of the primary olfactory pathway on the expression of B-50/GAP43 and the olfactory marker protein. J Neurosci Res 26:31–44.  https://doi.org/10.1002/jnr.490260105 CrossRefPubMedGoogle Scholar
  42. Yu C, Power J, Barnea G et al (2004) Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42:553–566CrossRefPubMedGoogle Scholar
  43. Zou D-JJ, Feinstein P, Rivers AL et al (2004) Postnatal refinement of peripheral olfactory projections. Science 304:1976–1979.  https://doi.org/10.1126/science.1093468 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurobiologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Biological SciencesCarnegie Mellon UniversityPittsburghUSA

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