Low survival rate of young adult-born olfactory sensory neurons in the undamaged mouse olfactory epithelium
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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.
KeywordsAdult neurogenesis Olfactory sensory neuron Olfactory epithelium Neuronal survival
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.
- Farbman A (1992) Cell biology of olfaction. Cambridge University Press, CambridgeGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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