title: Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb.
abstract: The olfactory system has a unique capacity for recovery from peripheral damage. After injury to the olfactory epithelium (OE), olfactory sensory neurons (OSNs) regenerate and re-converge on target glomeruli of the olfactory bulb (OB). Thus far, this process has been described anatomically for only a few defined populations of OSNs. Here we characterize this regeneration at a functional level by assessing how odor representations carried by OSN inputs to the OB recover after massive loss and regeneration of the sensory neuron population. We used chronic imaging of mice expressing synaptopHluorin in OSNs to monitor odor representations in the dorsal OB before lesion by the olfactotoxin methyl bromide and after a 12 week recovery period. Methyl bromide eliminated functional inputs to the OB, and these inputs recovered to near-normal levels of response magnitude within 12 weeks. We also found that the functional topography of odor representations recovered after lesion, with odorants evoking OSN input to glomerular foci within the same functional domains as before lesion. At a finer spatial scale, however, we found evidence for mistargeting of regenerated OSN axons onto OB targets, with odorants evoking synaptopHluorin signals in small foci that did not conform to a typical glomerular structure but whose distribution was nonetheless odorant-specific. These results indicate that OSNs have a robust ability to reestablish functional inputs to the OB and that the mechanisms underlying the topography of bulbar reinnervation during development persist in the adult and allow primary sensory representations to be largely restored after massive sensory neuron loss.
authors.affiliation: Department of Biology, Boston University Boston, MA, USA.
authors.forename: Man C
authors.initials: MC
authors.lastname: Cheung
authors.affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine Boston, MA, USA.
authors.forename: Woochan
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine Boston, MA, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
authors.affiliation: Department of Biology, Boston University Boston, MA, USA ; Brain Institute and Department of Neurobiology and Anatomy, University of Utah Salt Lake City, UT, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Wachowiak
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000254:growth & development*; D009831:Olfactory Mucosa / Q000378:metabolism*; D018035:Receptors, Odorant / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism*
chemical_list: D018035:Receptors, Odorant
keywords: axon targeting; olfactory bulb; regeneration; sensory neurons; synaptopHluorin