title: Functional rehabilitation of cadmium-induced neurotoxicity despite persistent peripheral pathophysiology in the olfactory system.
abstract: Intranasal exposure to the heavy metal cadmium has been linked to olfactory dysfunction and neurotoxicity. Here, we combine optical imaging of in vivo neurophysiology, genetically defined anatomical tract tracing, mass spectrometry, and behavioral psychophysical methods to evaluate the persistent harmful effects of acute intranasal exposure to cadmium in a mouse model and to investigate the functional consequences of sensory rehabilitation training. We find that an acute intranasal instillation of cadmium chloride leads to an accumulation of cadmium in the brain's olfactory bulb that persists for at least 4 weeks. This is accompanied by persistent severe pathophysiology of the olfactory nerve, a gradual reduction in axonal projections from the olfactory epithelium, and complete impairment on an olfactory detection task. Remarkably, 2 weeks of odorant-guided operant conditioning training proved sufficient to restore olfactory detection performance to control levels in cadmium-exposed mice. Optical imaging from rehabilitated mice showed that this training did not cause any detectable restoration of olfactory nerve function, suggesting that the recovery of function was mediated by central neuroplasticity in which the brain learned to interpret the degraded sensory input. These data demonstrate that sensory learning can mask even severe damage from neurotoxicants and suggest that explicit sensory training may be useful in rehabilitation of olfactory dysfunction.
authors.affiliation: Behavioral Neuroscience Section, Department of Psychology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Czarnecki
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Moberly
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Turkel
authors.forename: Tom
authors.initials: T
authors.lastname: Rubinstein
authors.forename: Joseph
authors.initials: J
authors.lastname: Pottackal
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Rosenthal
authors.forename: Elizabeth F K
authors.initials: EF
authors.lastname: McCandlish
authors.forename: Brian
authors.initials: B
authors.lastname: Buckley
authors.forename: John P
authors.initials: JP
authors.lastname: McGann
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D009420:Nervous System / Q000187:drug effects*; D009833:Olfactory Pathways / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D002104:Cadmium