Deprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice.
The main olfactory bulb (MOB) is the first relay on the olfactory sensory pathway and the target of the neural progenitor cells generated in the subventricular zone (SVZ) lining the lateral ventricles and which migrate along the rostral extension of the SVZ, also called the rostral migratory stream (RMS). Within the MOB, the neuroblasts differentiate into granular and periglomerular interneurons. A reduction in the number of granule cells during sensory deprivation suggests that neurogenesis may be influenced by afferent activity. Here, we show that unilateral sensory deafferentation of the MOB by axotomy of the olfactory receptor neurons increases apoptotic cell death in the SVZ and along the rostro-caudal extent of the RMS. The vast majority of dying cells in the RMS are migrating neuroblasts as indicated by double Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling/PSA-NCAM labeling. Counting bromodeoxyuridine-labeled cells in animals killed immediately or 4 days after tracer administration showed a bilateral increase in proliferation in the SVZ and RMS which was balanced by cell death on the operated side. These data suggest that olfactory inputs are required for the survival of newborn neural progenitors. The greatest enhancement in proliferation occurred in the extension of the RMS located in the MOB, revealing a population of local precursors mitotically stimulated following axotomy. Together, these findings indicate that olfactory inputs may strongly modulate the balance between neurogenesis and apoptosis in the SVZ and RMS and provide a model for further investigation of the underlying molecular mechanisms of this activity-dependent neuronal plasticity.
Mandairon
N
N
Laboratoire de Neurosciences et Systèmes Sensoriels, CNRS UMR 5020, Université Claude Bernard-Lyon 1, 50 Avenue Tony Garnier, 69366 Lyon Cedex 07, France.
Jourdan
F
F
Didier
A
A
D000818:Animals; D019771:Axotomy / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement; D002470:Cell Survival; D002552:Cerebral Ventricles / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology* / Q000378:metabolism; D009831:Olfactory Mucosa / Q000473:pathology; D009833:Olfactory Pathways / Q000293:injuries*; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D019006:Neural Cell Adhesion Molecules; D001973:Bromodeoxyuridine