Elsevier

Neuroscience

Volume 119, Issue 2, 27 June 2003, Pages 507-516
Neuroscience

Neuropharmacology
Deprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice

https://doi.org/10.1016/S0306-4522(03)00172-6Get rights and content

Abstract

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.

Section snippets

Animals

Adult male C57Bl/6J mice (IFFA CREDO, L’Arbresles, France) aged 8–12 weeks at the beginning of the experiment were used. All animals were housed under a 12 h light/dark cycle with food and water available ad libitum. All efforts were made to minimize the number of animals used and their suffering during the experimental procedure in accordance with the European Community Council Directive of November 24, 1986 (86/609/EEC), and the French Ethical Committee. Mice were subjected to unilateral

Axotomy-induced reduction in OE thickness and recovery

The thickness of the OE was reduced by 23±4% (mean±S.E.M., P<0.0001) 6 days post-axotomy (Fig. 2) compared with the non-operated side, indicative of the massive death of mature disconnected ORNs. From 12–30 days post-axotomy, the thickness of the OE on the lesioned side slowly recovered and returned to normal values at 60 days post-axotomy. The thickness of the OE in sham-operated controls was not statistically different from the non-operated side of axotomized animals.

Olfactory axotomy increases cell death in the RMS-OB, RMS and SVZ

Apoptosis was measured

Discussion

In the present report, cell death and proliferation increased in the SVZ, RMS and RMS-OB during the first 2 weeks following olfactory deafferentation by axotomy and returned to control values 1 month after deafferentation. These changes closely followed the temporal pattern of ORNs death and regeneration. In addition, it has been shown that responses to odorants can be recorded from MOB cells starting 1 month post-axotomy (Costanzo, 1985). These data strongly suggest that the changes in cell

Conclusion

Three main findings arise from the present study. (1) Following axotomy cell death in the RMS targets migrating neuroblasts suggesting that they depend upon olfactory inputs for their survival. (2) Proliferation is enhanced following axotomy with a spatio-temporal pattern which only partly mirrors increased cell death. This observation suggests that proliferation does not only balance cell death but may be governed by a larger set of mechanisms. (3) Evidence is provided for the existence of a

Acknowledgements

This work was supported by Région Rhône-Alpes (Program Emergence) and Fondation Roudnitska (Fellowship to N.M.). We thank Dr. G. Grenningloh for the gift of the anti-stathmin antibody. Many thanks to Drs. Giannetti, Marcel and Pellier for helpful discussions. We are grateful to Dr. P. M. Lledo for comments on the manuscript.

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