The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain.
Bibliographical noteFunding Information:
We thank Dr. Peter Mombaerts of the Max Planck Institute of Biophysics Frankfurt, Germany for the generous gift of mice strains. We also thank Diana Millán and Marcela Palomero for their excellent technical assistance. We are grateful to Fernanda Monjaraz for insightful comments to the manuscript. EBH received a Ph.D. fellowship from CONACYT-México. This work is part of the fulfillment of requirements for EBH's Ph.D. degree in Biomedical Science from the Universidad Nacional Autónoma de México. We are indebted to Claudia Rivera and her staff of the animal facility for their assistance and continuous advice. Ana Maria Escalante and Francisco Pérez-Eugenio provided us with excellent computer technical assistance.
All Science Journal Classification (ASJC) codes
- General Biochemistry,Genetics and Molecular Biology
- General Agricultural and Biological Sciences