Abstract
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.
Highlights
The olfactory system offers a unique opportunity to study the mechanisms of neuronal regeneration
M72 circuits are restored after methimazole treatment The temporal course of axonal regeneration of neurons expressing the M72 receptor was followed during 45 days after methimazole administration
These M72-expressing olfactory sensory neurons (OSNs) are located in the dorsal portion of the nasal turbinates
Summary
The olfactory system offers a unique opportunity to study the mechanisms of neuronal regeneration. Lying on the olfactory epithelia (OE), olfactory sensory neurons (OSNs) are responsible for the initial process of odorant detection. This neuronal population is replaced continuously during adult life [1,2,3]. Several studies have shown the remarkable capability of regeneration of OSNs in the OE and reinnervation of their postsynaptic targets in the olfactory bulb (OB) after diverse insults [4,5,6,7]. All the OSNs expressing a specific OR innervate the same area of the OB, where their axons coalesce and form functional circuits called glomeruli
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