The glomerular map in the olfactory bulb (OB) is the basis for odor recognition. Once established during development, the glomerular map is stably maintained throughout the life of an animal despite the continuous turnover of olfactory sensory neurons (OSNs). However, traumatic damage to OSN axons in the adult often leads to dysosmia, a qualitative and quantitative change in olfaction in human. A mouse model of dysosmia has previously indicated that there is an altered glomerular map in the OB after the OSN axon injury; however, the underlying mechanisms that cause the map distortion remain unknown. In this study, we examined how the glomerular map is disturbed and how the odor information processing in the OB is affected in the dysosmia model mice. We found that the anterior-posterior coarse targeting of OSN axons is disrupted after OSN axon injury, while the local axon sorting mechanisms remained. We also found that the connectivity of mitral/tufted cell dendrites is reduced after injury, leading to attenuated odor responses in mitral/tufted cells. These results suggest that existing OSN axons are an essential scaffold for maintaining the integrity of the olfactory circuit, both OSN axons and mitral/tufted cell dendrites, in the adult.
Significance Statement: Olfactory sensory neurons (OSNs) have a unique ability to regenerate throughout the life of animals. Therefore, OSNs are newly generated and project to the olfactory bulb (OB) even after injury. However, it has been known that severe head trauma, which accompanies the transection of OSN axons, often leads to dysosmia (qualitative and quantitative changes in olfaction). Currently there is no effective therapy for dysosmia patients. To gain mechanistic insights, we investigated the anatomical and functional changes of the olfactory system after OSN axon injury, and found defects in coarse OSN axon targeting and dendrite connectivity of mitral cells. Based on these findings, possible future strategies for dysosmia will be discussed.
The authors declare no competing financial interests.
This work was supported by the intramural grant of RIKEN Center for Developmental Biology, JST PRESTO program, and JSPS KAKENHI (Grant numbers 23680038, 15H05572, 15K14336, 16K14568, and 16H06456) to T.I.