Sensory Deprivation Disrupts Homeostatic Regeneration of Newly Generated Olfactory Sensory Neurons after Injury in Adult Mice

Abstract

Although it is well known that injury induces the generation of a substantial number of new olfactory sensory neurons (OSNs) in the adult olfactory epithelium (OE), it is not well understood whether olfactory sensory input influences the survival and maturation of these injury-induced OSNs in adults. Here, we investigated whether olfactory sensory deprivation affected the dynamic incorporation of newly generated OSNs 3, 7, 14, and 28 d after injury in adult mice. Mice were unilaterally deprived of olfactory sensory input by inserting a silicone tube into their nostrils. Methimazole, an olfactotoxic drug, was also injected intraperitoneally to bilaterally ablate OSNs. The OE was restored to its preinjury condition with new OSNs by day 28. No significant differences in the numbers of olfactory marker proteinpositive mature OSNs or apoptotic OSNs were observed between the deprived and nondeprived sides 0 -7 d after injury. However, between days 7 and 28, the sensory-deprived side showed markedly fewer OSNs and mature OSNs, but more apoptotic OSNs, than the nondeprived side. Intrinsic functional imaging of the dorsal surface of the olfactory bulb at day 28 revealed that responses to odor stimulation were weaker in the deprived side compared with those in the nondeprived side. Furthermore, prevention of cell death in new neurons 7-14 d after injury promoted the recovery of the OE. These results indicate that, in the adult OE, sensory deprivation disrupts compensatory OSN regeneration after injury and that newly generated OSNs have a critical time window for sensory-input-dependent survival 7-14 d after injury.

Rapid and continuous activity-dependent plasticity of olfactory sensory input

“…Although it remains to be determined how rapidly OSN presynaptic terminal turnover is affected by naris occlusion, it is clear that the marked reduction in OSN presynaptic terminal turnover elicited by 3 weeks of naris occlusion was not a consequence of changes at the level of the olfactory epithelium, as we found no effect of naris occlusion on numbers of immature or mature OSNs, or proliferating or apoptotic cells. This is in agreement with a recent study, which found no change in epithelium thickness, total number of OSNs or number of OMP+ OSNs at time points 3–28 days post naris occlusion in adult mice 46 . Hence, a transient effect of naris occlusion on OSN survival is also unlikely.…”

Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

“…The equilibrium between OSN survival and apoptosis is possibly regulated by odorant-stimulated neural activity and sensory experience (Zhao et al, 2013; Cadiou et al, 2014; Kikuta et al, 2015). Sensory input plays a critical role in the survival of OSNs during postnatal MOE development (Farbman et al, 1988; Stahl et al, 1990; Brunjes, 1994; Coppola et al, 2006).…”

Chitosan-hyaluronan: promotion of mucociliary differentiation of respiratory epithelial cells and development of olfactory receptor neurons

“…Olfactory dysfunction is a frequent complaint in CRS patients and significantly affects their quality of life [26]. The etiology results from a long-term inflammatory process that causes respiratory metaplasia, airway obstruction and incomplete ORN regeneration [26,27]. Although CS interferes with the formation of tight junction and impedes mucociliary differentiation of RECs, it is a promising agent to facilitate the ORN differentiation of ONCs.…”