The influence of olfactory experience on the birthrates of olfactory sensory neurons with specific odorant receptor identities.

Olfactory sensory neurons (OSNs) are one of a few neuron types that are generated continuously throughout life in mammals. The persistence of olfactory sensory neurogenesis beyond early development has long been thought to function simply to replace neurons that are lost or damaged through exposure to environmental insults. The possibility that olfactory sensory neurogenesis may also serve an adaptive function has received relatively little consideration, largely due to the assumption that the generation of new OSNs is stochastic with respect to OSN subtype, as defined by the single odorant receptor gene that each neural precursor stochastically chooses for expression out of hundreds of possibilities. Accordingly, the relative birthrates of different OSN subtypes are predicted to be constant and impervious to olfactory experience. This assumption has been called into question, however, by evidence that the birthrates of specific OSN subtypes can be selectively altered by manipulating olfactory experience through olfactory deprivation, enrichment, and conditioning paradigms. Moreover, studies of recovery of the OSN population following injury provide further evidence that olfactory sensory neurogenesis may not be strictly stochastic with respect to subtype. Here we review this evidence and consider mechanistic and functional implications of the prospect that specific olfactory experiences can regulate olfactory sensory neurogenesis rates in a subtype-selective manner.

In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate.

In mammals, olfactory sensory neurons (OSNs) are born throughout life, presumably solely to replace neurons lost via turnover or injury. This assumption follows from the hypothesis that olfactory neurogenesis is strictly stochastic with respect to neuron subtype, as defined by the single odorant receptor allele that each neural precursor stochastically chooses out of hundreds of possibilities. This hypothesis is challenged by recent findings that the birthrates of a fraction of subtypes are selectively diminished by olfactory deprivation. These findings raise questions about how, and why, olfactory stimuli are required to promote the neurogenesis of some OSN subtypes, including whether the stimuli are generic (e.g., broadly activating odors or mechanical stimuli) or specific (e.g., discrete odorants). Based on RNA-seq and scRNA-seq analyses, we hypothesized that the neurogenic stimuli are specific odorants that selectively activate the same OSN subtypes whose birthrates are accelerated. In support of this, we have found, using subtype-specific OSN birthdating, that exposure to male and musk odors can accelerate the birthrates of responsive OSNs. Collectively, our findings reveal that certain odor experiences can selectively "amplify" specific OSN subtypes, and that persistent OSN neurogenesis may serve, in part, an adaptive function.