Abstract

Survival of many altricial animals critically depends on the sense of smell. Curiously, the olfactory system is rather immature at birth and undergoes a maturation process, which is poorly understood. Using patch-clamp technique on mouse olfactory sensory neurons (OSNs) with a defined odorant receptor, we demonstrate that OSNs exhibit functional maturation during the first month of postnatal life by developing faster response kinetics, higher sensitivity, and most intriguingly, higher selectivity. OSNs expressing mouse odorant receptor 23 (MOR23) are relatively broadly tuned in neonates and become selective detectors for the cognate odorant within 2 weeks. Remarkably, these changes are prevented by genetic ablation of olfactory marker protein (OMP), which is exclusively expressed in mature OSNs. Biochemical and pharmacological evidence suggests that alteration in odorant-induced phosphorylation of signaling proteins underlie some of the OMP^−/− phenotypes. Furthermore, in a novel behavioral assay in which the mouse pups are given a choice between the biological mother and another unfamiliar lactating female, wild-type pups prefer the biological mother, while OMP knock-out pups fail to show preference. These results reveal that OSNs undergo an OMP-dependent functional maturation process that coincides with early development of the smell function, which is essential for pups to form preference for their mother.