The mammalian olfactory system has the natural capacity to regenerate throughout the animal's life span. Despite constant neurogenesis, olfactory sensory neurons project to precise, stereotypical positions in the brain. Here, we identify a critical period of olfactory sensory axon targeting during postnatal development in mouse. Perturbing axon projection beyond postnatal day 7 permanently disrupts targeting specificity of the sensory neurons. In addition, we find that the establishment of the convergence map requires perinatal sensory neurons. Late-born neurons appear to connect with prospective glomeruli based on homotypic interactions among neurons expressing the same odorant receptor. Our results reveal a developmental switch in axon guidance and a mechanism of circuit integration of adult-born neurons.

No abstract

Summary In the developing brain, heightened plasticity during the critical period enables the proper formation of neural circuits. Here we identify the “navigator” neurons, a group of perinatally born olfactory sensory neurons, as playing an essential role in establishing the olfactory map during the critical period. The navigator axons project circuitously in the olfactory bulb and traverse multiple glomeruli before terminating in perspective glomeruli. These neurons undergo a phase of exuberant axon growth and exhibit a shortened lifespan. Single cell transcriptome analyses reveal distinct molecular signatures for the navigators. Extending their lifespan prolongs the period of exuberant growth and perturbs axon convergence. Conversely, genetic ablation experiment indicates that, despite postnatal neurogenesis, only the navigators are endowed with the ability to establish a convergent map. The presence and the proper removal of the navigator neurons are both required to establish tight axon convergence into the glomeruli.

Animals possess an inborn ability to recognize certain odors to avoid predators, seek food and find mates. Innate odor preference has been thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Moreover, exposure to an aversive odor during the critical period abolishes aversion in adulthood in an odor-specific manner. The loss of innate aversion is associated with broadened projection of OSNs. Thus, a delicate balance of neural activity is required during the critical period in establishing innate odor preference and ectopic projection is a convergent mechanism to alter innate odor valence.

Odors carrying intrinsic values often trigger instinctive aversive or attractive responses.Innate valence is thought to be conveyed through hardwired circuits along the olfactory pathway, insulated from influences of other odors. Here we show that in mice, mixing of innately aversive or attractive odors with a neutral odor abolishes the behavioral responses. Surprisingly, mixing of two odors with the same valence also abolishes the expected responses. Recordings from the olfactory bulb indicate that odors are not masked at the level of peripheral activation and glomeruli independently encode components in the mixture. However, crosstalk among the mitral/tufted cells changes their patterns of activity such that those elicited by the congruent mixtures can no longer be decoded as separate components. The changes in behavioral and mitral/tufted cell responses are associated with reduced activation of brain areas linked to odor preferences. Thus, interactions of odor channels at the earliest processing stage in the olfactory pathway lead to re-coding of odor identity. These results are inconsistent with insulated labeled lines and support a model of a common mechanism of odor recognition for both innate and learned valence associations.