A Population of Navigator Neurons Is Essential for Olfactory Map Formation during the Critical Period

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.

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

“…The presence of Ace2 and Tmprss2 transcripts in mouse WOM and their absence in purified OSNs suggest that the molecular components that enable CoV-2 entry into cells are largely expressed in non-neuronal cell types in the mouse nasal epithelium. To identify the specific cell types that express Ace2 and Tmprss2, we examined two recently published mouse OE scSeq datasets 49,50 . This analysis confirmed our results from bulk RNA-seq, as mature OSNs from either dataset did not express Ace2 (zero cells express Ace2 out of 5337 and 51 OSNs, respectively, Figures 2C, 2D).…”

“…Single-cell RNA-seq data from Wu et al 50 were downloaded from the Gene Expression Omnibus (GEO) at accession GSE120199. These data consisted of dissociated cells from the mouse olfactory epithelium from four developmental time points (P0, P3, P7, P21).…”

“…It therefore remains unclear whether any cell types in the OE express ACE2, TMPRSS2 or other molecules involved in coronavirus entry, which would render them susceptible to direct infection by CoV-2. To address the hypothesis that CoV-2 causes anosmia through primary effects on the OE, we queried publicly available mouse, nonhuman primate and human RNA sequencing (RNASeq) and scSeq datasets that include definitive OE populations to assess CoV-2-related gene expression 37,46,[48][49][50][51][52][53][54][55] . We also mapped scSeq data across different datasets to compare observed gene expression levels from nasal samples to samples obtained from other airway tissues.…”

Developmental regulation of olfactory circuit formation in mice

“…Although OSNs are replaced and form new connections with M/T cells, proper circuits cannot be regenerated once the existing OSNs are completely ablated after the early neonatal period. This time frame of circuit formation has been referred to as the critical period in the mouse olfactory system (Ma et al, 2014; Tsai & Barnea, 2014; Wu et al, 2018). However, the critical period has not been precisely defined at the molecular level, and the key process that makes this time‐window critical has yet to be clarified.…”

Acquisition of Innate Odor Preference Depends on Spontaneous and Experiential Activities During Critical Period

“…The receptor activities drive specific temporal patterns of action potential firing (Nakashima et al, 2019). Spontaneous activity influences the development of the olfactory glomerular map during the critical period (Ma et al, 2014;Tsai and Barnea, 2014;Wu et al, 2018). The olfactory map that formed during this period persists into adulthood.…”