Molecular diversity and connectivity of accessory olfactory system neurons

Abstract

Olfaction is the primary sensory modality by which most vertebrate species interpret environmental cues for appropriate behavioral outputs. The olfactory system is subdivided into main (MOS) and accessory (AOS) components which process volatile and non-volatile cues. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the AOS which is largely comprised of the peripheral vomeronasal organ (VNO), the accessory olfactory bulb (AOB) and the medial subnucleus of the amygdala (MeA), we studied the molecular diversity and neuronal subtype connectivity of this interconnected circuit. We show that populations of neurons of the AOS can be molecularly subdivided based on their current or prior expression of the transcription factorsFoxp2orDbx1. We show that the majority of AOB neurons that project directly to the MeA are of theFoxp2-lineage. Using single cell patch clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the relative contributions of excitatory and inhibitory inputs to MeAFoxp2-lineage neurons differ between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons and lineage- and sex-differences in patterns of connectivity.

Diversity within olfactory sensory derivatives revealed by the contribution of Dbx1 lineages

“…Nevertheless, the previous description we made of early (E8.5) Dbx1-expressing progenitors contributing to a subset of cranial neural crests cells (Causeret et al, 2011) could support a certain degree of overlap between the two lineages. Furthermore, a recent preprint investigating the cellular diversity and connectivity patterns in the accessory olfactory system reported that Dbx1-driven diversity is not only observed in the VNO but also in the accessory olfactory bulb and medial amygdala (Prakash et al, 2022). This work points to the idea of a molecular code involved in the assembly of olfactory circuits that would be conserved from the sensory epithelia to the central processing structures.…”

“…Furthermore, a recent preprint investigating the cellular diversity and connectivity patterns in the accessory olfactory system reported that Dbx1-driven diversity is not only observed in the VNO but also in the accessory olfactory bulb and medial amygdala (Prakash et al, 2022). This work points to the idea of a molecular code involved in the assembly of olfactory circuits that would be conserved from the sensory epithelia to the central processing structures.…”

Diversity within olfactory sensory derivatives revealed by the contribution of Dbx1 lineages

“…In this perspective, it is worth mentioning that we previously described a partial overlap between Wnt1 and Dbx1 lineages (Causeret et al., 2011) as well as a regulatory loop between Pax7 and Dbx1 (Gard et al., 2017). Furthermore, a recent preprint investigating the cellular diversity and connectivity patterns in the accessory olfactory system reported that Dbx1‐driven diversity is not only observed in the VNO but also in the accessory olfactory bulb and medial amygdala (Prakash et al., 2022). This work points to the idea of a molecular code involved in the assembly of olfactory circuits that would be conserved from the sensory epithelia to the central processing structures.…”