Abstract

The vomeronasal organ (VNO) specializes in detection of chemosignals, mainly pheromones, which control social communication and reproduction in many mammals. These pheromones must solubilize with nasal fluids before entering the VNO, and it was suggested that they are delivered to and cleared from the VNO by active pumping. Yet, the details of this pheromone delivery process are unclear. In this study, we first constructed a high-resolution 3D morphological image of the whole adult mouse snout, by using ultra-high-resolution micro-CT. We identified a net of micro tunnels starting from the nostrils and extending around and through the VNO. These micro tunnels connect the nasal cavity with the VNO and the oral cavity via the nasopalatine ducts (NPD). Other micro tunnels connect the nasal cavity to the main olfactory epithelium. We next demonstrated that physical obstruction of the NPD severely impairs the clearance of dissolved compounds from the VNO lumen. Moreover, we found that mice with blocked NPD display alterations in chemosignaling-evoked neuronal activation in brain regions associated with the vomeronasal system. Finally, NPD-blocked male mice exhibit reduced preference for female chemosignals, and impaired social interaction behavior. Taken together, our findings indicate that the NPD in mice are connected to both the nasal and oral cavity, serving an essential role in regulating the flow of soluble chemosignals through the VNO, and are required for proper pheromone-mediated social communication.

Highlights

  • The vomeronasal organ (VNO) plays a key role in detecting sex-specific and species-specific chemical signals (Keverne, 1999; Stowers et al, 2002; Dulac and Torello, 2003; Halpern and Martıìnez-Marcos, 2003; Dulac and Kimchi, 2007; Isogai et al, 2011; Beny and Kimchi, 2014; Bear et al, 2016; Marom et al, 2019)

  • The scans revealed a net of micro tunnels (∼100 μm in diameter, marked in arrows) which start at the nostrils and branch into two main routs: one leads to the rear end of the nasal cavity, while the other leads to the VNO (Figures 1D,E)

  • The posterior opening appears to be directly connected to the network of micro tunnels leading to the nasopalatine ducts (NPD), and could potentially enable a passageway for chemosignals between the oral cavity, VNO and nasal cavity

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Summary

Introduction

The vomeronasal organ (VNO) plays a key role in detecting sex-specific and species-specific chemical signals (Keverne, 1999; Stowers et al, 2002; Dulac and Torello, 2003; Halpern and Martıìnez-Marcos, 2003; Dulac and Kimchi, 2007; Isogai et al, 2011; Beny and Kimchi, 2014; Bear et al, 2016; Marom et al, 2019). It is assumed that chemosignals are delivered to the VNO through the nostrils, by active sniffing (Vaccarezza et al, 1981; Dulac and Torello, 2003), while the VNO serves as an active pump to guide molecules into its epithelium (Eccles, 1982; Meredith, 1994). The VNO itself is secluded from airflow and is engulfed by a bony capsule; chemosignals delivered into the nostrils (by sniffing) must solubilize with nasal fluids, before entering the VNO through active pumping (Meredith and O’Connell, 1979). A characterization of the full process by which chemosignals flow through, and especially cleared from the VNO lumen to allow delivery of new chemosignals, is still missing

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