Hemoglobin in the blood acts as a chemosensory signal via the mouse vomeronasal system

Takuya Osakada,Hiroko Kimoto,Ken Murata,Kazunari Miyamichi,Takumi Itakura,Sachiko Haga-Yamanaka,Takayuki Abe,Kosuke Saito,Hiromi Mori,Yoshihiro Yoshihara,Ryo Eguchi,Kazushige Touhara,Kentaro K Ishii

doi:10.1038/s41467-022-28118-w

Takuya Osakada, Hiroko Kimoto + Show 11 more

Open Access

https://doi.org/10.1038/s41467-022-28118-w

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Abstract

The vomeronasal system plays an essential role in sensing various environmental chemical cues. Here we show that mice exposed to blood and, consequently, hemoglobin results in the activation of vomeronasal sensory neurons expressing a specific vomeronasal G protein-coupled receptor, Vmn2r88, which is mediated by the interaction site, Gly17, on hemoglobin. The hemoglobin signal reaches the medial amygdala (MeA) in both male and female mice. However, it activates the dorsal part of ventromedial hypothalamus (VMHd) only in lactating female mice. As a result, in lactating mothers, hemoglobin enhances digging and rearing behavior. Manipulation of steroidogenic factor 1 (SF1)-expressing neurons in the VMHd is sufficient to induce the hemoglobin-mediated behaviors. Our results suggest that the oxygen-carrier hemoglobin plays a role as a chemosensory signal, eliciting behavioral responses in mice in a state-dependent fashion.

Highlights

The vomeronasal system plays an essential role in sensing various environmental chemical cues
Nonvolatile cues are detected by vomeronasal receptors in the vomeronasal organ (VNO) located beneath the nasal cavity, and usually convey sociosexual information associated with stereotypical behavior or emotional changes[6,7]
When we discovered the exocrine glandsecreting peptide 1 (ESP1) molecule in 2005, we reported that the submaxillary gland contains a molecule, which activates vomeronasal sensory neurons (VSNs) in the mouse VNO9

Summary

Introduction

The vomeronasal system plays an essential role in sensing various environmental chemical cues. Our results suggest that the oxygencarrier hemoglobin plays a role as a chemosensory signal, eliciting behavioral responses in mice in a state-dependent fashion. Nonvolatile cues are detected by vomeronasal receptors in the vomeronasal organ (VNO) located beneath the nasal cavity, and usually convey sociosexual information associated with stereotypical behavior or emotional changes[6,7]. Secretions, such as urine, tear fluid, and saliva contain both volatile and nonvolatile olfactory cues. The vast majority of V2Rs, remain orphan, limiting our understanding of sensory mechanisms underlying VNO-mediated behavioral output

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