Peripheral oxytocin injection modulates vomeronasal sensory activity and reduces pup-directed aggression in male mice

Thiago S Nakahara,Vinicius M A Carvalho,Antonio P Camargo,Paulo H Martins-Netto,Fabio Papes,Mateus A A Souza,Pedro G Ribeiro,Pedro H M Magalhães,Juliana José

doi:10.1038/s41598-020-77061-7

Thiago S Nakahara, Vinicius M A Carvalho + Show 7 more

Open Access

https://doi.org/10.1038/s41598-020-77061-7

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Journal: Scientific Reports	Publication Date: Nov 17, 2020
Citations: 15	License type: open-access

Affiliation: Universidade Estadual de Campinas

Abstract

Behaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues. Pup-directed behaviors have been previously shown to change via action of hormones at the brain level. Here, we investigated hormonal control of pup-induced activity in the vomeronasal organ, an olfactory sensory structure involved in the detection of non-volatile chemosignals. Vomeronasal activity decreases as males switch from a pup-aggressive state to a non-aggressive parenting state, after they socially contact a female. RNA sequencing, qPCR, and in situ hybridization were used to identify expression, in the vomeronasal sensory epithelium, of candidate GPCR hormone receptors chosen by in silico analyses and educated guesses. After identifying that oxytocin and vasopressin receptors are expressed in the vomeronasal organ, we injected the corresponding hormones in mice and showed that oxytocin administration reduced both pup-induced vomeronasal activity and aggressive behavior. Conversely, injection of an oxytocin receptor antagonist in female-primed male animals, which normally exhibit reduced vomeronasal activity, significantly increased the number of active vomeronasal neurons. These data link oxytocin to the modulation of olfactory sensory activity, providing a possible mechanism for changes in male behavior after social experience with females.

Highlights

Behaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues
We screened a large number of G-protein coupled receptors (GPCR) receptors that may function as hormone receptors, looking for the expression of these candidates in an olfactory organ known to be involved in the control of pup-driven behavior, the vomeronasal o rgan[34,35,42,69] (Table 1 and Supplementary Tables S2, S3)
Of those found in the vomeronasal organ (VNO) by in situ labeling, some exhibited preferential spatial expression in the basal VNO zone (Fig. 2), which does not harbor most of the pup-responsive cells

Summary

Introduction

Behaviors are shaped by hormones, which may act either by changing brain circuits or by modifying sensory detection of relevant cues. Oxytocin modulates nurturing behaviors in mother a nimals[11], while vasopressin controls scent marking, aggressive behavior, and offspring care exhibited by fathers[12,13,14,15,16,17] These effects seem to be commanded by hormonal action at the brain level, since intracerebral oxytocin injection in pregnant mice increases maternal b ehavior[18], whereas administration of oxytocin receptor antagonists impairs maternal behavior[19,20,21]. Administration of oxytocin receptor antagonist led to an increase in pup-induced VNO activity Together, these data strongly suggest that vomeronasal neurons sense the individual’s oxytocin levels to change sensory neuron activity. We hypothesize that this phenomenon may mediate changes in pupdriven behaviors

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