Pregnancy Changes the Response of the Vomeronasal and Olfactory Systems to Pups in Mice

Abstract

Motherhood entails changes in behavior with increased motivation for pups, induced in part by pregnancy hormones acting upon the brain. This work explores whether this alters sensory processing of pup-derived chemosignals. To do so, we analyse the expression of immediate early genes (IEGs) in the vomeronasal organ (VNO; Egr1) and centers of the olfactory and vomeronasal brain pathways (cFos) in virgin and late-pregnant females exposed to pups, as compared to buttons (socially neutral control). In pup-exposed females, we quantified diverse behaviors including pup retrieval, sniffing, pup-directed attack, nest building and time in nest or on nest, as well as time off nest. Pups induce Egr1 expression in the VNO of females, irrespective of their physiological condition, thus suggesting the existence of VNO-detected pup chemosignals. A similar situation is found in the accessory olfactory bulb (AOB) and posteromedial part of the medial bed nucleus of the stria terminalis (BSTMPM). By contrast, in the medial amygdala and posteromedial cortical amygdala (PMCo), responses to pups-vs-buttons are different in virgin and late-pregnant females, thus suggesting altered sensory processing during late pregnancy. The olfactory system also shows changes in sensory processing with pregnancy. In the main olfactory bulbs, as well as the anterior and posterior piriform cortex, buttons activate cFos expression in virgins more than in pregnant females. By contrast, in the anterior and especially posterior piriform cortex, pregnant females show more activation by pups than buttons. Correlation between IEGs expression and behavior suggests the existence of two vomeronasal subsystems: one associated to pup care (with PMCo as its main center) and another related to pup-directed aggression observed in some pregnant females (with the BSTMPM as the main nucleus). Our data also suggest a coactivation of the olfactory and vomeronasal systems during interaction with pups in pregnant females.

Becoming a mother shifts the activity of the social and motivation brain networks in mice

“…The data on behavior of late pregnant and virgin females exposed to pups (LP-P and V-P, respectively) were reported in a previous paper ( Navarro-Moreno et al., 2020 ), and a summary of the results is shown as supplemental information ( Table S1 ). In the present study, we analyzed the density of cFos immunoreactive cells in specific frames of brain centers belonging to the socio-sexual brain network ( Figures 1 and 2 ) and the centers involved in motivated behaviors ( Figure 3 ).…”

“…Therefore, differences in pup-directed behaviors and pup-induced brain activity between females can be safely attributed to the effects of pregnancy hormones but not to previous experience with pups (important in postpartum females). In fact, pups induce similar behaviors in LP and virgin female mice, except for pup-directed attacks, which are exhibited by some LP but not virgin females ( Navarro-Moreno et al., 2020 ; Table S1 ).…”

“…In addition, even pup-sensitized virgin female mice displaying frequent pup care show no nest defense ( Martín-Sánchez et al., 2015b ). These data suggest that hormones acting on the brain of females during pregnancy and postpartum (steroids and lactogens; Salais-López et al., 2017 ) contribute to changes in their response to pup stimuli, including chemosignals ( Navarro-Moreno et al., 2020 ), and other social cues, such as male pheromones ( Martín-Sánchez et al., 2015a , 2015b ). These changes promote a strong motivation to take care of pups and to defend the nest from putatively infanticide intruders.…”

“…Thus, the linear view of maternal care does not fit the widespread action of these hormones in the brain of females. In addition, recent evidence indicates that sensory centers not directly linked with the MPO also change their activity profile in response to pups during late pregnancy ( Navarro-Moreno et al., 2020 ). However, how and where the combined action of lactogens (placental and hypophyseal, e.g.…”

Inhibition of the medial amygdala disrupts escalated aggression in lactating female mice after repeated exposure to male intruders

“…The changes in the behavioural responses of females likely involve plastic changes of the sociosexual brain circuits, which could result from a mixture of endocrine agents and sensory inputs (chemosignals, nipple stimulation, etc.) acting during pregnancy, parturition and lactation 6,9,14,17,20,21 .…”