Active defense against a conspecific aggressor is essential for survival. Previous studies revealed strong c-Fos expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl) in ...defeated animals. Here, we examined the functional relevance and in vivo responses of the VMHvl during conspecific defense. We found that VMHvl cells expressing estrogen receptor α (Esr1) are acutely excited during active conspecific defense. Optogenetic inhibition of the cells compromised an animal’s ability to actively defend against an aggressor, whereas activating the cells elicited defense-like behaviors. Furthermore, the VMHvl is known for its role in aggression. In vivo recording and c-Fos mapping revealed differential organization of the defense and aggression-responsive cells in the VMHvl. Specifically, defense-activated cells are concentrated in the anterior part of the VMHvl, which preferentially targets the periaqueductal gray (PAG). Thus, our study identified an essential neural substrate for active conspecific defense and expanded the function of the VMHvl.
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•VMHvl, especially its anterior part, is highly excited during active social defense•Inhibiting the VMHvl Esr1+ cells compromises active defense against an aggressor•Activating the anterior VMHvl Esr1+ cells elicits defense-like behaviors•Anterior and posterior VMHvl Esr1+ cells show differential projection patterns
Active defense against conspecific aggressors is essential for survival, but its underlying neural substrates remain largely unknown. Through a series of in vivo recordings and functional manipulations, Wang et al. demonstrate that cells expressing estrogen receptor α in a small medial hypothalamic nucleus are essential for defense against a bully.
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.
Mating drive is balanced by a need to safeguard resources for offspring, yet the neural basis for negative regulation of mating remains poorly understood. In rodents, pheromones critically regulate ...sexual behavior. Here, we observe suppression of adult female sexual behavior in mice by exocrine gland-secreting peptide 22 (ESP22), a lacrimal protein from juvenile mice. ESP22 activates a dedicated vomeronasal receptor, V2Rp4, and V2Rp4 knockout eliminates ESP22 effects on sexual behavior. Genetic tracing of ESP22-responsive neural circuits reveals a critical limbic system connection that inhibits reproductive behavior. Furthermore, V2Rp4 counteracts a highly related vomeronasal receptor, V2Rp5, that detects the male sex pheromone ESP1. Interestingly, V2Rp4 and V2Rp5 are encoded by adjacent genes, yet couple to distinct circuits and mediate opposing effects on female sexual behavior. Collectively, our study reveals molecular and neural mechanisms underlying pheromone-mediated sexual rejection, and more generally, how inputs are routed through olfactory circuits to evoke specific behaviors.
Sexual imprinting is important for kin recognition and for promoting outbreeding, and has been a driving force for evolution; however, little is known about sexual imprinting by auditory cues in ...mammals. Male mice emit song-like ultrasonic vocalizations that possess strain-specific characteristics.
In this study, we asked whether female mice imprint and prefer specific characteristics in male songs.
We used the two-choice test to determine the song preference of female C57BL/6 and BALB/c mice. By assessing the time engaged in searching behavior towards songs played back to females, we found that female mice displayed an innate preference for the songs of males from different strains. Moreover, this song preference was regulated by female reproductive status and by male sexual cues such as the pheromone ESP1. Finally, we revealed that this preference was reversed by cross-fostering and disappeared under fatherless conditions, indicating that the behavior was learned by exposure to the father's song.
Our results suggest that female mice can discriminate among male song characteristics and prefer songs of mice from strains that are different from their parents, and that these preferences are based on their early social experiences. This is the first study in mammals to demonstrate that male songs contribute to kin recognition and mate choice by females, thus helping to avoid inbreeding and to facilitate offspring heterozygosity.
The Bruce effect refers to pregnancy termination in recently pregnant female rodents upon exposure to unfamiliar males 1. This event occurs in specific combinations of laboratory mouse strains via ...the vomeronasal system 2, 3; however, the responsible chemosensory signals have not been fully identified. Here we demonstrate that the male pheromone exocrine gland-secreting peptide 1 (ESP1) is one of the key factors that causes pregnancy block. Female mice exhibited high pregnancy failure rates upon encountering males that secreted different levels of ESP1 compared to the mated male. The effect was not observed in mice that lacked the ESP1 receptor, V2Rp5, which is expressed in vomeronasal sensory neurons. Prolactin surges in the blood after mating, which are essential for maintaining luteal function, were suppressed by ESP1 exposure, suggesting that a neuroendocrine mechanism underlies ESP1-mediated pregnancy failure. The single peptide pheromone ESP1 conveys not only maleness to promote female receptivity but also the males’ characteristics to facilitate memorization of the mating partner.
•Strain-specific differences in ESP1 secretion contribute to the Bruce effect•ESP1 induced prolactin surge blockade in recipient females during pregnancy•ESP1 both enhances sexual behavior and changes the endocrine status in females
Hattori et al. reveal that the male mouse pheromone ESP1 is a signaling molecule responsible for the pregnancy block. The female mated with a male memorizes the amount of ESP1 from the partner as an individual signature. Differences in the amount of ESP1 inhibit prolactin release and induce pregnancy block.
Exocrine gland-secreting peptide 1 (ESP1) released into male tear fluids is a male pheromone that stimulates sexually receptive behavior in female mice via the vomeronasal sensory system. ESP1 also ...induces c-Fos expression in male brain regions distinct from those in females. However, behavior in males following ESP1 exposure has not been examined. In the present study, we show that ESP1, in conjunction with unfamiliar male urine, enhances male aggression via the specific vomeronasal receptor V2Rp5. In addition, male mice that secrete ESP1 but lack V2Rp5 exhibit a lower level of aggressiveness than do mice that express V2Rp5. These results suggest that ESP1 not only acts as a male pheromone in both sexes but also serves as an auto-stimulatory factor that enhances male aggressiveness by self-exposure. Finally, re-activation of ESP1-induced c-Fos-positive neurons by using the designer receptor exclusively activated by designer drug (DREADD) approach resulted in enhancement of sexual and aggressive behaviors in female and male mice, respectively, indicating that sexually dimorphic activation in the brain is a neural basis for the sex-specific behavioral responses to ESP1.
•ESP1 in male mouse tears enhances aggression in recipients in conjunction with urine•Self-secreted ESP1 auto-stimulates aggressiveness in males•Reactivation of ESP1-induced c-Fos in neurons by DREADDs was sexually dimorphic•The reactivation by DREADDs reproduced the sex-specific behavioral response to ESP1
Sexual cues directly trigger ritualistic behavioral sequences mediated by pre-programmed neural circuits. Hattori et al. demonstrate that male mouse pheromone ESP1 stimulates male aggression and female sexual behavior via sex-specific neural activation. ESP1 also acts as an auto-stimulatory factor enhancing aggression through self-exposure.
Male mice emit ultrasonic vocalizations (USVs) in response to the presence of female mice and their urine. Male USVs attract females, enhancing female reproductive functions, and are thus considered ...as the courtship song. Previous studies have shown that female mice exhibit disassortative social preferences for male USVs. However, it remains unclear what acoustic features female mice use for the development of these preferences. To address this, we examined social preferences of female C57BL/6 and BALB/c mice using the three-chamber preference test using recorded male USVs. To dissociate the peak frequencies of these USVs from their syllable structure, we digitally manipulated the peak frequencies accordingly. We found that female mice preferred USVs that were dissimilar to those of their own strain. We also observed that, while female C57BL/6 mice were sensitive to changes in the syllable structure and the peak frequency, female BALB/c mice were sensitive to differences in the syllable structure. Our results demonstrate that female C57BL/6 and BALB/c mice differently use the acoustic features such as the peak frequency and the syllable structure for exhibiting disassortative social preferences.
Sensory signals are critical to perform adaptive social behavior. During copulation, male mice emit ultrasonic vocalizations (USVs). Our previous studies have shown that female mice exhibit approach ...behavior toward sound sources of male USVs and that, after being exposed to a male pheromone, exocrine gland-secreting peptide 1 (ESP1), female mice exhibited a preference toward a particular type of male USVs. These findings suggest that male USVs modulate female courtship behavior. However, it remains unclear which brain regions and what cell types of neurons are involved in neuronal processing of male USVs. To clarify this issue, immediate early gene analysis, behavioral analysis, and neurochemical analysis were performed. The
hybridization analysis of
mRNA in multiple brain regions showed that neurons in the prelimbic cortex were responsive to presentation of male USVs in the presence of ESP1. Furthermore, this study found that activity of prelimbic cortex was correlated with the duration of female exploration behavior toward a sound source of the USVs. Finally, by using double immunohistochemistry, the present study showed that the prelimbic neurons responding to the presentation of male USVs were presumably excitatory glutamatergic neurons. These results suggest that the prelimbic cortex may facilitate female courtship behavior in response to male USVs.
Hypothalamic control of innate social behaviors Mei, Long; Osakada, Takuya; Lin, Dayu
Science (American Association for the Advancement of Science),
10/2023, Volume:
382, Issue:
6669
Journal Article
Peer reviewed
Sexual, parental, and aggressive behaviors are central to the reproductive success of individuals and species survival and thus are supported by hardwired neural circuits. The reproductive behavior ...control column (RBCC), which comprises the medial preoptic nucleus (MPN), the ventrolateral part of the ventromedial hypothalamus (VMHvl), and the ventral premammillary nucleus (PMv), is essential for all social behaviors. The RBCC integrates diverse hormonal and metabolic cues and adjusts an animal's physical activity, hence the chance of social encounters. The RBCC further engages the mesolimbic dopamine system to maintain social interest and reinforces cues and actions that are time-locked with social behaviors. We propose that the RBCC and brainstem form a dual-control system for generating moment-to-moment social actions. This Review summarizes recent progress regarding the identities of RBCC cells and their pathways that drive different aspects of social behaviors.
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