Francesca R. D'Amato

Ultrasonic vocalizations emitted during dyadic interactions in female mice : A possible index of sociability?

Despite the evidence that ultrasonic vocalizations are a consistent component of the behavioural repertoire of female mice, only few studies have investigated this phenomenon. In this paper, we reported new data about ultrasonic vocalisations emitted during female-female mice social encounters. In particular, we first showed that the resident female utters a considerable number of 70 kHz calls and that the number of calls seems to be modulated by the motivational state of the emitter during the estrous cycle: sexually receptive females emitted fewer ultrasonic vocalizations than non-receptive ones in the presence of a female intruder. A strong positive correlation linked the number of calls and the time spent by the resident sniffing the intruder female. Moreover, the number of calls uttered during interaction with an unknown female partner significantly decreased with pregnancy and ageing. Secondly we reported that 1-year-old female mice showed a reduction of ultrasonic calls in the presence of a partner they had been exposed to, only if the re-exposure (test) occurred 30 min after the previous presentation. If the test was performed with a delay of 60 min, the number of calls emitted did not decrease. These results confirm that ultrasonic vocalizations emitted during social interaction with a female conspecific can be used as an index of social recognition and can be useful to detect age-related disruption of social memory in female mice.

Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice.

Background No animal models of autism spectrum disorders (ASD) with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6), which may explain some of the conflicting results that have been obtained with these mutants up till now. Methods Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors), as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events). Results Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. Conclusions The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes.

Anxiety and maternal aggression in house mice (Mus musculus): a look at interindividual variability.

The hypotheses were tested that mouse motherhood is accompanied by decreased reactivity to aversive stimuli and that female anxiety is inversely related to the probability of displaying intense forms of postpartum aggression. Outbred Swiss female mice were tested for anxiety in a light/dark choice test when virgin, pregnant, or lactating, and then tested for maternal aggression (5-min exposure to a male intruder) on postpartum Day 7. Anxiety declined in pregnant and lactating females when compared with virgin animals. Furthermore, females who displayed higher scores of postpartum fighting were less anxious in the previous test regardless of reproductive stage. Part of interindividual variability in postpartum aggression might thus be related to differences in the extent to which individuals perceive and react to anxiogenic situations. In addition, the higher emotionality characterizing the C57BL/6 and DBA/2 inbred strains may be responsible for the lack of a clear-cut exhibition of maternal aggression in these two strains.

Ultrasonic vocalizations as an index of social memory in female mice.

Ultrasonic vocalization (UV) as a measure of social memory was investigated in female mice. UVs emitted by a resident female in the presence of a same-sex partner were measured during a 3-min, pretest social interaction. In a second 3-min test session, mice were reexposed to the familiar partner or presented with a novel partner. In the first case, there was a decline in UVs emitted by resident mice when the intervals between the 2 sessions were 15, 30, or 60 min. After 24 hr, this effect disappeared. In contrast, with a novel female partner, the number of UVs remained unchanged. Scopolamine (0.05 mg/kg ip) disrupted this memory process: Drug-treated females did not show the expected decrease in UVs when reexposed to the familiar female after 30 min. This study provides behavioral and pharmacological evidence that ultrasonic calls can be used as a measure of social memory in female mice.

Chronic social stress, hedonism and vulnerability to obesity: Lessons from Rodents

Obesity is a current health pandemia. Determinants of this pathology are rather complex and include genetic, developmental and environmental factors only partially disclosed. Stress related neuroendocrine dysregulation and overconsumption of high palatable high caloric food and are likely to contribute to this modern health threats. Despite the evidence that psychosocial stress is one of the main sources of stress in humans and may play an important role in the development of the stress disorders, including obesity and metabolic syndrome, animal models focusing on the relationship between chronic stress and energy homeostasis are scattered and most of them encompasses physical rather than psychosocial stress. Aim of the present paper is to review rodent studies on the effect of psychosocial stress throughout life on body weight and food intake regulation. In the second part of the review special focus will be given on the mechanisms linking stress and the reward system.

Unstable maternal environment, separation anxiety, and heightened CO2 sensitivity induced by gene-by-environment interplay

Background In man, many different events implying childhood separation from caregivers/unstable parental environment are associated with heightened risk for panic disorder in adulthood. Twin data show that the occurrence of such events in childhood contributes to explaining the covariation between separation anxiety disorder, panic, and the related psychobiological trait of CO2 hypersensitivity. We hypothesized that early interference with infant-mother interaction could moderate the interspecific trait of response to CO2 through genetic control of sensitivity to the environment. Methodology Having spent the first 24 hours after birth with their biological mother, outbred NMRI mice were cross-fostered to adoptive mothers for the following 4 post-natal days. They were successively compared to normally-reared individuals for: number of ultrasonic vocalizations during isolation, respiratory physiology responses to normal air (20%O2), CO2-enriched air (6% CO2), hypoxic air (10%O2), and avoidance of CO2-enriched environments. Results Cross-fostered pups showed significantly more ultrasonic vocalizations, more pronounced hyperventilatory responses (larger tidal volume and minute volume increments) to CO2-enriched air and heightened aversion towards CO2-enriched environments, than normally-reared individuals. Enhanced tidal volume increment response to 6%CO2 was present at 16–20, and 75–90 postnatal days, implying the traits stability. Quantitative genetic analyses of unrelated individuals, sibs and half-sibs, showed that the genetic variance for tidal volume increment during 6%CO2 breathing was significantly higher (Bartlett χ = 8.3, p = 0.004) among the cross-fostered than the normally-reared individuals, yielding heritability of 0.37 and 0.21 respectively. These results support a stress-diathesis model whereby the genetic influences underlying the response to 6%CO2 increase their contribution in the presence of an environmental adversity. Maternal grooming/licking behaviour, and corticosterone basal levels were similar among cross-fostered and normally-reared individuals. Conclusions A mechanism of gene-by-environment interplay connects this form of early perturbation of infant-mother interaction, heightened CO2 sensitivity and anxiety. Some non-inferential physiological measurements can enhance animal models of human neurodevelopmental anxiety disorders.

Scratching as a behavioral index of anxiety in macaque mothers

The aim of this study was to assess the validity of the notion that anxiety influences maternal style in monkeys. To this end, we investigated the correlations between measures of the quality of mother-infant relationship and scratching, a behavior pattern that reflects a state of anxiety. The subjects were seven group-living macaque mothers and their infants observed during the first 12 weeks postpartum. Postpartum scratching by the mothers was positively correlated with both maternal possessiveness and maternal warmth, two composite measures of the quality of mother-infant relationship that reflect a possessive and attentive maternal style. Evaluation of the correlations between maternal rank and scratching before and after parturition indicated that interactions with their infants, not those with other group companions, were the main source of anxiety for the mothers. These results support the notion that anxiety influences maternal style in monkeys and suggest that studies aimed at investigating physiological and social correlates of maternal emotionality in nonhuman primates could use scratching as a useful and simple behavioral measure.

Effects of postnatal stress on dopamine mesolimbic system responses to aversive experiences in adult life

The effects of postnatal stress on mesolimbic dopamine (DA) functioning in 90-day-old mice were investigated. Postnatal stress consisted of 15 min daily exposure to clean bedding (CB) in the absence of the mother for the first two weeks of life. Controls were daily exposed to home cage bedding (HCB) in the absence of the mother. A single brief (5-10 min) exposure to restraint produced a clear-cut increase in DA metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT)) in the nucleus accumbens septi (NAS) of adult HCB but not CB mice. Moreover, when tested in an elevated plus maze, CB mice showed more exploration and reduced fearfulness in comparison with HCB mice. Taken together, these results indicate reduced emotional reactivity in adult mice repeatedly stressed during postnatal development. Moreover, HCB mice but not CB mice showed altered behavioral responsiveness to apomorphine following repeated restraint stress (10 daily 120 min) in adult life, although no difference in the behavioral response to either a low or a high dose of apomorphine was observed in adult unstressed mice of the CB and HCB groups. These results indicate that the effects of early experiences on brain DA functioning may not be evident in basal conditions and be revealed only under environmental pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic exposure to a novel odor increases pups' vocalizations, maternal care, and alters dopaminergic functioning in developing mice.

This study was designed to assess the stress effect of manipulation of the olfactory environment in developing mice. In a first experiment it was found that mouse pups could be stressed (as measured by an increase in ultrasonic calls) by removing the litter from the dam for 15 min/day for the first 14 days of life and exposing them to a novel odor (clean bedding). This stress procedure also produced a long-term modification in maternal behavior. The stress response (ultrasounds) and the modification of maternal behavior were prevented by providing the litter with home cage bedding during maternal separation. In a second experiment it was demonstrated that early stress influenced apomorphine-induced wall climbing behavior in 15-day-old mice, suggesting stress-induced alterations in the dopaminergic system. Pups exposed to clean bedding during infancy exhibited more wall climbing behavior than pups never separated from the mother. Moreover, preventing the early stress response during mother-offspring separation, by providing pups with home cage bedding, eliminated the increase in apomorphine-induced wall climbing. Taken together these results suggest that olfactory cues are decisive in characterizing stressful situations inducing both immediate and long-lasting effects in mouse pups.

Endogenous opioids: a proximate reward mechanism for kin selection?

The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Proximate mechanisms have been postulated to exist helping the individual to discriminate what is good or bad for him. Opioids have been discovered to be involved in the mediation of reinforcement, in particular they underlay social emotion. In this study it is shown that pain sensitivity decreased in male mice interacting with siblings following 2 months of separation; this analgesic response was antagonized by naloxone administration. Interaction with unknown and unrelated subjects did not change the nociceptive threshold. These results suggest that interacting with kin is an adaptive situation reinforced, at the neural level, by the release of endogenous opioids.