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The early social environment has a profound impact on developmental trajectories. Although an impoverished early environment can undermine the acquisition of appropriate social skills, the specific role played by the different components of an individual's early environment in building social competencies has not been fully elucidated. Here we setup an asynchronous communal nesting paradigm in mice to disentangle the influence of maternal care and early peer interactions on adult social behavior and neural systems reportedly involved in the regulation of social interactions. The asynchronous communal nesting consists of three mothers giving birth three days apart, generating three groups of pups - the Old, the Middle and the Young - all raised in a single nest from birth to weaning. We scored the amount of maternal and peer interactions received by these mice and by a fourth group reared under standard conditions. At adulthood, the four experimental groups have been investigated for social behavior in a social interaction test, i.e. facing an unfamiliar conspecific during five 20-min daily encounters, and for oxytocin receptor and brain derived neurotrophic factor (BDNF) levels. Results show that only individuals exposed to high levels of both maternal and peer interactions demonstrated elaborate adult agonistic competencies, i.e. the ability to promptly display a social status, and high BDNF levels in the hippocampus, frontal cortex and hypothalamus. By contrast, only individuals exposed to high levels of peer interactions showed enhanced adult affiliative behavior and enhanced oxytocin receptor levels in selected nuclei of the amygdala. Overall these findings indicate that early interactions with mother and peers independently shape specific facets of adult social behavior and neural systems involved in social interaction.

The early environment is crucial for brain and behavior development. In particular, social experiences involving the mother and the peers are critical in shaping the adult individual. Though animal models of psychiatric disorders have widely investigated the relevance of the mother–offspring interaction, the peer interaction has so far been rarely studied. The communal nest (CN) is an innovative experimental strategy that favors a more comprehensive investigation of the long-term effects of both components. CN is a rearing condition employed by up to 90% of mouse females in naturalistic settings and consists of a single nest where two or more mothers keep their pups together and share care-giving. In a CN, the developing pup is exposed to high levels of both maternal care and interaction with peers. At adulthood, these mice display relevant changes in bran function and behavior, including high levels of neural plasticity markers, such as BDNF, and elaborate adult social competences. Overall, on the one hand, CN is an experimental approach complementary to the ones currently used that allows to investigate how the early environment determines developmental trajectories. On the other, it may represent a strategy to improve the study of animal models of psychiatric disorders characterized by social dysfunction, such as major depression, autism and attention deficit hyperactivity disorder. Indeed, the more elaborate social competences shown by these mice at adulthood may allow to better characterize deficits in the social domain induced by genetic and/or environmental manipulations.

Early experiences produce persistent changes in behavior and brain function. Being reared in a communal nest (CN), consisting of a single nest where three mouse mothers keep their pups together and share care-giving behavior from birth to weaning, provides an highly stimulating social environment to the developing pup since both mother–offspring and peer-to-peer interactions are markedly increased. Here we show that being reared in a CN affects adult behavior of CD-1 mice in a gender-dependent fashion, with reduced depression-like responses in females and increased anxiety-like behavior in males. In particular, CN females showed higher sucrose preference at baseline condition, drinking more sweet solution compared to female mice reared in a standard laboratory condition (SN). In the isolation test, both SN and CN females showed a reduction in sucrose preference after exposure to isolation stress. However, after 24 h, only CN females significantly recovered. Finally, in the forced swim test, compared to SN, CN females spent longer time floating, a behavioral response that in the CN model has been inversely associated with display of endophenotypes of depression. With regard to the emotional response, CN males displayed an increased anxiety-like behavior in comparison to SN, spending less time in the open arms and displaying reduced head-dippings in the elevated plus-maze test. No difference was found in females. Overall, our findings show that gender and early experiences interact in modulating adult behavior. In particular, we show that early experiences modified developmental trajectories shaping adult endophenotypes of depression more markedly in females than in males.

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations.

Early experiences profoundly affect the adult coping response to stress and, consequently, adult vulnerability to psychopathologies triggered by stressing conditions, such as major depression. Though studies in animal models have demonstrated that individuals reared in different conditions are differently vulnerable to a stressor of a specific quality, no information is available as to whether such vulnerability differs when facing stressors of different qualities. To this purpose, we reared C57BL/6 male mice either in standard laboratory rearing condition (SN) or in Communal Nest (CN) condition, the latter consisting of a single nest where three mothers keep their pups together and share care-giving behavior until weaning. We scored the amount of interactions with the mother and with peers and found that CN is a form of social enrichment because both these components are significantly increased. At adulthood, we exposed SN and CN mice, for 4 weeks, to either a physical (forced swim) or a social stress (social instability). Immediately before, at week 1 and at week 4 of the stress procedure, corticosterone levels and the hedonic profile were measured. The results show that CN mice are more resilient to social stress than SN mice since they displayed no anhedonia and lower corticosterone levels. By contrast, both experimental groups were similarly vulnerable to physical stress. Overall, our results show that, in male mice, the adult vulnerability to stress changes according to the quality of the stressor, as a function of early experiences. In addition, the stressor to which CN mice are resilient is qualitatively similar to the stimuli they have experienced early on, both concerning the social domain.

During early postnatal phase, the environment deeply affects developmental trajectories through epigenetic mechanisms that control the levels of key molecules for brain function, such as neurotrophins. Indeed, it has been shown that adverse early experiences induce epigenetic modifications leading to decreased brain derived neurotrophic factor (BDNF) levels at adulthood. However, no data about the effects of enriching early experiences are available. Here we exploit the mouse Communal Nest (CN) paradigm in order to investigate the effects of a highly stimulating early social environment on BDNF epigenetic modifications and protein expression at adulthood. CN, which consists of a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions. Our results show that CN leads to high levels of histone acetylation at the BDNF gene at adulthood, which is more permissive to expression. However, such epigenetic modification is associated to increased BDNF protein expression only 1 h after an environmental challenge and not at baseline or 3 h after the challenge, suggesting that the epigenetic modifications do not affect expression under steady-state conditions but allow a fast increase in BDNF levels following stimulation. The present findings corroborate the role of epigenetic modifications in mediating the effects of the early social environment on adult brain function and behavior. In addition, these show, for the first time, an association between an epigenetic modification and a change in the rapidity of induction of protein expression, expanding the knowledge on the mechanisms by which epigenetic changes modify brain function.

Early experiences shape brain function and behavior and, consequently, vulnerability to psychopathology at adulthood. Here we exploited the mouse communal nest (CN) paradigm in order to investigate the effect of the early social environment on the emergence of endophenotypes of depression and on antidepressant efficacy at adulthood. CN, which consists in a single nest where three mothers keep their pups together and share care-giving behavior until weaning, is characterized by high levels of maternal behavior and peer interactions, thus representing an highly stimulating environment. Our results show that, when compared to mice reared in standard laboratory conditions (SN), adult CN mice exhibited greater sucrose preference on the first days of the test, displayed reduced anhedonia during social stress and had lower corticosterone levels after acute and prolonged social stress. Furthermore, in line with previous work, CN displayed longer immobility than SN mice in the forced swim test. Here we show that such behavioral response is differently affected by antidepressants according to early experiences. A 3-week fluoxetine treatment affected only SN mice, leading to an increase of immobility duration up to the levels showed by CN mice, while acute fluoxetine administration decreased immobility duration in both groups. These results show that being reared in a CN profoundly changes developmental trajectories, reducing the adult display of endophenotypes of depression and modifying response to antidepressants. The present findings suggest that early experiences represent one of those factors to be taken into account to identify the appropriate individual pharmacological strategy to treat depression in patients.

The interactions with the mother and with peers are among the most relevant early environmental factors shaping adult brain function and behavior. In order to investigate the role of these factors, we exploited a novel early manipulation, the Communal Nest (CN), consisting in a single nest where three mothers give birth, keep their pups and share care-giving behavior from birth to weaning. In particular, we reared CD-1 swiss mice in three different CN conditions, each one characterized by a different interval between the three deliveries (Birth Spacing) of 3, 5 or 7 days (respectively, CN ± 3, CN ± 5, CN ± 7). Length of birth spacing affected maternal behavior, CN ± 7 pups receiving the highest levels. At adulthood, mice reared in the different conditions showed differences in emotional response and social skills. In the plus maze test, short birth spacing was found to be associated with enhanced emotionality, CN ± 3 mice showing highest levels of anxiety-like responses in the plus maze compared to the other two CN groups. In the social interaction test, the strategies to achieve dominance differed among the three groups. While CN ± 3 mice appeared to have a more aggressive strategy, displaying high levels of attack behavior in the first encounter, CN ± 5 and CN ± 7 mice displayed a more affiliative strategy based on social investigation. Overall, these findings show that birth spacing shapes the early mouse social environment and, in turn, affects the development of social skills and emotional responses.

We exposed mouse pups to an early social enrichment, the communal nest (CN), to study the effects of the early social experiences on adult brain function and behavior. CN, which consists of a single nest where three mothers keep their pups together and share care-giving behavior from birth to weaning (postnatal day 25), mimics the natural ecological niche of the mouse species. In order to better characterize the previously reported effect of CN on social behavior and to evaluate the extent to which the effects of the CN tend to be pervasive across different behavioral competences, we carried out both a detailed analysis of home-cage social behavior, taking into account the time of the day and absence/presence of an established social hierarchy, and of learning and memory abilities in the water maze. Home-cage observations revealed that, when the hierarchy is established, CN mice display higher levels of social investigation behavior, namely allogrooming and allosniffing, compared to mice reared in standard laboratory conditions (SN). However, when exposed to cage cleaning, a stimulus challenging social hierarchy, CN mice display higher levels of offensive behavior. In the water maze test, CN mice showed a performance similar to that of SN mice. Overall, the present findings confirm that CN mice have elaborate social competencies displaying high levels of aggressive behavior when needed to set up or defend their own territory. Furthermore, present data suggest that the early social enrichment specifically affect adult social behavior but not learning and memory abilities.