Regulation Of Social Behavior Research Articles

Huddling substates in mice facilitate dynamic changes in body temperature and are modulated by Shank3b and Trpm8 mutation.

Social thermoregulation is a means of maintaining homeostatic body temperature. While adult mice are a model organism for studying both social behavior and energy regulation, the relationship between huddling and core body temperature (Tb) is poorly understood. Here, we develop a behavioral paradigm and computational tools to identify active-huddling and quiescent-huddling as distinct thermal substates. We find that huddling is an effective thermoregulatory strategy in female but not male groups. At 23°C (room temperature), but not 30°C (near thermoneutrality), huddling facilitates large reductions in Tb and Tb-variance. Notably, active-huddling is associated with bidirectional changes in Tb, depending on its proximity to bouts of quiescent-huddling. Further, group-housed animals lacking the synaptic scaffolding gene Shank3b have hyperthermic Tb and spend less time huddling. In contrast, individuals lacking the cold-sensing gene Trpm8 have hypothermic Tb - a deficit that is rescued by increased huddling time. These results reveal how huddling behavior facilitates acute adjustments of Tb in a state-dependent manner.

Sex differences in the structure and function of the vasopressin system in the ventral pallidum are associated with the sex-specific regulation of social play behavior in juvenile rats

Vasopressin (AVP) regulates various social behaviors, often in sex-specific ways, including social play behavior, a rewarding behavior displayed primarily by juveniles. Here, we examined whether and how AVP acting in the brain's reward system regulates social play behavior in juvenile rats. Specifically, we focused on AVP signaling in the ventral pallidum (VP), a brain region that is a part of the reward system. First, we examined the organization of the VP-AVP system in juvenile rats and found sex differences, with higher density of both AVP-immunoreactive fibers and AVP V1a receptor (V1aR) binding in males compared to females while females show a greater number of V1aR-expressing cells compared to males. We further found that, in both sexes, V1aR-expressing cells co-express a GABA marker to a much greater extent (approx. 10 times) than a marker for glutamate. Next, we examined the functional involvement of V1aR-expressing VP cells in social play behavior. We found that exposure to social play enhanced the proportion of activated V1aR-expressing VP cells in males only. Finally, we showed that infusion of a specific V1aR antagonist into the VP increased social play behaviors in juvenile male rats while decreasing these behaviors in juvenile female rats. Overall, these findings reveal structural and functional sex differences in the AVP-V1aR system in the VP that are associated with the sex-specific regulation of social play behavior.

Effects of Arginine-vasopressin in the Brain on Social Behavior and Communication in a Psychosocial Stress Animal Model

Psychosocial stressors (e.g., anxiety, personality traits, social isolation) are risk factors for negative health outcomes, including cardiovascular disease and neuropsychiatric disorders. However, there is a knowledge gap regarding the biological mechanisms that underlie these risk-outcome relationships. To address this gap, our team uses the Syrian hamster ( Mesocricetus auratus) as an animal model for investigating psychosocial behaviors and stress responses. Our previous findings and work reported by others indicate that the neuropeptide arginine-vasopressin (AVP) acts in the brain to regulate the expression of social behavior and communication. In the present study, stereotaxic surgeries were used to cannulate six adult hamsters (1 female, 5 males) with cannulae aimed at different forebrain regions, mostly focusing on hypothalamic areas. Cannulated animals were microinjected with 200 nl of a 9 μM AVP solution and saline in counterbalanced order with a 4-day inter-test interval. Three of the six animals displayed a type of social communication behavior called flank marking in response to AVP, whereas none of the animals flank marked in response to saline; these group differences were statistically significant (χ2 (1, N=6)= 4.0, p< 0.05). Previous research groups confirmed the anterior hypothalamic area (AHA) as a site of action for the effects of AVP on social behaviors. Our results suggest that, in addition to the AHA, the dorsomedial hypothalamic nucleus (DM) and posterior hypothalamic area (PH) may also be sites of action for AVP. We are currently testing the behavioral effects of AVP when microinjected into the midbrain. The preliminary findings reported here will help us identify areas of the brain that are part of a larger neural network that is involved in the regulation of social behavior and stress responses by AVP. Our long-term goal is to develop a psychosocial stress model to test the hypothesis that AVP may have therapeutic potential for psychosocial stress-associated conditions, including cardiovascular disease and neuropsychiatric disorders. This research is supported by NIH grant #5K01HL145339-03 (PI: M. Gil). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Psychostimulants and social behaviors.

Mounting evidence from animal models and human studies indicates that psychostimulants can significantly affect social behaviors. This is not surprising considering that the neural circuits underlying the regulation and expression of social behaviors are highly overlapped with those targeted by psychostimulants, which in most cases have strong rewarding and, consequently, addictive properties. In the present work, we provide an overview regarding the effects of illicit and prescription psychostimulants, such as cocaine, amphetamine-type stimulants, methylphenidate or modafinil, upon social behaviors such as social play, maternal behavior, aggression, pair bonding and social cognition and how psychostimulants in both animals and humans alter them. Finally, we discuss why these effects can vary depending on numerous variables such as the type of drug considered, acute versus long-term use, clinical versus recreational consumption, or the presence or absence of concomitant risk factors.

Long-range projections of oxytocin neurons in the marmoset brain.

The neurohormone oxytocin (OT) has become a major target for the development of novel therapeutic strategies to treat psychiatric disorders such as autism spectrum disorder because of its integral role in governing many facets of mammalian social behavior. Whereas extensive work in rodents has produced much of our knowledge of OT, we lack basic information about its neurobiology in primates making it difficult to interpret the limited effects that OT manipulations have had in human patients. In fact, previous studies have revealed only limited OT fibers in primate brains. Here, we investigated the OT connectome in marmoset using immunohistochemistry, and mapped OT fibers throughout the brains of adult male and female marmoset monkeys. We found extensive OT projections reaching limbic and cortical areas that are involved in the regulation of social behaviors, such as the amygdala, the medial prefrontal cortex, and the basal ganglia. The pattern of OT fibers observed in marmosets is notably similar to the OT connectomes described in rodents. Our findings here contrast with previous results by demonstrating a broad distribution of OT throughout the marmoset brain. Given the prevalence of this neurohormone in the primate brain, methods developed in rodents to manipulate endogenous OT are likely to be applicable in marmosets.

Self Directed Learning Scale at University Context

This research was carried out to investigate a relationship between self-directedness, self-involvement, expressive language, self-assessment, language varieties, metacognitive skills, editing and problem solving, text processing, knowledge rehearsal, idea planning, goal oriented monitoring and evaluating, peer learning, feedback handling, interest enhancement, motivational self-talk, and emotional control and the main and forming factors of self-directedness, self-involvement, expressive language, self-assessment, language varieties, metacognitive skills, editing and problem solving, text processing, knowledge rehearsal, idea planning, goal oriented monitoring and evaluating, peer learning, feedback handling, interest enhancing, motivational self-talk, and emotional control of self directed learning. A convenience sample approach was used to recruit English majors from a range of State University of Yogyakarta. All participants were recruited intentionally, and that they were informed that they might leave the study at any moment either during collecting data. The participant criteria include second-year English major students from various State Universities of Yogyakarta. As the result of pearson correlation in this research, it was found that there was a substantial relationship between the variables examined in this research. Moreover, as the result of factor analysis in this research was found that from the 11 variables included in the research namely self involvement, expressive language, self assessment, language varieties, metacognitive skills, editing and problem solving, Cognition, Metacognition, Social Behavior, and Motivational Regulation, they can be grouped into two main factors. The implications of these findings lie in a deeper understanding of the underlying conceptual structure of self-directed learning in a university context. With the identification of the key factors emerging from these variables, a more focused approach can be developed to enhance students' self-directed learning. This can also aid in the development of more precise and measurable assessment instruments to gauge progress in crucial aspects of self-directed learning. Thus, the implications of these findings can enrich teaching and learning practices in higher education settings.

Correlated signatures of social behavior in cerebellum and anterior cingulate cortex.

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

Correlated signatures of social behavior in cerebellum and anterior cingulate cortex

The cerebellum has been implicated in the regulation of social behavior. Its influence is thought to arise from communication, via the thalamus, to forebrain regions integral in the expression of social interactions, including the anterior cingulate cortex (ACC). However, the signals encoded or the nature of the communication between the cerebellum and these brain regions is poorly understood. Here, we describe an approach that overcomes technical challenges in exploring the coordination of distant brain regions at high temporal and spatial resolution during social behavior. We developed the E-Scope, an electrophysiology-integrated miniature microscope, to synchronously measure extracellular electrical activity in the cerebellum along with calcium imaging of the ACC. This single coaxial cable device combined these data streams to provide a powerful tool to monitor the activity of distant brain regions in freely behaving animals. During social behavior, we recorded the spike timing of multiple single units in cerebellar right Crus I (RCrus I) Purkinje cells (PCs) or dentate nucleus (DN) neurons while synchronously imaging calcium transients in contralateral ACC neurons. We found that during social interactions a significant subpopulation of cerebellar PCs were robustly inhibited, while most modulated neurons in the DN were activated, and their activity was correlated with positively modulated ACC neurons. These distinctions largely disappeared when only non-social epochs were analyzed suggesting that cerebellar-cortical interactions were behaviorally specific. Our work provides new insights into the complexity of cerebellar activation and co-modulation of the ACC during social behavior and a valuable open-source tool for simultaneous, multimodal recordings in freely behaving mice.

Neonatal treatment with para-chlorophenylalanine (pCPA) induces adolescent hyperactivity associated with changes in the paraventricular nucleus Crh and Trh expressions

Disruption of the brain serotoninergic (5-HT) system during development induces long-lasting changes in molecular profile, cytoarchitecture, and function of neurons, impacting behavioral regulation throughout life. In male and female rats, we investigate the effect of neonatal tryptophan hydroxylase (TPH) inhibition by using para-chlorophenylalanine (pCPA) on the expression of 5-HTergic system components and neuropeptides related to adolescent social play behavior regulation. We observed sex-dependent 5-HT levels decrease after pCPA-treatment in the dorsal raphe nucleus (DRN) at 17 and 35 days. Neonatal pCPA-treatment increased playing, social and locomotory behaviors assessed in adolescent rats of both sexes. The pCPA-treated rats demonstrated decreased Crh (17 days) and increased Trh (35 days) expression in the hypothalamic paraventricular nucleus (PVN). There was sex dimorphism in Htr2c (17 days) and VGF (35 days) in the prefrontal cortex, with the females expressing higher levels of it than males. Our results indicate that neonatal pCPA-treatment results in a long-lasting and sex-dependent DRN 5-HT synthesis changes, decreased Crh, and increased Trh expression in the PVN, resulting in a hyperactivity-like phenotype during adolescence. The present work demonstrates that the impairment of TPH function leads to neurobehavioral disorders related to hyperactivity and impulsivity, such as attention deficit hyperactivity disorder (ADHD).

The Multifaceted Role of Oxytocinergic System and OXTR Gene.

The article explores the multifaceted role of the neuropeptide oxytocin in human behavior and its connection to the oxytocin receptor ( OXTR ) gene. Oxytocin, produced in specific brain nuclei, is implicated in emotional, social, and maternal behaviors, stress reduction, uterine contraction during childbirth, and lactation. The OXTR gene, located on chromosome 3, encodes oxytocin receptors found in various body parts, including critical brain regions associated with social behaviors. The article delves into studies on rodents, revealing correlations between OXTR gene expression and pair bonding in the prefrontal cortex and social behavior regulation in the amygdala. The discussion extends to the impact of oxytocin on social support-seeking behavior, focusing on a specific genetic variation, rs53576. The article explores how this genetic variation influences empathy, stress reactivity, and susceptibility to disorders such as autism and social anxiety. Furthermore, the article examines structural and functional changes in the brain associated with OXTR gene variations. It discusses the role of DNA methylation in influencing oxytocin receptor availability, affecting social perception and responsiveness to negative stimuli. The article also highlights the oxytocinergic system's involvement in disorders such as autism and social anxiety, emphasizing the interplay between genetics and environmental factors. The article also touches on the potential therapeutic use of exogenous oxytocin in mitigating symptoms associated with these disorders. In summary, the article underscores the intricate relationship between oxytocin, the OXTR gene, and diverse aspects of human behavior, providing insights into social bonding, perception, and the development of behavioral disorders.

Estrogen Receptor β in the Lateral Septum Mediates Estrogen Regulation of Social Anxiety-like Behavior in Male Mice

17β-estradiol (E2) regulates various forms of social behavior through the activation of two types of estrogen receptors, ERα and ERβ. The lateral septum (LS) is thought to be one of the potential target sites of E2, but the role played by ERα and ERβ in this brain area remains largely unknown. In the present study, we first analyzed the distribution of ERα and ERβ with double fluorescent immunohistochemistry in a transgenic mouse line in which red fluorescent protein (RFP) signal has been a reliable marker of ERβ expression. The overall number of ERβ-RFP-expressing cells was significantly higher (about 2.5 times) compared to ERα-expressing cells. The distribution of the two types of ERs was different, with co-expression only seen in about 1.2% of total ER-positive cells. Given these distinctive distribution patterns, we examined the behavioral effects of site-specific knockdown of each ER using viral vector-mediated small interference RNA (siRNA) techniques in male mice. We found ERβ-specific behavioral alterations during a social interaction test, suggesting involvement of ERβ-expressing LS neurons in the regulation of social anxiety and social interest. Further, we investigated the neuronal projections of ERα- and ERβ-expressing LS cells by injecting an anterograde viral tracer in ERα-Cre and ERβ-iCre mice. Dense expression of green fluorescence protein (GFP) in synaptic terminals was observed in ERβ-iCre mice in areas known to be related to the modulation of anxiety. These findings collectively suggest that ERβ expressed in the LS plays a major role in the estrogenic control of social anxiety-like behavior.

Interpersonal distance preferences: an unexplored consequence of hearing loss

BackgroundInterpersonal distance (IPD), which reflects the physical space between people, ensures the regulation of social behavior in interaction as part of nonverbal communication. Our research aims to reveal whether there is a difference in personal distance preference between individuals with hearing loss and normal hearing (NH).MethodsThirty-five adults (26.54 ± 7.05 years) were divided into three groups according to hearing status: hearing aid (HA) users, cochlear implant (CI) users, and NH individuals. The preferred interpersonal distance scale (PIPDS) and a stop distance paradigm were employed for measurements in various environments. Personal space violations were monitored using an electrodermal activity (EDA) wristband.ResultsOur findings showed a significant relationship between preferred interpersonal distance (PID) and hearing loss duration (r = 571; p < .01) and a significant difference in PIDs between CI users and NH individuals (p = .025). There was a correlation between PIPDS results and interpersonal distance preference in two outdoor conditions where the experimenter was male. However, there was no correlation between interpersonal distance and EDA results.ConclusionsFor the CI group, PIPDS results indicated an increased interpersonal distance preference with the severity of hearing loss, possibly to enhance lip-reading cues and conceal visible hearing aids. Understanding these preferences is essential for effective communication and good interpersonal relationships among individuals with hearing loss.

Genomic Signatures of Positive Selection in Human Populations of the OXT, OXTR, AVP, AVPR1A and AVR1B Gene Variants Related to the Regulation of Psychoemotional Response.

The neurobiological systems of maintenance and control of behavioral responses result from natural selection. We have analyzed the selection signatures for single nucleotide variants (SNV) of the genes of oxytocin (OXT, OXTR) and vasopressin (AVP, AVPR1A, AVPR1B) systems, which are associated with the regulation of social and emotional behavior in distinct populations. The analysis was performed using original WGS (whole genome sequencing) data on Eastern Slavs (SlEast), as well as publicly available data from the 1000 Genomes Project on GBR, FIN, IBR, PUR, BEB, CHB, and ACB populations (the latter were taken as reference). To identify selection signatures, we rated the integrated haplotype scores (iHS), the numbers of segregating sites by length (nSl), and the integrated haplotype homozygosity pooled (iHH12) measures; the fixation index Fst was implemented to assess genetic differentiation between populations. We revealed that the strongest genetic differentiation of populations was found with respect to the AVPR1B gene, with the greatest differentiation observed in GRB (Fst = 0.316) and CHB (Fst = 0.325) in comparison to ACB. Also, high Fst values were found for SNVs of the AVPR1B gene rs28499431, rs33940624, rs28477649, rs3883899, and rs28452187 in most of the populations. Selection signatures have also been identified in the AVP, AVPR1A, OXT, and OXTR genes. Our analysis shows that the OXT, OXTR, AVP, AVPR1A, and AVPR1B genes were subject to positive selection in a population-specific process, which was likely contributing to the diversity of adaptive emotional response types and social function realizations.

Socially Mediated Shift in Neural Circuits Activation Regulated by Synergistic Neuromodulatory Signaling.

Animals exhibit context-dependent behavioral decisions that are mediated by specific motor circuits. In social species these decisions are often influenced by social status. Although social status-dependent neural plasticity of motor circuits has been investigated in vertebrates, little is known of how cellular plasticity translates into differences in motor activity. Here, we used zebrafish (Danio rerio) as a model organism to examine how social dominance influences the activation of swimming and the Mauthner-mediated startle escape behaviors. We show that the status-dependent shift in behavior patterns whereby dominants increase swimming and reduce sensitivity of startle escape while subordinates reduce their swimming and increase startle sensitivity is regulated by the synergistic interactions of dopaminergic, glycinergic, and GABAergic inputs to shift the balance of activation of the underlying motor circuits. This shift is driven by socially induced differences in expression of dopaminergic receptor type 1b (Drd1b) on glycinergic neurons and dopamine (DA) reuptake transporter (DAT). Second, we show that GABAergic input onto glycinergic neurons is strengthened in subordinates compared with dominants. Complementary neurocomputational modeling of the empirical results show that drd1b functions as molecular regulator to facilitate the shift between excitatory and inhibitory pathways. The results illustrate how reconfiguration in network dynamics serves as an adaptive strategy to cope with changes in social environment and are likely conserved and applicable to other social species.

Addressing disruptive behaviors within naturalistic developmental behavioral interventions: Clinical decision-making, intervention outcomes, and implications for practice.

Naturalistic developmental behavioral interventions are a common and well-researched type of intervention for young autistic children that focus on supporting social communication. These interventions often do not include formal guidelines on how to address disruptive behaviors, even though they are common among autistic children. This study measured how often clinicians delivering a specific naturalistic developmental behavioral intervention, Project ImPACT, adapted how they delivered the program to address disruptive behavior, and how these adaptations related to children's social communication outcomes at the end of their participation in the intervention. We also spoke with clinicians about how they address disruptive behavior and emotion regulation during their sessions. In this study, clinicians adapted Project ImPACT to address disruptive behaviors in about one-third of all sessions. These adaptations did not affect children's social communication outcomes. Clinicians discussed how they felt social communication, disruptive behavior, and emotion regulation are linked to one another and that they often try to integrate intervention strategies to address each of these areas. However, they note that a clinicians' approach to addressing disruptive behavior might vary depending on their level of training and experience. These results indicate several future directions for supporting clinicians in addressing behavior and regulation effectively within these types of interventions.

Brain and circulating steroids in an electric fish: Relevance for non-breeding aggression.

Steroids play a crucial role in modulating brain and behavior. While traditionally it is thought that the brain is a target of sex steroids produced in endocrine glands (e.g. gonads), the brain itself produces steroids, known as neurosteroids. Neurosteroids can be produced in regions involved in the regulation of social behaviors and may act locally to regulate social behaviors, such as reproduction and aggression. Our model species, the weakly electric fish Gymnotus omarorum, displays non-breeding aggression in both sexes. This is a valuable natural behavior to understand neuroendocrine mechanisms that differ from those underlying breeding aggression. In the non-breeding season, circulating sex steroid levels are low, which facilitates the study of neurosteroids. Here, for the first time in a teleost fish, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify a panel of 8 steroids in both plasma and brain to characterize steroid profiles in wild non-breeding adult males and females. We show that: 1) systemic steroid levels in the non-breeding season are similar in both sexes, although only males have detectable circulating 11-ketotestosterone, 2) brain steroid levels are sexually dimorphic, as females display higher levels of androstenedione, testosterone and estrone, and only males had detectable 11-ketotestosterone, 3) systemic androgens such as androstenedione and testosterone in the non-breeding season are potential precursors for neuroestrogen synthesis, and 4) estrogens, which play a key role in non-breeding aggression, are detectable in the brain (but not the plasma) in both sexes. These data are consistent with previous studies of G. omarorum that show non-breeding aggression is dependent on estrogen signaling, as has also been shown in bird and mammal models. Overall, our results provide a foundation for understanding the role of neurosteroids, the interplay between central and peripheral steroids and potential sex differences in the regulation of social behaviors.

Роль установок на авторитаризм и социальное доверие в проявлениях гражданской и онлайн-активности

&lt;p style="text-align: justify;"&gt;Attitudes towards authoritarianism, social dominance, social competition and social trust are important regulators of social behavior. Therefore, correlating attitudes with commitment to various forms of activity is an important step towards understanding and specifying their role in behavior. The purpose of the study is to identify the role of attitudes towards authoritarianism and social trust in the manifestations of civic and on-line activity of Russian youth. Participants. The study involved young people aged 17-35 years (average age M=21.8; SD=6.2) in the number of 442 people (men - 33.5%, women - 66.5%). The sample is representative of the provincial regions of central Russia of economically different strata. Methods. The forms of social activity were measured using direct scaling, the types of activity were determined based on factor analysis. To determine the settings, the J. Dakkit&amp;rsquo;s scale was used in D.S. Grigoriev's adaptation. Indicators of trust are determined using the Scale of interpersonal trust of J. Rotter in the adaptation of I.Y. Leonova, I.N. Leonova. Correlations have been established between indicators of right-wing authoritarianism, institutional trust with commitment to civic (positive) and Internet network (negative) activity; belief in a competitive world &amp;mdash; with a commitment to civic (positive) and protest (negative) activity. As a result of structural modeling, the hypothesis about the direct effect (directed connection) of right-wing authoritarianism and belief in a competitive world on commitment to civic and Internet network activity is confirmed. The role of different attitudes in adherence to certain types of activity varies. Their isolated contribution to activity can reach 16-19%, together with age, religiosity and trust - 19-26% of variations. Trust plays the role of a mediator of a direct connection between attitudes and activity, and at the same time, right-wing authoritarianism also plays the role of a mediator of a direct causal connection between age, subjective religiosity and civic and Internet network activity.&lt;/p&gt;

Imaging Analyses of Oxytocin: Visualization of Oxytocin and Its Implications

Oxytocin, long known for its peripheral action, is a strong regulator of social behaviors through its actions in the brain. Despite such recognition, its sites of actions and dynamics within the brain tissues remain poorly understood owing to the lack of appropriate tools for its visualization and characterization. Conventional fluorescence-tagging is not applicable for small-sized bioactive molecules like oxytocin. Herein, our attempt to overcome this limitation is introduced using our novel strategy, alkyne-tagging. Small-sized alkynes would facilitate specific tagging and subsequent visualization of oxytocin within the body, which would bring forth new insights into the modes of oxytocin's action in the brain.

Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory.

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.

Post-weaning social isolation in male mice leads to abnormal aggression and disrupted network organization in the prefrontal cortex: Contribution of parvalbumin interneurons with or without perineuronal nets

Adverse social experiences during childhood increase the risk of developing aggression-related psychopathologies. The prefrontal cortex (PFC) is a key regulator of social behavior, where experience-dependent network development is tied to the maturation of parvalbumin-positive (PV+) interneurons. Maltreatment in childhood could impact PFC development and lead to disturbances in social behavior during later life. However, our knowledge regarding the impact of early-life social stress on PFC operation and PV+ cell function is still scarce. Here, we used post-weaning social isolation (PWSI) to model early-life social neglect in mice and to study the associated neuronal changes in the PFC, additionally distinguishing between the two main subpopulations of PV+ interneurons, i.e. those without or those enwrapped by perineuronal nets (PNN). For the first time to such detailed extent in mice, we show that PWSI induced disturbances in social behavior, including abnormal aggression, excessive vigilance and fragmented behavioral organization. PWSI mice showed altered resting-state and fighting-induced co-activation patterns between orbitofrontal and medial PFC (mPFC) subregions, with a particularly highly elevated activity in the mPFC. Surprisingly, aggressive interaction was associated with a higher recruitment of mPFC PV+ neurons that were surrounded by PNN in PWSI mice that seemed to mediate the emergence of social deficits. PWSI did not affect the number of PV+ neurons and PNN density, but enhanced PV and PNN intensity as well as cortical and subcortical glutamatergic drive onto mPFC PV+ neurons. Our results suggest that the increased excitatory input of PV+ cells could emerge as a compensatory mechanism for the PV+ neuron-mediated impaired inhibition of mPFC layer 5 pyramidal neurons, since we found lower numbers of GABAergic PV+ puncta on the perisomatic region of these cells. In conclusion, PWSI leads to altered PV-PNN activity and impaired excitatory/inhibitory balance in the mPFC, which possibly contributes to social behavioral disruptions seen in PWSI mice. Our data advances our understanding on how early-life social stress can impact the maturing PFC and lead to the development of social abnormalities in adulthood.