Developmental Psychobiology

Preterm birth is associated with alterations in early caregiver-infant regulation, with potential consequences for socio-emotional and physiological development. However, the mechanisms through which early interactional experience shapes these processes remain unclear. Here, we tested whether a structured dyadic intervention could modify co-regulatory dynamics across physiological, behavioral, and relational levels. Fifty-four 7-month-old preterm infants and their parents were assigned to either a shared book reading intervention (n = 22) or an active control condition based on a shared building activity (n = 32) and compared with 39 full-term infants. The intervention consisted of an 8-week program of shared book reading, designed to structure parent-infant interaction. Physiological synchrony was assessed at the dyadic level, alongside infants autonomic regulation and cardiovascular signal complexity. Behavioral engagement and parental attachment representations were also evaluated. Results showed that mother-infant physiological synchrony emerged selectively within the interactional context trained by the intervention and only in the intervention group. This context-specific synchrony was accompanied by modulation of vagal activity and increased cardiovascular complexity in preterm infants, consistent with enhanced flexibility of autonomic control. At the behavioral and relational levels, intervention infants showed increased initiating joint attention, while parents reported higher secure attachment. These findings support a model of experience-dependent early synchrony, in which repeated dyadic interaction through shared book reading shapes the coupling between interpersonal coordination and individual physiological regulation. By linking synchrony, autonomic flexibility, and social engagement, this study identifies a mechanism through which early caregiving experience can organize developmental trajectories following prematurity.

Although female rats are typically less aggressive than male rats, lactating females will vigorously defend their nests and pups against an intruder. Much attention has been directed at the consequences of this aggression on the intruder and less on the consequences for the mother and her subsequent interactions with her pups. Here, we exposed resident Sprague-Dawley dams to the resident-intruder paradigm twice daily for five consecutive days, beginning when the dam's (RES) pups were 7 days old, to assess social stress effects on maternal behavior and neurobiology. Controls were dams that had time-matched (TMC) separation from their pups but were not exposed to intruders, and naive moms which were never separated nor exposed to an intruder (CTL). We assessed the dam's subsequent behavior and interactions with her pups on Day 1 and Day 5, and Fos expression after Day 5 in select regions of the prefrontal cortex, amygdala, hypothalamus and periaqueductal gray of the midbrain. In separate cohorts, after pups were weaned, the dams underwent restraint stress and plasma corticosterone assayed. PCA analysis of the dam's behaviors identified three components: normal self-focused behaviors; nurturing behaviors and rough non-nurturing behaviors. Relative to CTL, RES dams exhibited more disrupted behaviors towards their pups, including, rough transport, stepping on pups, and flinging/tossing pups around the cage. In contrast, TMC Dams showed some, but fewer changes relative to CTL, suggesting that separation from pups alone does not account for all disrupted behavior in RES dams. The bulk of these behavioral effects occurred in the first 5-10 min after reunion with the pups and were seen on both the first and fifth day of testing. Of the brain regions examined, the prefrontal cortex was activated by both the defeat/intruder stress (RES) and separation stress (TMC), whereas the dorsal PAG was activated specifically by the defeat/intruder stress. The medial and basolateral amygdala exhibited differential neuronal activity between the RES defeat/intruder-exposed dams and the other two groups. The RES moms exhibited an insufficient adrenocortical response to acute restraint stress. The results suggest that amygdala-dPAG activity is important for dissociating disrupted maternal care in RES (due to defense of the nest against an intruder) from simple pup separation, both of which activate the mPFC. The experience of repeatedly defending the nest may induce subsequent disruptions in HPA responses. The amygdala-dPAG pathway may regulate aspects of stress and emotional regulation exhibited by mothers who defend their offspring against intruders.

The hypothalamus plays a central role in integrating physiological stressors to maintain homeostasis, yet how fetal neurodevelopment in the hypothalamus is shaped by intrauterine maternal stress exposure remains understudied. This is especially true in the context of sex-divergent mechanisms underlying neurodevelopmental disorders (NDDs), which are increasingly being linked to perturbation of the intrauterine environment. Herein, we utilize a mouse model of prenatal maternal cold stress exposure to study the impacts on neural stem and progenitor cell (NSPC) developmental programs in the fetal hypothalamus. Pregnant mice were exposed to cold stress from embryonic day 11.5 (E11.5) to E15.5 and fetal hypothalamic NSPCs from both male and female embryos were analyzed. Maternal stress induced sex-specific effects in the fetal hypothalamus, increasing TUJ1+ neuron number in males, while enhancing neuronal dendritic arborization in females. To define underlying molecular changes, we performed single-cell RNA sequencing of hypothalamic NSPCs. Interestingly, we identified distinct baseline transcriptional profiles between male and female NSPCs and found that maternal stress shifts female NSPCs toward a more male-like transcriptional state. In females, maternal stress upregulated pathways related to GABAergic differentiation and neuronal projection morphogenesis, with these alterations maintained across more differentiated neuronal populations. Ligand-receptor analysis further indicated that maternal stress alters cell-cell communication within NSPCs, predominantly in females. Together, these findings demonstrate that prenatal maternal stress drives sex-specific alterations in hypothalamic NSPC developmental programs and suggest that disrupted intercellular signaling may contribute to underlying sex differences in social behaviors previously reported for this model (Rosin et al., 2021). SIGNIFICANCE STATEMENTPrenatal stress is a known risk factor for NDDs, but how it shapes early brain development in a sex-specific manner remains understudied. Here, we examined how maternal stress influences NSPCs in the hypothalamus, a brain region critical for regulating the stress response and homeostasis. Using mice as a model system, we found that maternal stress alters how fetal NSPCs develop into neurons in a sex-specific manner. Molecular analyses suggest that maternal stress shifts female NSPCs to become more male-like and alters cell-cell communication. This work advances our understanding of how prenatal maternal stress drives sex differences in neurodevelopmental programming and may help to begin to explain sex-biased vulnerabilities to NDDs.

Time perception difficulties are frequently reported in Autism Spectrum Disorder, yet empirical findings remain inconsistent. A key methodological limitation is the failure to separate perceptual sensitivity from decision-making strategies. We applied Signal Detection Theory (SDT) to a subsecond duration discrimination task (100 and 500 ms) in 65 non-clinical adults varying in autistic traits, assessed via the Autism-Spectrum Quotient (AQ) and a Principal Component Analysis (PCA) of its subscales. Autistic traits did not predict reduced perceptual sensitivity (d'): temporal discrimination remained intact across the full autism-trait continuum, with Bayesian analyses providing converging evidence against a perceptual deficit. Instead, a PCA-derived cognitive component -- combining heightened Attention to Detail with reduced Imagination -- was systematically associated with a shift in decision bias (c). Individuals with this profile showed a graded attenuation of standard-based anchoring, with ordinal position progressively filling the gap. This shift operated consistently across both temporal scales, as confirmed by trial-level generalized linear mixed modelling, and reflects a quantitative redistribution of anchoring weight rather than a categorical switch in strategy. These findings reframe temporal "rigidity" in ASD not as a perceptual deficit, but as a suboptimal yet internally consistent decision-making style favouring within-trial information over accumulated representational knowledge. Lay AbstractMany autistic people report difficulties with time in daily life, but scientists have long disagreed on whether this reflects a genuine perceptual problem. This study found that autistic traits do not impair the basic ability to judge duration. Instead, people with more autistic traits tend to rely on which event came first, rather than accumulating experience across trials to refine their judgments -- a less effective but internally consistent strategy.

BackgroundMaternal oxycodone (oxy) exposure can disrupt placental function and fetal neurodevelopment, but the molecular mechanisms remain unclear. We investigated whether prenatal oxy exposure activates inflammation and stress response pathways in the placenta and fetal brain, and if maternal melatonin supplementation attenuates these effects. MethodsFemale Sprague-Dawley rats received either saline or oxy via oral gavage for 15 days before mating (10-15mg/kg/day dose escalation) and throughout pregnancy (15mg/kg/day). From gestational day (GD) 12.5, half of the dams received melatonin (10mg/kg/day). On GD 19.5, placental and fetal brain tissues were collected. Changes in expression of markers of oxidative stress, antioxidant defense signaling, inflammation, ER stress, and apoptosis were assessed by western blotting. Data were analyzed by two-way ANOVA with Tukeys post hoc test. ResultsNeither oxy exposure nor melatonin treatment increased markers of oxidative stress or antioxidant defenses in the placenta and fetal brain. Oxy exposure increased placental IL-1{beta} expression but did not alter expression of the other inflammatory markers examined. Oxy increased phosphorylation of eIF2 and increased the phospho-eIF2:eIF2 ratio in the placentas of male fetuses, and fetal brains of both sexes. CHOP expression was increased in the placentas and brains of female, but not male fetuses after oxy exposure. Oxy exposure increased levels of cleaved caspase-3 and cleaved caspase-9 in the fetal brain, but not the placenta; melatonin treatment attenuated the oxy-induced increase in cleaved caspase-9, but not cleaved caspase-3. ConclusionPrenatal oxy exposure induced a modest inflammatory response in the placenta and activated the integrated stress response and intrinsic apoptotic signaling in the fetal brain. Maternal melatonin supplementation partially mitigated the oxy-induced upregulation of caspase-9 but did not prevent stress signaling in either tissue. These findings demonstrate the presence of sex-specific placental and fetal brain responses to prenatal oxy exposure but suggest that melatonin may not provide complete protection against oxy-induced neurodevelopmental impairment.

BackgroundPrenatal oxycodone (oxy) exposure has been associated with adverse pregnancy and fetal developmental outcomes. In this study, we assessed whether chronic prenatal oxy exposure impairs placental and fetal growth in rats and if maternal melatonin supplementation would mitigate these effects. MethodsFemale Sprague-Dawley rats received either saline or oxy via oral gavage for 15 days before mating (10-15mg/kg dose escalation) and throughout pregnancy (15mg/kg). From gestational day (GD) 12.5, half of the dams received melatonin (10mg/kg). On GD19.5, maternal and fetal blood, and maternal, placental and fetal tissues were harvested. Placental histomorphometry was assessed and immunohistochemistry for pan-cytokeratin, PCNA, CD34, -SMA, and TUNEL analysis were performed. Maternal and fetal plasma cytokines, angiogenic factors, and pregnancy hormones were measured by ELISA. Anthropometric data were analyzed using general linear mixed models and other outcomes were analyzed using univariate general linear models. ResultsOxy induced fetal growth restriction as evidenced by reduced placental weight, fetal weight, fetal-to-placental weight ratio, crown-rump length, and fetal liver weight. Melatonin also independently reduced some parameters of fetal growth but when administered with oxy it partially improved fetal outcomes including the head-to-abdominal diameter ratio. Oxy exposure increased placental labyrinth zone area, the percentage of CD34-positive cells, and maternal plasma IL-1{beta} and IL-10 concentrations and reduced the percentage of pan-cytokeratin positive cells, while both oxy and melatonin reduced maternal plasma chorionic gonadotropin levels. ConclusionPrenatal oxy exposure disrupts placental structure, labyrinth anatomy, and induces maternal systemic inflammation, associated with impaired fetal growth. The protective effects of melatonin are partial but indicate a potential brain sparing effect.

RationaleAdolescence is a period of heightened vulnerability to nicotine reinforcement. While zebrafish are a valuable model for investigating drug reward, standard conditioned place preference (CPP) assays typically test subjects in isolation. In this highly social species, solitary testing may act as an environmental stressor that confounds behavioral readouts. ObjectivesThis study examined how social context during testing (isolated vs. grouped) affects experimental attrition, behavioral stability, and nicotine CPP expression in late juvenile zebrafish. MethodsZebrafish housed in groups of four were tested either individually (isolated) or in their housing groups (grouped) during daily 20-minute sessions. Following baseline preference assessments, subjects underwent six days of conditioning pairing their initially non-preferred compartment with fish water or nicotine (0.5, 1.6, or 5.0 {micro}mol/L). Place preference, locomotion, and thigmotaxis were assessed on a drug-free test day. ResultsIsolated testing reduced distance traveled, decreased swimming speed, and increased time spent near tank walls, indicating heightened anxiety-like behavior. Experimental attrition was significantly higher in isolated (38.9%) than grouped (2.5%) subjects. Grouped subjects developed significant place preference at 1.6 and 5.0 {micro} mol/L nicotine, whereas preference was not detectable in isolated subjects. ConclusionsSolitary testing acts as a stressor that increases experimental attrition and masks place preference. Conversely, testing in the presence of conspecifics stabilizes behavior and facilitates the detection of nicotine reward in late juvenile zebrafish.

Social behavior is a fundamental phenotype across vertebrates. Zebrafish (Danio rerio) have emerged as a valuable translational model for investigating the neurobiological mechanisms underlying sociability, particularly due to their robust shoaling behavior and experimental tractability. However, the literature presents issues of reproducibility and inconsistent findings regarding the modulation of social preference and shoal cohesion in adult zebrafish. We conducted a systematic review and meta-analysis to synthesize studies evaluating the effects of pharmacological interventions that modulate the central nervous system and stress-related interventions on social behavior in adult zebrafish and, when available, anxiety-like behavior. The literature search was performed in three databases (Embase, PubMed, and Web of Science), followed by a two-step screening process based on inclusion/exclusion criteria. The included studies underwent extraction of qualitative and quantitative data, as well as risk of bias assessment. Interventions from the included studies (n = 108) were categorized according to their nature, mechanism of action, and/or therapeutic purpose, resulting in seven, four, and five meta-analyses for social preference, shoal cohesion, and anxiety-related tests, respectively. Ethanol, NMDA antagonists, pro-dopaminergic agents, and stress-related interventions decreased social preference, while stress-related interventions increased shoal cohesion. The fact that stress produced opposite effects suggests that these paradigms measure distinct sociability constructs, or perhaps are differentially modulated by confounding factors, like anxiety for example. The studies presented high heterogeneity, with prediction intervals compatible with effects in both directions, as well as methodological limitations and deficiencies in data reporting, as evidenced by the risk of bias assessment. These findings emphasize the need for well-designed new studies to validate the findings and expand the evidence on interventions that currently lack sufficient studies for quantitative synthesis.

Stress during critical developmental periods causes lasting neurobiological alterations. Rodent models like neonatal maternal separation (NMS) induce cognitive alterations, particularly spatial memory deficits. Oxytocin (OT) system has been suggested to underlie these consequences, as it is critical for neurodevelopment. This neuropeptide also promotes maternal nurturing, prevents neuroinflammation and displays anxiolytic properties. This study hypothesized that early postnatal OT administration could prevent NMS-induced memory alterations in adult rats. Sprague-Dawley rat pups (both sexes, n=8-12/group) underwent NMS with concomitant intraperitoneal OT injections. At adulthood, novel object recognition and object location tasks were performed. Further investigation was conducted through ex vivo electrophysiological recordings of functional plasticity at Schaffer collateral-CA1 synapses (male, n=7-12/group), alongside RT-qPCR of synaptic, GABAergic, neuro-inflammatory, and oxytocin receptor markers in dorsal CA1 (male, n=4-6/group). NMS induced male-specific spatial memory impairment without affecting recognition memory. Early OT completely prevented spatial memory deficits in NMS males. Electrophysiological recordings revealed that NMS suppressed CA1 long-term potentiation (LTP), and neonatal OT restored it. NMS induced transcript overexpression of neuro-inflammatory markers, GABAergic markers, and synaptic proteins in dorsal CA1. OT treatment normalized or reduced these mRNA expressions, consistent with restoration of CA1 synaptic function. Early postnatal OT prevents NMS-induced spatial memory deficits and hippocampal LTP impairments in male rats, which is associated with normalized or reduced neuro-inflammatory and GABAergic transcript expressions. These findings establish exogenous oxytocin administration during a critical neonatal window as sufficient to prevent male-specific hippocampal dysfunction and cognitive deficits induced by early-life stress, identifying the oxytocinergic system as a promising target for early neuroprotective interventions.

IntroductionAdolescence is a sensitive developmental period during which chronic stress can induce lasting adaptations in corticolimbic circuits involved in stress regulation, cognition, and emotional behavior. We examined the long-term behavioral, endocrine, and molecular consequences of adolescent chronic variable stress (CVS) in male and female rats, focusing on the infralimbic cortex (IL) and basolateral amygdala (BLA) MethodsSprague Dawley rats of both sexes were exposed to CVS during late adolescence and evaluated in adulthood after an extensive recovery period. Behavioral testing included cued fear conditioning and extinction recall, delayed spatial win-shift, novel object recognition, Morris water maze, three-chamber social behavior, and passive avoidance. HPA-axis reactivity to acute restraint was assessed. Targeted qPCR was used to measure stress-related gene expression in the IL and BLA immediately after stress or after a 5-week recovery period ResultsAdolescent CVS did not cause generalized cognitive impairment, but instead produced selective, sex-specific effects. Females had reduced HPA responses to acute stress and mild deficits in delayed spatial win-shift performance, together with long-term IL changes in genes related to adrenergic signaling, plasticity, and GABA clearance. Males showed enhanced Morris water maze probe retention, weaker novel object discrimination, altered passive avoidance with marked inter-individual variability, and enhanced social preference. At the molecular level, males exhibited long-term upregulation of Fkbp5 in IL and downregulation of PACAP, 1D adrenergic receptor, and proenkephalin in BLA, whereas females showed delayed PACAP upregulation in BLA DiscussionAdolescent CVS induces persistent, sex- and region-specific recalibration of corticolimbic function, supporting distinct patterns of vulnerability and resilience, rather than uniform stress pathology.

Atypical processing of emotional faces has been proposed as a characteristic of Autism Spectrum Disorder (ASD), but functional neuroimaging research has yielded inconsistent findings. Prior work is limited in generalizability due to methodological heterogeneity, imbalanced or small sample sizes, and underrepresentation of females. The present study examined functional brain activation during the Hariri Emotional Face-Matching Task (EFMT) in a large, sex-balanced sample of both typically developing and ASD participants (n=295, 8-18 years old) from the multi-site Autism Center of Excellence GENDAAR project. Using an ROI-driven approach, we targeted the right FFA, right OFA, right pSTS, and bilateral amygdala, we investigated whether ASD diagnosis was associated with atypical regional activation when viewing emotional faces, and if these differences were generalizable across sexes. Results revealed a group-by-sex interaction in the right FFA, driven by divergence of ASD males from the ASD female and typically developing participants. Generally, ASD females did not diverge greatly from typically developing populations. These findings suggest that atypical face processing is present, but meaningfully modulated by sex, underscoring the importance of sex-balanced, well-powered developmental samples in autism.

Standard rat housing may impede species-typical behaviors and impact rat welfare and research outcomes. This research investigated the effects of housing on behavioral and physiological outcomes of rats through the use of modified large animal cages for housing, and was conducted in two studies. Study A: 70 Sprague Dawley (SD) rats (34 males, 36 females; 5 wk old) were randomly assigned to standard polycarbonate shoebox cages (C: 733.9cm2) or modified stainless steel primate cages (T: 10,416cm2) for 18 days. In Study B: 48 SD rats (24 males, 24 females; 7.5 wk old) were held in T housing for 90 days to assess long term impacts. All rats received gentle handling for 15s 3x/week. Rats were assessed for body weight, anxiety-like behavior in an elevated plus maze, response during a voluntary human approach test, and overall home cage behavior, posture, and space usage. Data were analyzed using generalized linear mixed models, with sex and treatment as fixed effects, and cage as the random effect. The results of study A suggest that the modified large animal cages (T) had positive impacts on rat behavior and welfare. T rats were less anxious (P=0.038) and more active (P<0.0001) and explorative (P=0.0003) compared to C rats. In both groups, activity levels declined towards the end of the 18-day study period (P<0.0001). For study B, similar patterns were observed, with rats becoming more inactive (P<0.0001) over 90 days. However, rats spent significant time on elevated shelves in T housing, which increased throughout the study (P<0.0001), suggesting continued use of the resources the housing provided. In both studies, there were no differences in latency to approach humans (P>0.05), but T rats spent less time in contact with human handlers, suggesting differences in motivation to interact with humans that should be explored further.

Emerging evidence indicates that the maternal in utero environment has enduring effects on offspring neurodevelopment. The obesity epidemic in the United States affects nearly one-third of women before pregnancy, potentially predisposing offspring to harmful developmental conditions. Glucose, the primary energy source for the brain, is highly regulated by facilitative diffusion glucose transporters (GLUTs). However, our understanding of how maternal obesity influences perinatal cerebral glucose metabolism remains limited. We hypothesized that maternal obesity is associated with altered expression of key GLUTs and dysregulated energy-sensing mechanisms in the fetal brain. Female C57BL/6J mice were randomly assigned to either a control diet (CON) or an obesogenic diet (DIO) (60% kcal from fat, 17.5% kcal from sucrose) for 10 weeks, time-mated with control males, and fed their respective diets throughout gestation. At 18.5 days post coitum, fetal brain tissue was collected for protein analysis. DIO diet did not affect litter size, offspring body weight, or brain weight when compared to CON. Whole brain GLUT1 expression was elevated only in female DIO offspring, while GLUT3 and GLUT4 expression was increased in all DIO offspring without modification by sex. However, maternal diet was not associated with differences in the activation of energy regulatory pathways adenosine monophosphate-activated protein kinase (AMPK) or the nutrient-sensing pathway mechanistic target of rapamycin (mTOR) in the fetal brain. These findings suggest that maternal obesogenic diet alters glucose transporter expression in the fetal brain, indicating a potential disruption in cerebral glucose metabolism during critical periods of perinatal development.

Lack of social interaction results in various behavioral abnormalities in rodents, including increased anxiety levels, altered sociability, and impaired cognitive ability. Epigenetic factors regulate gene expression, however, how they contribute to juvenile social isolation (jSI)-induced behavioral alterations remains largely unknown. Here, we focused on the nucleus accumbens (NAc), a critical brain region of the reward system that regulates motivation-related behaviors. We first performed RNA-seq on neuronal nuclei and found alterations in genes related to neuronal function, as well as in transcriptional and epigenetic regulation. Protein-protein interaction (PPI) analysis of differentially expressed genes (DEGs) showed that top key nodes among down-regulated genes include membrane receptors (Ntrk2, Grin3a, and Grik1) and an apoptosis regulator (Bcl2). To further investigate whether jSI-induced gene expression alterations are mediated by histone modifications, we next performed CUT&Tag for four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3), and the results implied that epigenetic alterations may also play a role in neuronal function as well as transcriptional regulation. Reanalysis of previously published RNA-seq data on the manipulation of histone modification-associated factors (including Kdm6b, Brd4, and Setd1a) suggested that these enzymes were probably involved in jSI-induced gene expression alterations. Taken together, our comprehensive analysis implies the involvement of histone modification regulation in jSI-related alterations of gene expression in NAc.

Background: Childhood trauma exposure (TE) may heighten negative emotional responses, overwhelm cognitive control, and increase risk for anxiety disorders. Cognitive control is facilitated by glutamatergic (Glu) excitatory neurotransmission within the dorsal anterior cingulate cortex (dACC). Dynamic changes in dACC Glu levels were investigated using 1H functional magnetic resonance spectroscopy (1H fMRS) to assess the impact of negative emotional processing on neural mechanisms supporting cognitive control in TE-youth. Methods: Fifty adolescents were categorized into two TE-Groups: Higher (Mtrauma=6{+/-}1events) and Lower (Mtrauma=3{+/-}1events). 1H fMRS from the dACC was acquired during an inhibitory motor control task requiring tapping responses to stimuli under two Response Modes, NonSelective (100% response) and Selective (80% response, 20% inhibition), executed with two Stimuli Conditions, Squares (no emotion) and Faces (emotion). Glu modulation (relative to basal levels) was tested across TE-Group, Stimuli Condition, and their interaction. Within each Stimuli Condition, Glu modulation was tested across Response Modes by TE-Group. Results: We observed a 2-way interaction of TE-Group x Stimuli Condition ({chi}2=4.66, p=0.031). Post-hoc tests revealed significantly lower Glu modulation in Higher TE vs Lower TE (p=.023) during Faces but not Squares. This Glu modulation did not differ across Response Modes. Within the Higher TE-Group, Glu was significantly reduced during Faces compared to Squares (p<.001). Basal dACC Glu levels did not differ between groups. Conclusions: TE-Group differences in adolescent dACC Glu modulation were observed during cognitive control performed with emotional, but not non-emotional, stimuli, highlighting the value of 1H fMRS for detecting trauma-related differences in task-related excitatory neurochemical dynamics.

Early-life stress elevates the risk of developing neuropsychiatric disorders. However, the mechanism underlying this vulnerability, and how they contribute to sex differences in these disorders, remain to be understood. Here, we use multivariate brain-based predictive models to examine how the number, positive or negative appraisal, and impact of adolescent stressful life events reported either by the youth or their caregivers are reflected in neuroanatomy (cortical thickness, surface area, cortical and subcortical gray matter volume, and T1 intensity measures). We used data from the Adolescent Brain Cognitive Development (ABCD) study at 2-year (N = 6,301, age 11-12), 4-year (N = 5,000, age 13-14) and 6-year (N = 3,226, age 15-16) follow-up time points to examine the sex-independent and sex-specific neural correlates of stressful life events. Our analyses showed mostly non-significant associations between stressful life events and neuroanatomy. However, we did find that the number of positively appraised stressful life events reported by the caregivers at the 4-year follow-up was significantly associated with cortical thickness, independent of sex, and with surface area in females only. Across three developmental timepoints, seven neuroanatomical measures, two reporting perspectives, and both sex-independent and sex-specific analyses, we show that the number, appraisal, and impact of stressful life events are largely not reflected in adolescent neuroanatomy.

The types of faces that infants see impact their developing ability to engage with and individuate people from familiar and unfamiliar social groups, a phenomenon known as perceptual narrowing. However, the neural mechanisms that underlie infants processing of different faces as a function of experience remain poorly understood. To address this gap, the present study analyzes electroencephalography data collected while 3-month-olds (N=24), 6-month-olds (N=26), and 9-month-olds (N=18) viewed female and male faces of a familiar or unfamiliar social group. Infants neural responses to faces differed by group familiarity from 3 months of age, with increased responses to the more familiar face types in early components (P1, N290), and to the more unfamiliar face types in later components (P400, Nc). Face sex and group familiarity interacted to shape N290 and P400 amplitudes at 3- and 9-months. Specifically, N290 amplitudes were greater in response to female faces of a familiar group at 3 months, and to male faces of a familiar group at 9 months. In contrast, P400 amplitudes were greater in response to male faces of an unfamiliar group at 3 months old, and greatest in response to both female faces of a familiar group and to male faces of an unfamiliar group at 9 months. Source reconstruction of the Nc revealed greater reconstructed current density in response to faces of an unfamiliar social group across all ages. These findings contribute to a growing body of knowledge examining how perceptual experiences shape infants understanding of their social world.

Disruptions in excitatory-inhibitory (E/I) balance during neurodevelopment have been implicated in a range of psychiatric conditions, yet the neurochemical alterations associated to early-life insults and their potential contribution to E/I imbalance remain poorly understood. Using a "two-hit" rat model combining maternal immune activation (MIA; lipopolysaccharide -LPS- on gestational days 15-16) and peripubertal unpredictable stress (PUS; postnatal days 28-38), we examined the long-term effects of these insults, alone and in combination, on the adult dorsal hippocampus. Assessments included gene and/or protein expression of glutamatergic and GABAergic markers, endocannabinoid system enzymes, neuromodulatory amino acid level and prepulse inhibition (PPI) of the acoustic startle response. MIA increased GluN1 protein expression, while PUS reduced the Grin2a/Grin2b mRNA ratio, indicating incomplete NMDA receptor subunit maturation. GABA levels and GABA-A{gamma}2 expression were unchanged, suggesting deficient inhibitory compensation in the face of heightened excitatory tone. PUS increased Mgll gene expression, whereas a trend towards reduced Dagla expression was observed exclusively in non-stressed LPS-exposed animals, suggesting that MIA may suppress 2-AG synthesis only in the absence of subsequent stress. MIA and PUS displayed interactive effects on taurine levels, with elevation observed only in the double-hit condition; glycine was elevated by MIA independently of PUS. These findings support a model in which MIA and PUS converge on hippocampal E/I balance through complementary adaptations -- excitatory upregulation, incomplete synaptic maturation, and reduced endocannabinoid tone -- inadequately counterbalanced by inhibitory systems. Taurine and glycine emerge as potential markers of homeostatic compensation in response to early neurochemical dysregulation.

BackgroundSocial behaviour is essential for the survival of most mammalian species and is shaped by sex-dependent genetic and endocrine factors. However, how sex influences brain-wide neural dynamics during social interactions remains poorly understood. MethodsHere, we investigated sex differences in neural activity across a distributed amygdalo-striatal network in freely behaving mice. Using chronically implanted electrode arrays, we simultaneously recorded extracellular activity from multiple amygdalo-striatal regions while mice performed four social discrimination tasks. Neural signals were analysed alongside video-based behavioural tracking and head acceleration measurements. ResultsWe identified significant sex differences in neural activity that emerged even before social interaction, suggesting distinct anticipatory network states. During social interaction, sex differences were distributed across brain regions and electrophysiological features, but were most consistently expressed in the basolateral amygdala (BLA). Notably, BLA activity exhibited pronounced sex-specific, context- and time-dependent dynamics, particularly during the initial phase of social interaction. These neural differences were associated with variations in behavioural responses and movement dynamics. ConclusionsTogether, our findings reveal that sex shapes both baseline and interaction-driven neural activity across the social brain network, and highlight the BLA as a key node underlying sex-specific dynamics of social behaviour. Plain English summarySocial behaviour is essential for survival and differs between males and females in many species, including humans and mice. These differences are influenced by biological factors such as genes and hormones, but how they are reflected in brain activity during social interactions is still not fully understood. In this study, we examined how brain activity differs between male and female mice during social behaviour. We recorded neural activity simultaneously from several brain regions involved in social and emotional processing while mice performed four different social interaction tasks. These tasks tested preferences for social versus non-social stimuli, opposite-sex animals, isolated animals, and stressed animals. At the same time, we monitored behaviour and head movements using video tracking and motion sensors. We found that males and females showed distinct patterns of brain activity even before social interaction began, suggesting that the brain may enter different "anticipatory" states depending on sex. During social interaction, sex differences in neural activity varied depending on the social context and the stage of the interaction. The strongest and most consistent differences were observed in the basolateral amygdala, a brain region known to regulate emotional and social behaviour. Interestingly, these neural differences were linked to differences in movement dynamics and social responses, particularly during the first moments of interaction. Our findings suggest that sex shapes both baseline brain activity and the way the brain responds during social encounters. This work improves our understanding of the neural basis of sex differences in social behaviour and may help inform future research on psychiatric conditions that affect social functioning differently in males and females. HighllightsO_LISimultaneous multi-site recordings revealed sex-dependent neural dynamics across an amygdalo-striatal social brain network during social behaviour. C_LIO_LIMale and female mice exhibited distinct electrophysiological signatures even before social interaction, suggesting sex-specific anticipatory neural states. C_LIO_LIHigh-frequency local field potential oscillations showed the strongest and most consistent sex differences across behavioural contexts and brain regions. C_LIO_LIThe basolateral amygdala (BLA) emerged as a key region displaying context- and time-dependent sex differences during early social interaction. C_LIO_LISex-specific BLA activity correlated with movement dynamics during investigation of isolated conspecifics, linking neural network activity to behavioural responses. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/727611v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@82f8a7org.highwire.dtl.DTLVardef@92d085org.highwire.dtl.DTLVardef@b7dc78org.highwire.dtl.DTLVardef@eb4dba_HPS_FORMAT_FIGEXP M_FIG C_FIG

Rationale: Early life stress (ELS) is acknowledged to underlie cognitive and emotional abnormalities linked to stress-related mood disorders. ELS can lead to persistent biases in how uncertain feedback is processed to affect the flexibility of decision-making. Objectives: (1) To investigate the effects of ELS on the flexibility of rats trained on a serial probabilistic reversal learning (PRL) task involving spurious positive and negative feedback. (2) To elucidate the involvement of the stress hormone corticosterone and the noradrenergic and serotonergic systems in modulating how ELS affects PRL. Methods: Male and female rats were intermittently separated from maternal care on postnatal days five to nineteen, inclusively. As adults, the same rats were trained on a deterministic reversal learning task involving certain rewarded or non-rewarded outcomes followed by a PRL task where correct and incorrect responses were rewarded on 80% and 20% of trials, respectively. Dose-dependent effects of the beta-blocker, propranolol, selective serotonin reuptake inhibitor, citalopram and corticosterone were subsequently determined. Results: ELS resulted in an increased responsivity to feedback, specifically in males making more win-stay responses following a reward, that was associated with an increased punishment learning rate. In both control and MS rats, propranolol increased feedback sensitivity, but delayed updating following a rule switch. In contrast, neither citalopram nor corticosterone significantly affected reversal learning. Conclusions: ELS is sufficient to cause persistent changes in how feedback is processed by male rats on a reversal learning task. Activation of beta-adrenergic receptors may be necessary for updating learned associations during decision-making involving uncertain feedback.