Effects of prenatal alcohol exposure on social competence: Asymmetry in play partner preference among heterogeneous triads of male and female rats.

Social behavior deficits associated with prenatal alcohol exposure (PAE) are frequently described in terms of impaired social competence, which can be defined as the effectiveness in social interaction and the ability to employ social skills successfully within different interpersonal contexts. Play behavior-which peaks during adolescence-is critical for developing social competence, as well as for motor, cognitive, and emotional development. Studies of play behavior typically utilize protocols where animals interact in dyads. However, less is understood about how the social environment may shape PAE-related social behavior deficits, particularly in more complex social contexts. Here, we assess play partner preference utilizing a novel approach in which adolescent male and female animals interact within same-sex triads comprised of animals from mixed prenatal treatments to determine how play partner identity and social group composition interact to shape behavior. When triads included one PAE animal and two control animals (i.e., control animals had the option to play either with a fellow control or a PAE playmate), we observed play target asymmetry whereby controls preferentially played with fellow controls. Notably, these results were consistent for triads of both males and females, with subtle differences in frequency of initiations versus reciprocations. We found no play target asymmetry, however, when triads included two PAE animals and one control animal or different configurations of control and pair-fed animals. Taken together, play target asymmetry resulting from ineffective social interactions, including a failure to engage with, respond to, and/or solicit play from control play partners appropriately, suggests that PAE negatively impacts the development of social competence.

Prenatal alcohol exposure disrupts male adolescent social behavior and oxytocin receptor binding in rodents.

Social behavior deficits resulting from prenatal alcohol exposure (PAE) emerge early in life and become more pronounced across development. Maturational changes associated with adolescence, including pubertal onset, can have significant consequences for social behavior development, making adolescence a unique period of increased vulnerability to social behavior dysfunction. Unfortunately, little is known about the underlying neurobiology supporting PAE-related social behavior impairments, particularly in the context of adolescence, when the transition to a more complex social environment may exacerbate existing deficits in social behavior function. Here we perform a comprehensive evaluation of social behavior development in PAE animals during two different periods in adolescence using three separate but related tests of social behavior in increasingly complex social contexts: the social interaction test, the social recognition memory test (i.e. habituation-dishabituation test), and the social discrimination test. Additionally, we investigated the underlying neurobiology of the oxytocin (OT) and vasopressin (AVP) systems following PAE, given their well-documented role in mediating social behavior. Our results demonstrate that compared to controls, early adolescent PAE animals showed impairments on the social recognition memory test and increased OT receptor binding in limbic networks, while late adolescent PAE animals exhibited impairments on the social discrimination test and increased OTR binding in forebrain reward systems. Taken together, these data indicate that PAE impairs adolescent social behavior - especially with increasing complexity of the social context - and that impairments are associated with altered development of the OT but not the AVP system.

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health.

The effects of supplemental instruction derived from peer leaders on student outcomes in undergraduate human anatomy.

Supplemental instruction (SI) confers student success, as represented by grades, knowledge retention, and student engagement. However, studies often report professional, not undergraduate, program findings. To measure these effects, students studying human anatomy at a university in Ontario, Canada, attended structured (peer-assisted) or unstructured (nonpeer-assisted) SI sessions and completed a pre-/post-survey. Fifty-eight learners (39 systems (SYS) and 19 musculoskeletal (MSK) anatomy) completed both surveys and had responses analyzed. Both cohorts, maintained initial perceptions across pre-/post-analyses (MSK p = 0.1376 and SYS p = 0.3521). Resource usage was similar across both cohorts with discrepancies in skeletal model and textbook use. No MSK learner ranked any lab resources as "not at all useful." MSK learners felt more prepared to write a graded assessment (p = 0.0269), whereas SYS learners did not (p = 0.0680). Stratification of learners in MSK and SYS revealed learners spending between 30 and 60 min in SI sessions during the study period had the highest grades compared to students who spent less than 30 (p = 0.0286) or more than 60 (p = 0.0286) min attending SI sessions, respectively. Most learners in MSK (89.4%) and SYS (66%) concluded that they preferred structured over unstructured SI. Sentiment/thematic analysis using a generative AI-driven large language model revealed learners held positive perceptions of SI, emphasizing structured learning, resources, personalized learning, and support offered as the most prevalent themes surrounding SI. Ultimately, this study provides evidence that supports SI for improving student outcomes related to perceived preparedness for completing assessments and preferred teaching/learning styles in undergraduate human anatomy.

Impact of the COVID-19 pandemic on adults with Fetal Alcohol Spectrum Disorder: linking immune function to mental health status.

Prenatal alcohol exposure (PAE) is known to cause a variety of cognitive, behavioral, and neurological changes. Importantly, mental health problems are also overrepresented in individuals with Fetal Alcohol Spectrum Disorder (FASD), the group of neurodevelopmental conditions that can occur following PAE. Approximately 90% of individuals with FASD report experiencing mental health problems over their lifespan, compared to approximately 30% in the overall population. Individuals with FASD also display impairments in coping skills and increased vulnerability to stress. Here, we investigated whether the COVID-19 pandemic would have a differential impact on mental health and inflammation-to-mood associations in adults with FASD, compared to unexposed controls (no PAE). We capitalized on our pre-pandemic study examining health and immune function and invited past-participants to enroll in the current study. Participants completed mental health assessments and COVID-related questionnaires by phone. In addition, blood samples collected at baseline (pre-pandemic) were used to probe for inflammation-to-mood associations. Overall, our results indicate that lower SES was predictive of higher coronavirus anxiety scores, with no differences between adults with FASD and controls. In addition, while there were no differences in depression or anxiety measures at baseline (pre-pandemic) or during the pandemic, examination of inflammation-to-mood associations identified differential relationships in adults with FASD compared to unexposed controls. Specifically, there was a positive association between baseline neutrophil counts and both baseline and pandemic mental health scores in unexposed controls only. In addition, for unexposed controls there was also a negative association between baseline interferon-É£ (IFN-É£) and pandemic mental health scores. By contrast, only adults with FASD showed positive associations between baseline interleukin-12p70 (IL-12p70), IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) and pandemic mental health scores. Taken together, to our knowledge, this study is the first to examine the impact of the pandemic in adults with FASD. And while it may be too soon to predict the long-term effects of the pandemic on mental health, our data suggest that it will be important that future work also takes into account how immune function may be modulating mental health outcomes in this population.

Altered social recognition memory and hypothalamic neuropeptide expression in adolescent male and female rats following prenatal alcohol exposure and/or early-life adversity.

Prenatal alcohol exposure (PAE) and early-life adversity (ELA) both negatively impact social neurobehavioral development, including social recognition memory. Importantly, while individuals with PAE are more likely to experience ELA, relatively few studies have assessed the interaction of these two early insults on adolescent social behavior development. Here, we combine animal models of PAE and ELA to investigate both their unique and interactive effects on social neurobehavioral function in early and late adolescent male and female rats. Behavioral testing was followed by assessment of hypothalamic expression of oxytocin (OT) and vasopressin (AVP), key neuropeptides in the regulation of social behavior. Our results indicate that PAE and ELA have unique sex- and age-specific effects on social recognition memory and OT/AVP expression, with more pronounced neurobehavioral changes observed in males than in females in both early and late adolescence. Specifically, ELA impaired social recognition in early adolescent females regardless of prenatal treatment, while males showed deficits in both early and late adolescence in response to unique and interactive effects of PAE and ELA. Neurobiological data suggest that these perinatal insults differentially impact the OT and AVP systems in a sexually dimorphic manner, such that the OT system appears to be particularly sensitive to PAE in males while the AVP system appears to be more vulnerable to ELA in females. Taken together, our data provide novel insight into how the early postnatal environment may mediate outcomes of PAE as well as the power of animal models to interrogate the relationship between these pre- and postnatal insults.

Functional emergence of the hippocampus in context fear learning in infant rats.

The hippocampus is a part of the limbic system and is important for the formation of associative memories, such as acquiring information about the context (e.g., the place where an experience occurred) during emotional learning (e.g., fear conditioning). Here, we assess whether the hippocampus is responsible for pups' newly emerging context learning. In all experiments, postnatal day (PN) 21 and PN24 rat pups received 10 pairings of odor-0.5 mA shock or control unpaired odor-shock, odor only, or shock only. Some pups were used for context, cue or odor avoidance tests, while the remaining pups were used for c-Fos immunohistochemistry to assess hippocampal activity during acquisition. Our results show that cue and odor avoidance learning were similar at both ages, while contextual fear learning and learning-associated hippocampal (CA1, CA3, and dentate gyrus) activity (c-Fos) only occurred in PN24 paired pups. To assess a causal relationship between the hippocampus and context conditioning, we infused muscimol into the hippocampus, which blocked acquisition of context fear learning in the PN24 pups. Muscimol or vehicle infusions did not affect cue learning or aversion to the odor at PN21 or PN24. The results suggest that the newly emerging contextual learning exhibited by PN24 pups is supported by the hippocampus.

Enduring effects of infant memories: infant odor-shock conditioning attenuates amygdala activity and adult fear conditioning.

BACKGROUND: Early life adverse experience alters adult emotional and cognitive development. Here we assess early life learning about adverse experience and its consequences on adult fear conditioning and amygdala activity. METHODS: Neonatal rats were conditioned daily from 8-12 days-old with paired odor (conditioned stimulus, CS) .5mA shock, unpaired, odor-only, or naive (no infant conditioning). In adulthood, each infant training group was divided into three adult training groups: paired, unpaired or odor-only, using either the same infant CS odor, or a novel adult CS odor without or with the infant CS present as context. Adults were cue tested for freezing (odor in novel environment), with amygdala (14)C 2-DG autoradiography and electrophysiology assessment. RESULTS: Infant paired odor-shock conditioning attenuated adult fear conditioning, but only if the same infant CS odor was used. The (14)C 2-DG activity correlated with infant paired odor-shock conditioning produced attenuated amygdala but heightened olfactory bulb activity. Electrophysiological amygdala assessment further suggests early experience causes changes in amygdala processing as revealed by increased paired-pulse facilitation in adulthood. CONCLUSIONS: This suggests some enduring effects of early life adversity (shock) are under CS control and dependent upon learning for their impact on later adult fear learning.

Transitions in sensitive period attachment learning in infancy: the role of corticosterone.

Survival of altricial infants, including humans and rats, depends on attachment to the caregiver - a process that requires infants to recognize, learn, and remember their attachment figure. The demands of a dynamic environment combined with a maturing organism require frequent neurobehavioral reorganization. This restructuring of behavior and its supporting neural circuitry can be viewed through the unique lens of attachment learning in rats in which preference learning is enhanced and aversion learning is attenuated. Behavioral restructuring is well adapted to securing the crucial infant-caregiver relationship regardless of the quality of care. With maturation and the end of the infant-caregiver attachment learning period, the complex interplay of neural structures, hormones, and social behavior coordinates the developing rat's eventual transition to life outside of the nest. Nevertheless, early-life environmental and physiological stressors can alter the resilient nature of this system, particularly with respect to the amygdala, and these changes may provide important clues to understanding the lasting effects of early stress.