The scheduling of adolescence with Netrin-1 and UNC5C.

Dopamine axons are the only axons known to grow during adolescence. Here, using rodent models, we examined how two proteins, Netrin-1 and its receptor, UNC5C, guide dopamine axons towards the prefrontal cortex and shape behaviour. We demonstrate in mice ( Mus musculus ) that dopamine axons reach the cortex through a transient gradient of Netrin-1 expressing cells - disrupting this gradient reroutes axons away from their target. Using a seasonal model (Siberian hamsters; Phodopus sungorus ) we find that mesocortical dopamine development can be regulated by a natural environmental cue (daylength) in a sexually dimorphic manner - delayed in males, but advanced in females. The timings of dopamine axon growth and UNC5C expression are always phase-locked. Adolescence is an ill-defined, transitional period; we pinpoint neurodevelopmental markers underlying this period.

Long-term consequences of peri-adolescent social isolation on social preference, anxiety-like behaviour, and vasopressin neural circuitry of male and female rats.

Social isolation during the juvenile and adolescent stages (peri-adolescent social isolation) can have long-term consequences for behavioural and neural development. Most of this research, however, has relied on data from males, and very few studies have included both sexes. The present study investigated the impact of peri-adolescent social isolation on social preference, anxiety-like behaviour, and vasopressin neural circuitry of male and female Long Evans rats. Rats were either housed alone for 3 weeks beginning at weaning (Isolated) or in groups (Group-housed). In adulthood, rats were tested in social preference, open field, marble burying, and light/dark box tests, and brains were processed for vasopressin immunohistochemistry. Isolated males exhibited a lower social preference score and spent more time in the light zone of the light/dark box than their group-housed counterparts. Isolated and Group-housed females did not differ in these measures. Peri-adolescent social isolation did not alter vasopressin fibre density in target areas known to influence social and anxiety-like behaviours (the lateral septum or lateral habenula), but increased fibre density in an output pathway of the circadian pacemaker (projections to the paraventricular nucleus of the thalamus); an effect detected across both sexes. A previously unreported sex difference was also detected for vasopressin fibre density in the paraventricular nucleus of the thalamus (females > males). These findings demonstrate long-term consequences of peri-adolescent social isolation on social preference, anxiety-like behaviour, and the circadian vasopressin pathway and suggest that socio-affective development of males is more vulnerable to social stressors during the juvenile and adolescent stages.

Photoperiod regulates hypothalamic miR-155 gene expression in female, but not male, Siberian hamsters (Phodopus sungorus).

In many species, seasonal changes in photoperiod regulate several behaviors and physiological systems, including reproduction, energy balance, and immune function. MicroRNAs (miRs) regulate numerous physiological processes and developmental transitions through translational repression and mRNA degradation. Their role in seasonal transitions has been vastly understudied, with only a few reports in animals. Furthermore, no study has assessed whether there are sex differences in seasonal regulation of miRs. miR-155 is a primary candidate for seasonal regulation because it influences immune responses, energetics, and reproductive function. In this study, we tested the hypothesis that photoperiod regulates miR-155 gene expression in Siberian hamsters and whether there were sex differences in this photoperiod regulation. miR-155 gene expression levels were measured in hypothalamus, hippocampus, and spleen of male and female Siberian hamsters reared in short days (SDs) or long days (LDs). As expected, SD-reared hamsters had significantly reduced body mass, lightened pelage color, and lower reproductive organ size than LD-reared hamsters. Notably, SDs increased hypothalamic miR-155 gene expression in females but not in males. No differences were observed in hippocampus and spleen of either sex. These findings demonstrate sex-specific photoperiod regulation of miR-155 gene expression. Future studies should consider possible sex differences in miR contributions to seasonal changes in physiology and behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Investigation of social, affective, and locomotor behavior of adolescent Brattleboro rats reveals a link between vasopressin's actions on arousal and social behavior.

Arginine vasopressin (AVP) has recently been implicated in juvenile and adolescent social development. How AVP influences social development, however, is not understood. Adolescent homozygous Brattleboro rats (Hom), which lack AVP due to a mutation in the Avp gene, exhibit fewer active social behaviors (e.g., social play) but more passive social behaviors (e.g., huddling) than their wild type and heterozygous (Het) littermates, raising the possibility that AVP impacts social development through an arousal mechanism. Here, we test whether the atypical social phenotype of adolescent Hom rats is associated with altered behavioral arousal, social approach, or affective behaviors and whether Brattleboro mothers impact these behavioral phenotypes. Male and female Het and Hom adolescents born to Het or Hom mothers were tested in social interaction, open field, novelty-seeking, social approach, and marble burying tests. As reported previously, Hom rats played less and emitted fewer 50 kHz ultrasonic vocalizations while huddling more than their Het littermates. No genotype differences were detected in novelty seeking or social approach, nor were consistent differences found between offspring from Het and Hom mothers. However, Hom rats were less active in the open field and buried fewer marbles than Het rats indicating a hypoaroused, low anxiety phenotype. Open field activity correlated with levels of social play indicating that the effects of the Brattleboro mutation on arousal and social behavior are linked. These data demonstrate that chronic AVP deficiency impacts behavioral arousal during adolescence and support the hypothesis that AVP influences adolescent social development, in part, through its regulation of arousal.