Impairments in identifying and responding to the emotions of others manifest in a variety of psychopathologies. Therefore, elaborating the neurobiological mechanisms that underpin social responses to social emotions, or social affective behavior, is a translationally important goal. The insular cortex is consistently implicated in stress-related social and anxiety disorders, which are associated with diminished ability to make and use inferences about the emotions of others to guide behavior. We investigated how corticotropin-releasing factor (CRF), a neuromodulator evoked upon exposure to stressed conspecifics, influenced the insula. We hypothesized that social affective behavior requires CRF signaling in the insular cortex in order to detect stress in social interactions. In acute slices from male and female rats, CRF depolarized insular pyramidal neurons. In males, but not females, CRF suppressed presynaptic GABAergic inhibition leading to greater excitatory synaptic efficacy in a CRF receptor 1 (CRF1)- and cannabinoid receptor 1 (CB1)-dependent fashion. In males only, insular CRF increased social investigation, and CRF1 and CB1 antagonists interfered with social interactions with stressed conspecifics. To investigate the molecular and cellular basis for the effect of CRF we examined insular CRF1 and CB1 mRNAs and found greater total insula CRF1 mRNA in females but greater CRF1 and CB1 mRNA colocalization in male insular cortex glutamatergic neurons that suggest complex, sex-specific organization of CRF and endocannabinoid systems. Together these results reveal a new mechanism by which stress and affect contribute to social affective behavior.

Caretaking stability in the early life environment supports neurobehavioral development, while instability and neglect constitute adverse environments that can alter maturational processes. Research in humans suggests that different types of early life adversity (ELA) can have differential effects on caretaker relationships and later cognitive and social development; however, identifying mechanistic underpinnings will require animal models with translational validity. Two common rodent models, maternal separation (MS) and limited bedding (LB), influence the mother-infant relationship during a critical window of development. We hypothesized that these paradigms may affect the development of communication strategies on the part of the pup. Ultrasonic vocalizations (USVs) are a care-eliciting mechanism and ethologically relevant response to stressors in the rat pup. USV emission rates and acoustic parameters change throughout early development, presenting the opportunity to define developmental milestones in USVs that would reflect neurobehavioral aberrations if disrupted. This study investigated the effects of MS or LB on the dam-pup relationship by quantifying pup USVs, maternal behavior, and the relationship between the two. First, we used a generalized additive model approach to establish typical developmental trajectories of USV acoustic properties and determine windows of change in MS or LB rearing. Additionally, we quantified maternal behaviors and the predictability of maternal care sequences using an entropy rate calculation. MS and LB each shifted the developmental trajectories of USV acoustic parameters and call types in a sex-specific manner. MS more often impacted male USVs, while LB impacted female USVs. MS dams spent more time passive nursing, and LB dams spent more time on the nest. The predictability of maternal care was associated with the rate of USV emissions exclusively in females. Taken together, findings demonstrate sex- and model-specific effects of rearing environments on a novel developmental trajectory involving the mother-infant relationship, facilitating the translation of animal ELA paradigms to assess later-life consequences.

Future long-duration space missions will involve travel outside of the Earth’s magnetosphere protection and will result in astronauts being exposed to high energy and charge (HZE) ions and protons. Exposure to this type of radiation can result in damage to the central nervous system and deficits in numerous cognitive domains that can jeopardize mission success. Social processing is a cognitive domain that is important for people living and working in groups, such as astronauts, but it has received little attention in terms of HZE ion exposure. In the current study, we assessed the effects of whole-body oxygen ion (16O; 1000 MeV/n) exposure (1 or 10 cGy) on social odor recognition memory in male Long-Evans rats at one and six months following exposure. Radiation exposure did not affect rats’ preferences for a novel social odor experienced during Habituation at either time point. However, rats exposed to 10 cGy displayed short and long-term deficits in 24-h social recognition. In contrast, rats exposed to 1 cGy only displayed long-term deficits in 24-h social recognition. While an age-related decrease in Ki67+ staining (a marker of cell proliferation) was found in the subventricular zone, it was unaffected by radiation exposure. At one month following exposure, plasma KC/GRO (CXCL1) levels were elevated in the 1 cGy rats, but not in the 10 cGy rats, suggesting that peripheral levels of this cytokine could be associated with intact social recognition at earlier time points following radiation exposure. These results have important implications for long-duration missions and demonstrate that behaviors related to social processing could be negatively affected by HZE ion exposure.