Early life stress and infant ultrasonic vocalizations as indicators of long-term affective processes in rats

Early life stress (ELS) takes a crucial role in shaping long-term behavioral and physiological processes, and maternal separation (MS) is a well-established rodent model of ELS. Ultrasonic vocalizations (USVs) are closely linked to the emotional states of animals; however, the predictive value of infant USVs for subsequent affective processes remains poorly understood, especially in relation to ELS. The present thesis examines the behavioral and neurobiological effects of MS in Wistar rats across adolescence and adulthood, while investigating the predictive potential of pup USVs on measured outcomes. A repeated MS procedure was employed during postnatal days (PND) 2–14 followed by a maternal potentiation test with USV recordings on PND 15. Animals were subjected to a range of behavioral evaluations including anxiety-like and social behaviors during adolescence (PND 35–36) and adulthood (PND 80–87), along with additional measurements of anhedonia and fear conditioning in adulthood. At the end of behavioral testing, corticosterone release and neuronal activation in several limbic regions were assessed following restraint stress. MS reduced infant USVs, suppressed social and anxiety-like behavior in adolescence, and led to impairments in hedonic response and fear memory in adulthood, associated with decreased stress-related activation in the lateral amygdala. Infant USVs inversely predicted anxiety-like behavior in adolescence for both groups, while relating with neuronal activation in habenula in control, but not MS animals. These results show that pup USVs not only reflect early stressful experiences but also possess a predictive value for subsequent affective processes.