Infant ultrasonic vocalizations predict adolescent social behavior in rats: Effects of early life adversity

Abstract

Early life adversity (ELA) increases risk for psychopathologies that often manifest during adolescence and involve disrupted social functioning. ELA affects development of the prefrontal cortex (PFC), which plays a role in social behavior. PFC oxytocin and vasopressin are important regulators of, first, mother-infant attachment, and, later, social behavior, and are implicated in psychiatric disorders. Here, we tested whether infant social communication is predictive of PFC development and adolescent social behavior. We used the limited bedding (LB) ELA model in rats during postnatal days (P)2-14, and measured isolation-induced ultrasonic vocalizations (USVs) at P10 to characterize differences in an early social response. Rats were tested for dyadic social interaction in adolescence (P34). Adolescent oxytocin receptor (Oxtr) and argininevasopressin receptor 1a mRNA were measured in the PFC. Relationships between infant USVs, adolescent behavior, and gene expression were assessed. LB-reared rats exhibited fewer USVs at P10. While social behaviors were not robustly affected by rearing, fewer total and complex-type infant USVs predicted fewer interactions in adolescence. LB increased Oxtr in both sexes but Oxtr was not directly predicted by USVs.Findings support the use of USVs as indicators of differential early life experience in rodents, toward further characterization of early factors associated with vulnerability.

Anxiety, aggression, reward sensitivity, and forebrain dopamine receptor expression in a laboratory rat model of early‐life disadvantage

“…We do not see anything obviously different about the methods in our study or those reporting more pup‐directed behavior after bedding restriction and the studies that found less caregiving. One possibility was that three of the studies reporting more pup‐directed behavior found it mostly or only during the animals’ dark photophase (Eck et al., 2020; Granata et al., 2022; McLaughlin et al., 2016), but here we report greater pup‐directed behavior during the light photophase, when early‐postpartum rats spend most of their time with the pups. We did not conduct mother–litter observations during the dark photophase, so do not know if our effects extended into that period of the light cycle.…”

“…This variable was calculated by summing the frequencies of hovering over the litter; licking, sniffing, and carrying the pups; and nursing the pups in any posture. A number of other studies involving laboratory rats and mice have also found that dams with restricted bedding, either using the Limited Bedding & Nesting paradigm or the Scarcity paradigm, spend more time interacting with their litters (Eck et al., 2020; Gallo et al., 2019; Granata et al., 2022; McLaughlin et al., 2016; Shupe & Clinton, 2021). We do not see anything obviously different about the methods in our study or those reporting more pup‐directed behavior after bedding restriction and the studies that found less caregiving.…”

“…Lastly, studies involving bedding and nesting scarcity have involved differing durations of treatment including chronically for the first week or so postpartum (e.g., Moriceau et al., 2009; Roth et al., 2009), chronically for days 8–12 postpartum (e.g., Raineki et al., 2015), and chronically for most of the first 2 weeks postpartum (e.g., Granata et al., 2022; Lapp et al., 2020). Similarly, rodent studies of early‐life lead exposure treat dams during pregnancy, during lactation, or both.…”

“…Despite methodological differences, many groups report these manipulations disturb maternal caregiving, specifically resulting in more fragmented behavioral sequencing, rough handling of the pups, and less time spent with the litter (Orso et al, 2019;Walker et al, 2017; more recently see Gallo et al, 2019;Laguna et al, 2022;Raineki et al, 2019;Rincón-Cortés & Grace, 2022;Rupasinghe et al, 2022;Scarola et al, 2020). Other studies, however, have instead found that dams with restricted bedding spend more time or greater frequency interacting with their pups (Eck et al, 2020;Gallo et al, 2019;Granata et al, 2022;McLaughlin et al, 2011;Shupe & Clinton, 2021). Regarding the developing offspring, these disruptions in maternal care compromise their ability to optimally huddle, resulting in altered thermoregulation and metabolism (Lapp et al, 2020) as well as disrupted hypothalamic-pituitary-adrenal axis function, altered anxiety, and atypical spatial or working memory when they reach young adulthood (Arp et al, 2016;Bath et al, 2017;Dalle Molle et al, 2012;Guadagno et al, 2018;Malter Cohen et al, 2013;Maniam et al, 2016;Rice et al, 2008;Rocha et al, 2021;Wang et al, 2011;Wang et al, 2012).…”

Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction

“…A distinct type of USV is emitted when rats experience aversive events, such as maternal separation as pups (Granata et al, 2022; Wöhr & Schwarting, 2008), and exposure to fear conditioning (Borta et al, 2006; Wöhr et al, 2005; Yee et al, 2012) or a context associated with a predator odor (Fendt et al, 2018) in adults. These calls are relatively long with a principal frequency of 22 kHz (Fig 2A), and will be referred to here as “alarm calls”.…”