Infant Trauma Alters Social Buffering of Threat Learning: Emerging Role of Prefrontal Cortex in Preadolescence

Abstract

Within the infant-caregiver attachment system, the primary caregiver holds potent reward value to the infant, exhibited by infants’ strong preference for approach responses and proximity-seeking towards the mother. A less well-understood feature of the attachment figure is the caregiver’s ability to reduce fear via social buffering, commonly associated with the notion of a “safe haven” in the developmental literature. Evidence suggests this infant system overlaps with the neural network supporting social buffering (attenuation) of fear in the adults of many species, a network known to involve the prefrontal cortex (PFC). Here, using odor-shock conditioning in young developing rats, we assessed when the infant system transitions to the adult-like PFC-dependent social buffering of threat system. Rat pups were odor-shock conditioned (0.55 mA–0.6 mA) at either postnatal day (PN18; dependent on mother) or 28 (newly independent, weaned at PN23). Within each age group, the mother was present or absent during conditioning, with PFC assessment following acquisition using 14 C 2-DG autoradiography and cue testing the following day. Since the human literature suggests poor attachment attenuates the mother’s ability to socially buffer the infants, half of the pups at each age were reared with an abusive mother from PN8–12. The results showed that for typical control rearing, the mother attenuated fear in both PN18 and PN28 pups, although the PFC [infralimbic (IL) and ventral prelimbic (vPL) cortices] was only engaged at PN28. Abuse rearing completely disrupted social buffering of pups by the mother at PN18. The results from PN28 pups showed that while the mother modulated learning in both control and abuse-reared pups, the behavioral and PFC effects were attenuated after maltreatment. Our data suggest that pups transition to the adult-like PFC social support circuit after independence from the mother (PN28), and this circuit remains functional after early-life trauma, although its effectiveness appears reduced. This is in sharp contrast to the effects of early life trauma during infancy, where social buffering of the infant is more robustly impacted. We suggest that the infant social buffering circuit is disengaged by early-life trauma, while the adolescent PFC-dependent social buffering circuit may use a safety signal with unreliable safety value.

Elevated infant cortisol is necessary but not sufficient for transmission of environmental risk to infant social development: Cross-species evidence of mother–infant physiological social transmission

“…This CORT blockade switches off the amygdala and the pup's fear response to threat, as well as the pup's fear learning: the infant rat pup's amygdala is uniquely dependent upon CORT to function (Barr et al, 2009; Moriceau, Wilson, Levine, & Sullivan, 2006). This buffering process wanes as pups mature and prepare for independence (Opendak et al, 2019; Robinson-Drummer et al, 2019). In humans, maternal presence during an aversive conditioning procedure has similarly been shown to block threat learning in children, with the strongest effects noted among children with the lowest CORT levels (Tottenham et al, 2019).…”

“…Animal models of scarcity-adversity have also been used to experimentally demonstrate that environmental scarcity causally produces elevated CORT in mother rats and infant pups (Ivy, Brunson, Sandman, & Baram, 2008; Perry, Finegood, et al, 2019b; Raineki, Moriceau, & Sullivan, 2010; Raineki, Morgan, Ellis, & Weinberg, 2019), with subsequent disruption of neurobehavioral developmental outcomes (Avishai-Eliner, Gilles, Eghbal-Ahmadi, Bar-El, & Baram, 2001; Bale et al, 2010; Baram et al, 2012; Doherty, Blaze, Keller, & Roth, 2017; Junod, Opendak, LeDoux, & Sullivan, 2019; Perry et al, 2019a; Perry et al, 2019b; Perry et al, 2019c; Raineki, Rincón-Cortés, Belnoue, & Sullivan, 2012; Rincón-Cortés et al, 2015; Rincón-Cortés & Sullivan, 2016; Robinson-Drummer et al, 2019; Sevelinges et al, 2007; Walker et al, 2017). Taken together, these studies support the idea that chronically elevated CORT in infants and children may be one mechanism by which poverty-related adversity “gets under the skin” to influence child development.…”

Neural meaning making, prediction, and prefrontal–subcortical development following early adverse caregiving

“…For example, crEA (via parental separation and institutional caregiving) is followed by atypical responding of the amygdala and mPFC to parental cues (Callaghan et al, 2019b; Olsavsky et al, 2013). Rodent models of both abuse (fear conditioning) and insufficient bedding paradigms (which increase abusive physical treatment and decreased time with mother) have similarly been associated with altered neural responses to the mother in pups (Opendak et al, 2020; Raineki, Cortés, Belnoue, & Sullivan, 2012; Robinson-Drummer et al, 2019) – typically alterations in amygdala function appear developmentally earlier, which is then followed by aberrant responses in the mPFC responses at older ages (Robinson-Drummer et al, 2019). This last finding is consistent with the model presented in Figure 1 showing that the parental cue activates subcortical learning systems developmentally earlier than mPFC.…”

Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

“…Her group traced this effect to a temporary drop in dopamine in the basolateral complex when the mother was present (Barr et al, 2009). More recently, her group found that developmental maturation of the infralimbic cortex->amygdala pathway supplants this effect (Robinson-Drummer et al, 2019), such that "social buffering" by mother beyond the critical period induces a negative correlation between amygdala and VTA activation using PET imaging (Opendak et al, 2019). In contrast, maternal maltreatment due to resource scarcity closes the window such that maternal presence no longer deactivates amygdala within the critical period and at later ages maternal presence (perhaps appropriately) no longer deactivates the amygdala, nor does it produce the negative coupling of basolateral amygdala and VTA that would indicate convergent safety signals from BA25 and basomedial amygdala.…”