Neurobiology of maternal regulation of infant fear: the role of mesolimbic dopamine and its disruption by maltreatment

Abstract

Child development research highlights caregiver regulation of infant physiology and behavior as a key feature of early life attachment, although mechanisms for maternal control of infant neural circuits remain elusive. Here we explored the neurobiology of maternal regulation of infant fear using neural network and molecular levels of analysis in a rodent model. Previous research has shown maternal suppression of amygdala-dependent fear learning during a sensitive period. Here we characterize changes in neural networks engaged during maternal regulation and the transition to infant self-regulation. Metabolic mapping of 2deoxyglucose uptake during odor-shock conditioning in postnatal day (PN)14 rat pups showed that maternal presence blocked fear learning, disengaged mesolimbic circuitry, basolateral amygdala (BLA), and plasticity-related AMPA receptor subunit trafficking. At PN18, when maternal presence only socially buffers threat learning (similar to social modulation in adults), maternal presence failed to disengage the mesolimbic dopaminergic system, and failed to disengage both the BLA and plasticity-related AMPA receptor subunit trafficking. Further, maternal presence failed to block threat learning at PN14 pups following abuse, and mesolimbic dopamine engagement and AMPA were not significantly altered by maternal presence-analogous to compromised maternal regulation of children in abusive relationships. Our results highlight three key features of maternal regulation: (1) maternal presence blocks fear learning and amygdala plasticity through age-dependent suppression of amygdala AMPA receptor subunit trafficking, (2) maternal presence suppresses engagement of brain regions within the mesolimbic dopamine circuit, and (3) early-life abuse compromises network and molecular biomarkers of maternal regulation, suggesting reduced social scaffolding of the brain.

Adverse caregiving in infancy blunts neural processing of the mother

“…Indeed, corticosterone effects on amygdala plasticity are known to be noradrenaline-dependent 65 and amygdala-cortical pathways involved in processing of the maternal cue are impacted by maternal maltreatment, suggesting the noradrenergic-hypothalamic-pituitary-adrenal interface may provide a useful starting point for understanding the mechanisms for the observed effects. Overall, these data suggest altered processing of the maternal cue, which is supported by other studies showing degraded neural processing of maternal inputs following trauma 30,33,66 .…”

Adverse caregiving in infancy blunts neural processing of the mother: Translating across species

“…Indeed, corticosterone effects on amygdala plasticity are known to be noradrenaline-dependent 79,80 and amygdala-cortical pathways involved in processing of the maternal cue are impacted by maternal maltreatment 81 , suggesting the noradrenergic-HPA interface may provide a useful starting point for understanding the mechanisms for the observed effects. Overall, these data suggest altered processing of the maternal cue, which is supported by other studies showing degraded neural processing of maternal inputs following trauma 44,48,82 .…”

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

“…This phenomenon of social buffering of threat by the parent was first demonstrated in infant rats when the presence of the mother reduced the young infants’ responses to shock and blocked stress hormone release. This system is strongly phylogenetically represented and has been shown in rodents (Stanton and Levine, 1985; Levine et al, 1988; Suchecki et al, 1993; Hennessy et al, 2006, 2009, 2015; Gunnar et al, 2015; Sullivan and Perry, 2015; Al Aïn et al, 2017; Opendak et al, 2019), nonhuman primates and children (Coe et al, 1978; Wiener et al, 1987; Nachmias et al, 1996; Hennessy et al, 2009; Tottenham et al, 2012, accepted; Gee et al, 2013a; Sanchez et al, 2015; Howell et al, 2017). This social buffering supports the role of the attachment figure as a regulator of the immature infant (Bowlby, 1982; Hofer, 1994; Sroufe, 2005; Blair and Raver, 2015; Chambers, 2017; Feldman, 2017; Perry et al, 2017).…”

“…We have some understanding of the neural network supporting infant social buffering. This system involves caregiver suppression of the paraventricular nucleus (PVN) of the hypothalamus to block engagement of the stress axis (Shionoya et al, 2007) and attenuation of the amygdala and ventral tegmental response to threat (Hennessy et al, 2006, 2009; Moriceau and Sullivan, 2006; Moriceau et al, 2006, 2009; Opendak et al, 2019). This network analysis has, in part, been replicated in children (Gee et al, 2014; Tottenham et al, accepted), and nonhuman primates (Gunnar et al, 2015; Sanchez et al, 2015; Howell et al, 2017).…”

“…This network analysis has, in part, been replicated in children (Gee et al, 2014; Tottenham et al, accepted), and nonhuman primates (Gunnar et al, 2015; Sanchez et al, 2015; Howell et al, 2017). Importantly, the literature across these species suggests that social buffering by maternal presence is disrupted in mother-infant dyads with poor quality attachment (Nachmias et al, 1996; Gunnar and Quevedo, 2007; Hostinar et al, 2014; Gunnar et al, 2015; Sanchez et al, 2015; Gunnar and Sullivan, 2017; Opendak et al, 2019). Yet, the neurobiology of this compromised social buffering system has received little attention.…”