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    • As mentioned above termination of the sensitive period

    2018-10-29

    As mentioned above, termination of the sensitive ace inhibitors for attachment at PN10 in typical rearing conditions is primarily due to increasing levels of CORT and functional emergence of the amygdala (Sullivan and Holman, 2010). While CORT levels naturally increase at PN10, the environment readily changes pups CORT levels, providing environmental control of the sensitive period for attachment termination. Specifically, increasing CORT during the sensitive period, either via rearing with an abusive mother, or through pharmaceutical manipulations (systemic injections or by intra-amygdala microinfusions), can prematurely end sensitive period learning. Indeed, the amygdala is mature enough to support threat learning in pups as young as PN6, provided sufficient levels of corticosterone are available within the amygdala (Debiec and Sullivan, 2014; Moriceau et al., 2004, 2009; Moriceau and Sullivan, 2004, 2006). Pups reared by an abusive mother during the SHRP receive CORT through her milk and her ability to socially buffer this CORT elevation is compromised; when these pups are trained on a peppermint odor-shock conditioning paradigm outside the nest at PN7, they will learn an aversion through amygdala-dependent mechanisms (Moriceau et al., 2004; Raineki et al., 2010b). Similarly, pups reared with a normal nurturing mother but trained on a 5-day odor-shock conditioning procedure during the SHRP will learn an aversion to the odor if they receive CORT injections before each training session (Raineki et al., 2010b,c). It is important to note that, although abused pups or pups injected with CORT can learn arbitrary odor aversions (eg. peppermint) via premature amygdala engagement, they will nevertheless always show a preference for the maternal odor. As will be discussed further, this preference accompanies a disordered, rather than typical, attachment. Although abuse and repeated odor-shock fails to produce an aversion to maternal odor, these manipulations generate latent changes in amygdala function that emerge around weaning age. Importantly, direct abuse from the caregiver and pairing of the maternal odor with shock produce indistinguishable neurobehavioral outcomes. Amygdala-dependent deficits are expressed in a task-specific manner: amygdala hyperactivity underlies decreased social exploration in adolescence and depressive and anxiety-like behavior in adulthood (Fig. 2), in parallel with impaired ability to learn aversions to threat and blunted amygdala activation during fear conditioning (Raineki et al., 2012; Sevelinges et al., 2007, 2011, 2008). These results parallel clinical studies showing a role for amygdala dysfunction in psychiatric sequelae in adults with a history of attachment trauma, resulting from abuse and/or neglect, during childhood (Callaghan et al., 2014; Teicher et al., 2003).
    Stress uncovers latent consequences of early-life trauma Across many species, many of the effects of infant abuse remain latent until peri-adolescence (Adriani and Laviola, 2004; Amaral, 2003; Andersen and Teicher, 2008; Bauman et al., 2006; Costello et al., 2003). For this reason, it can be difficult to identify abused children in the absence of physical evidence. In parallel with observations of latent abuse-related deficits in rodents and non-human primates, many of the effects of early life trauma on children’s mental health appear to be delayed until they begin to transition into adolescence (Bachevalier and Loveland, 2006; Bachevalier et al., 2001; Callaghan et al., 2014; Goursaud and Bachevalier, 2007; Goursaud et al., 2014; Machado and Bachevalier, 2003; Raper et al., 2014; Tottenham and Sheridan, 2009). However, stress can uncover deficits associated with trauma that may otherwise be hidden, as demonstrated by Mary Ainsworth’s Strange Situation Test. In this procedure, repeatedly removing children’s caregiver and introducing a stranger was necessary to reveal behavioral impairments marking disordered attachment (Ainsworth, 1969; Crittenden, 1992; Nachmias et al., 1996). This can also be modeled in rodents: pups that were exposed to abuse in the low bedding procedure and repeated odor-shock pairings form a disordered attachment to the mother, expressed in decreased approach behavior towards the maternal odor, less nipple attachment, and amygdala hyperactivity if given CORT injections before testing (Raineki et al., 2012). The CORT injection in pups models a high-stress environment, which appears necessary to uncover neurobehavioral deficits before weaning. Importantly, this CORT injection did not disrupt social interaction or activate the amygdala in pups reared with a nurturing mother, nor was there evidence of disordered attachment in pups that received only shock trauma or unpaired odor-shock training. Taken together, these findings suggest that repeatedly experiencing trauma associated with caregiver cues during the sensitive period for attachment has a unique neural signature, producing latent changes in amygdala function to program emotionality and social behavior throughout the lifespan.