Memory of early maltreatment: Neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning

Department of Zoology, University of Oklahoma, Norman, Oklahoma 73019, USA.
Biological Psychiatry (Impact Factor: 10.26). 05/2005; 57(8):823-31. DOI: 10.1016/j.biopsych.2005.01.032
Source: PubMed


While children form an attachment to their abusive caregiver, they are susceptible to mental illness and brain abnormalities. To understand this important clinical issue, we have developed a rat animal model of abusive attachment where odor paired with shock paradoxically produces an odor preference. Here, we extend this model to a seminaturalistic paradigm using a stressed, "abusive" mother during an odor presentation and assess the underlying learning neural circuit.
We used a classical conditioning paradigm pairing a novel odor with a stressed mother that predominantly abused pups to assess olfactory learning in a seminaturalistic environment. Additionally, we used Fos protein immunohistochemistry to assess brain areas involved in learning this pain-induced odor preference within a more controlled maltreatment environment (odor-shock conditioning).
Odor-maternal maltreatment pairings within a seminatural setting and odor-shock pairings both resulted in paradoxical odor preferences. Learning-induced gene expression was altered in the olfactory bulb and anterior piriform cortex (part of olfactory cortex) but not the amygdala.
Infants appear to use a unique brain circuit that optimizes learned odor preferences necessary for attachment. A fuller understanding of infant brain function may provide insight into why early maltreatment affects psychiatric well-being.

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Available from: Regina Marie Sullivan, Mar 30, 2014
    • "Caregiver manipulations were performed as previously reported in our laboratory (Blaze & Roth, 2013; Blaze et al., 2013; Roth et al., 2014) and using a protocol adapted from others (Ivy et al., 2008; Raineki et al., 2010; Roth & Sullivan, 2005). Each experimental litter was split into three groups on PN1, with 3–4 male and female pups in each group. "
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    ABSTRACT: Infant–caregiver experiences are major contributing factors to neural and behavioral development. Research indicates that epigenetic mechanisms provide a way in which infant–caregiver experiences affect gene activity and other downstream processes in the brain that influence behavioral development. Our laboratory previously demonstrated in a rodent model that exposure to maltreatment alters methylation of DNA associated with the brain-derived neurotrophic factor (bdnf) and reelin genes as well as mRNA of key epigenetic regulatory genes in the medial prefrontal cortex (mPFC). In the current study, we characterized patterns of histone acetylation at bdnf and reelin gene loci after our caregiver manipulations. Using a within-litter design (n = 8–10/group from eight litters), pups were exposed to adverse (maltreatment condition: exposure to a stressed caregiver) or nurturing (cross-foster condition: exposure to a nurturing caregiver) caregiving environments outside the home cage for 30 min daily during the first postnatal week. Remaining pups in a litter were left with the biological mother during each session (providing normal care controls). We then used chromatin immunoprecipitation (ChIP) and quantitative RT-PCR to measure histone 3 lysine 9/14 acetylation associated with bdnf promoters I and IV and the reelin promoter in the adult mPFC. Maltreated females had decreased acetylation at bdnf IV, while neither males nor females exhibited histone acetylation alterations at bdnf I or reelin. These data demonstrate the ability of maltreatment to have long-term consequences on histone acetylation in the mPFC, and provide further evidence of the epigenetic susceptibility of bdnf IV to the quality of infant–caregiver experiences.
    No preview · Article · Aug 2015 · Stress (Amsterdam, Netherlands)
    • "For example, when rat pups are young and reliant upon maternal care for survival, they learn maternal odour preference to support attachment and feeding [46]. Prior to the age of P12, rat pups will paradoxically form an odour preference if an odour is paired with an aversive stimulus, a behaviour that is thought to promote maternal attachment in the face of adversity [47] [48] [49]. At around P10 when rat pups begin to explore the extra-nest environment for the first time [50], odour aversion learning begins to emerge, which coincides with engagement of the amygdala [51] [52]. "
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    ABSTRACT: Given the profound influence that early life experiences can have upon psychosocial functioning later in life, it is intriguing that most adults fail to recall autobiographical events from their early childhood years. Infantile amnesia is the term used to describe this phenomenon of accelerated forgetting during infancy, and it is not unique to humans. Over the years, information garnered from animal studies has provided clues as to the neurobiological basis of infantile amnesia. The purpose of this review is to provide a neurobiological update on what we now know about infantile amnesia since the publication of Campbell and Spear's seminal review on the topic more than 40 years ago. We present evidence that infantile amnesia is unlikely to be explained by a unitary theory, with the protracted development of multiple brain regions and neurotransmitter systems important for learning and memory likely to be involved. The recent discovery that exposure to early life stress can alleviate infantile amnesia offers a potential explanation as to how early adversity can so profoundly affect mental health in adulthood, and understanding the neurobiological basis for this early transition may lead to the development of effective therapeutic interventions. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · Behavioural brain research
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    • ", milk , warmth , tactile stimulation – called stroking ) but also painful stimuli ( 0 . 5 mA shock , tail pinch ) ( Haroutunian & Campbell , 1979 ; Camp & Rudy , 2004 ; Roth & Sullivan , 2005 ; Sullivan et al . , 2000 ; Takahashi et al . "
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    ABSTRACT: Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. © 2014 Wiley Periodicals, Inc. Dev Psychobiol
    Full-text · Article · Dec 2014 · Developmental Psychobiology
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