Abuse in early childhood often leads to depression, although typically not expressed until later in life. How child abuse alters the trajectory of brain development to produce a vulnerability to depression is incompletely understood. We propose to study an experimental model of parental abuse in rats where abuse during a sensitive period in infancy produces disrupted social behavior, increased immobility in a Forced Swim Test (FST) animal model of depression, and amygdala dysfunction. In this proposal we focus on the effects of abuse during infancy and early life on both behavior and brain (amygdala, prefrontal cortex).
In Aim 1 we questions if there is a sensitive period of vulnerability to abuse to cause depressive-like behaviors? Aim 2 we ask if the ontogeny of the amygdala or neural circuits activated during social behavior or FST in developing rats is altered by early life abuse.
In Aim 3 we question if the amygdala or prefrontal cortex or its connectivity to the PFC, which are brain areas strongly impacted by early life trauma, contribute to the behavioral dysfunction following early life abuse. The innovation and significance of our proposed work is that we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms. We will question how the infant brain's response to perturbation can differ depending on the time and context of perturbation and question how these experiences alter infant behaviors. This approach will enable us to not only identify infant events that contribute to later life dysfunction but also explore unique behavior and neural changes in the infant to predict later life dysfunction. We will use infants'well-defined sensitive periods for caregiver-attachment learning and infants'unique neurobehavioral response to trauma (maltreatment from mother or more controlled shock) during each period. Furthermore, this work also highlights the strong influence of social interactions and social cues (reared by abusive mother or shock with/without mother) during clearly defined sensitive periods. Indeed, our published data has begun to suggest that the infants'immediate neural response to trauma is dramatically different from the adults'but importantly, that it further differs depending on whether the mother is present.
Adverse experiences during childhood, such as abuse/trauma, increases the incidence of depression in later life. To better understand how this experience alters later life mental health, we use a Sensitive Period model that incorporates how the timing of perturbation (abuse) and context of perturbation (presence or absence of mother) interacts with maturational processes to enhance vulnerability to later life depressive-like symptoms.
|Perry, Rosemarie E; Finegood, Eric D; Braren, Stephen H et al. (2018) Developing a neurobehavioral animal model of poverty: Drawing cross-species connections between environments of scarcity-adversity, parenting quality, and infant outcome. Dev Psychopathol :1-20|
|Perry, Rosemarie E; Blair, Clancy; Sullivan, Regina M (2017) Neurobiology of infant attachment: attachment despite adversity and parental programming of emotionality. Curr Opin Psychol 17:1-6|
|Opendak, Maya; Gould, Elizabeth; Sullivan, Regina (2017) Early life adversity during the infant sensitive period for attachment: Programming of behavioral neurobiology of threat processing and social behavior. Dev Cogn Neurosci 25:145-159|
|Rickenbacher, Elizabeth; Perry, Rosemarie E; Sullivan, Regina M et al. (2017) Freezing suppression by oxytocin in central amygdala allows alternate defensive behaviours and mother-pup interactions. Elife 6:|
|Tallot, Lucille; Diaz-Mataix, Lorenzo; Perry, Rosemarie E et al. (2017) Updating of aversive memories after temporal error detection is differentially modulated by mTOR across development. Learn Mem 24:115-122|
|Debiec, Jacek; Sullivan, Regina M (2017) The neurobiology of safety and threat learning in infancy. Neurobiol Learn Mem 143:49-58|
|Al Aïn, Syrina; Perry, Rosemarie E; Nuñez, Bestina et al. (2017) Neurobehavioral assessment of maternal odor in developing rat pups: implications for social buffering. Soc Neurosci 12:32-49|
|Santiago, Adrienne; Aoki, Chiye; Sullivan, Regina M (2017) From attachment to independence: Stress hormone control of ecologically relevant emergence of infants' responses to threat. Curr Opin Behav Sci 14:78-85|
|Rincón-Cortés, M; Sullivan, R M (2016) Emergence of social behavior deficit, blunted corticolimbic activity and adult depression-like behavior in a rodent model of maternal maltreatment. Transl Psychiatry 6:e930|
|Perry, Rosemarie E; Al Aïn, Syrina; Raineki, Charlis et al. (2016) Development of Odor Hedonics: Experience-Dependent Ontogeny of Circuits Supporting Maternal and Predator Odor Responses in Rats. J Neurosci 36:6634-50|
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