Development is a period of neurobehavioral changes requiring immature organisms to exhibit behavioral flexibility to adapt to the world. A traditional view of development sees existing brain circuits becoming more complex to accommodate behavioral change. While certainly sometimes true, additional research suggests that developing organisms must sometimes change the neural circuitry evoked by a specific event for expression of the more mature behavior. For example, as infants transition from dependence on the mother to independence, at least some new neural circuits will be required for new adaptive behaviors to be expressed. Yet we know little about these transitions, despite recent evidence suggesting these transitions are periods of vulnerability for initiation of pathways to pathology and developmental disorders. The purpose of this proposal is to explore developmental transitions using our model of infant rat learning. Specifically, we explore a brief 5 day period in developing rat pups when they rapidly transition between attachment learning and amygdala-dependent adult-like fear learning - both supported by odor-shock pairings - which learning system is engaged is controlled by maternal presence.
In Aim 1, we test the hypothesis that prefrontal cortical (PFC) subareas' development and their control by the mother contributes to pups' ability to transition between attachment learning and amygdala-dependent fear learning. We include analysis of individual PFC-amygdala brain areas but also use a novel analytical tool to assess functional connectivity - a technique similar to fMRI analysis to facilitte translational research.
Aim 2 extends these networks by testing causal roles of specific network nodes. Finally, Aim 3 examines the role of dopamine, an important modulator in PFC-amygdala function in these age- and context-dependent changes in behavioral flexibility over early development. This research has health relevance in at least two areas. First, this developmental approach assesses PFC and amygdala as individual brain areas, but also with functional connectivity analysis to go beyond defining the role of a brain area to expand our understanding of its role in a larger circuit to evoke adaptive behaviors. Indeed, both dysfunction of individual brain areas and disrupted functional connectivity have been implicated in myriad developmental disorders, including depression and ADHD. Second, this ecologically relevant approach highlights mother-infant interactions to better explain how maternal presence alters the child's behavior by expanding our understanding of how the caregiver alters brain function and neurobehavioral transitions.
Recent evidence suggests that the same event can engage different brain circuits at different ages with transitions between these circuits considered periods of vulnerability that can initiate a pathway to pathology. Yet, we have little understandin of how a child can switch between these circuits or why access to an early life circuit is lost. To address this gap, we propose to use a model system where two different circuits are evoked by the same event at two different ages, and a brief developmental period when both circuits co-exist and maternal presence controls which circuit is used.
|Boulanger-Bertolus, Julie; Rincón-Cortés, Millie; Sullivan, Regina M et al. (2017) Understanding pup affective state through ethologically significant ultrasonic vocalization frequency. Sci Rep 7:13483|
|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|
|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|
|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|
|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|
|Walker, Claire-Dominique; Bath, Kevin G; Joels, Marian et al. (2017) Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential. Stress 20:421-448|
|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:|
|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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