Dissertation Defense - Amanda White

Award Date

Thursday, June 17, 2021

Recipient

Maternal Buffering of Infant’s Fear In Typically Developing Rats and In A Rat Model for A Psychiatric Disorder

Dr. Jacek Debiec, Chair

Social buffering is broadly defined as an individual’s ability to suppress the physiological, behavioral, and/or emotional consequences of adverse events in another individual. A particularly potent and vital form of social buffering is caregiver buffering, which protects the developing infant brain from the deleterious effects of stress. Rodent work has provided valuable information about the behavioral, endocrine, and neurobiological mechanisms of maternal regulation of threat and how those mechanisms may be altered by early life experiences. The ability of infant rats to acquire Pavlovian odor-shock associations generally emerges when they are about ten days old, but is under tight regulation by the mother. Previous studies have shown that when infant rats underwent an odor-shock Pavlovian threat learning experience in the presence of an anesthetized mother, they did not avoid the conditioned odor when tested, unlike pups conditioned without maternal presence. This behavioral effect was, in part, mediated by the mother’s ability to suppress the infant rat’s stress response and amygdala reactivity during the threat learning experience. Follow-up studies have shown that disruption of the relationship between mother and infant can affect the ability of the mother to regulate fear in her infants. In this thesis, I address several remaining questions about the functions and underlying mechanisms of maternal buffering in infant rats. In Chapter 1, I briefly review the existing human and rat literature on caregiver regulation of stress, threat learning, and neural activity and review the trajectory of infant rat development. In Chapter 2, I demonstrate that the effect of maternal presence during a threat learning experience can be observed using a robustly studied defense response – threat conditioned-induced freezing – and that female infant rats may be more susceptible to maternal buffering of freezing than male infant rats. In Chapter 3, I examine the functional networks engaged by infant rats conditioned with and maternal presence and apply graph theory to analyze patterns of immediate early gene expression. Overall functional connectivity was significantly increased in pups conditioned with maternal presence. A graph theoretical analysis revealed that the network engaged by pups conditioned with maternal presence was more integrated and lacked distinctive hubs; in contrast, the network engaged by pups conditioned without maternal presence was more segregated and had distinct hubs: the lateral amygdaloid nucleus, dorsolateral part, basolateral amygdaloid nucleus, anterior part, and medial amygdaloid nucleus, anterior dorsal part. In Chapter 4, I examine the ontogeny of threat learning and stress responsivity in a vulnerable phenotype prone to high-anxiety like behavior in adulthood, and then question whether maternal presence and fibroblast growth factor 2 are capable of regulating threat learning in these animals. In Chapter 5, I summarize results from each chapter and discuss future directions. The findings outlined in this thesis provide an important next step in characterizing maternal buffering and illuminate exciting topics for future inquiry.