RUI: Neural Basis of Pubertal Shifts in Stress Reactivity

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Puberty is a significant stage of development marked by transitions in both physiological and neural function. Though most people appreciate the hormonal changes that occur during this period, the types of experiences that an adolescent encounters also change dramatically. These experiences can result in increased exposure to stressors in the environment. A growing body of research indicates that how an individual responds to stress changes substantially during this stage, but we know little about the biological mechanisms that underlie these shifts. It is important to address these gaps in our understanding, because stress can disrupt body and brain systems that are developing into their adult-like patterns during this time. Using an experimental animal model that combines studies at the neuroanatomcial and biochemical levels, these experiments will begin to reveal the neural mechanisms that mediate the pubertal changes in stress responsiveness. The results of these studies will extend our understanding of how puberty and stress interact to affect both the brain and body. Importantly, these studies will be undertaken at Barnard College, an all women's liberal arts college. Thus, in addition to leading to advances in our understanding of neurodevelopment, support of this proposal will provide many female undergraduates with educational opportunities to take part in all aspects of experimental research.The paraventricular nucleus of the hypothalamus (PVN) plays a pivotal role in integrating information from brain areas that coordinate the stress response. Greater levels of neural activation have been found in the PVN of prepubertal compared to adult animals in response to stress, leading to the hypothesis that developmental changes in the connectivity and/or function of the PVN contribute to pubertal alterations in stress reactivity. This project will test this hypothesis by assessing pubertal differences in the connectivity, phenotype, and activation of brain areas that project to the PVN. Specifically, neural tract tracing combined with immunohistochemical markers of excitatory or inhibitory neurons will be used in prepubertal and adult rats exposed to stress. This project will also examine pubertal changes in excitatory and inhibitory signaling in the PVN by assessing receptor expression and measuring hormone levels following site-directed delivery of excitatory or inhibitory receptor modulators in the PVN of prepubertal and adult rats exposed to stress. These studies will probe neural mechanisms responsible for the pubertal transitions in stress reactivity, and provide information on how the adolescent and adult nervous systems differentially process stressful stimuli.