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Title:The role of puberty in the development of the adolescent rodent medial prefrontal cortex and behavior
Author(s):Drzewiecki, Carly Marie
Director of Research:Juraska, Janice M
Doctoral Committee Chair(s):Juraska, Janice M
Doctoral Committee Member(s):Gulley, Joshua; Raetzman, Lori; Liang, Nu-Chu
Department / Program:Neuroscience Program
Discipline:Neuroscience
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):adolescence
estrogen
cognition
testosterone
cortex
Abstract:Adolescence, the transitional period of development between childhood and adulthood, is typically defined in humans by its unique behavioral phenotype. Behaviorally, adolescents are emotional risk-takers who place increased emphasis on social interactions. Additionally, many psychiatric illnesses onset during adolescence in sex-specific patterns, and as a result of this, adolescence has historically been viewed as a period of vulnerability. A wide array of neuroanatomical maturation occurs during adolescence as well, suggesting that the adolescent cortex is increasingly plastic. One of the most notable of these changes is the development of the prefrontal cortex (PFC), a brain region involved in higher-order cognition and mediating social behaviors. Neuronal changes that occur in this region during adolescence may underlie the cognitive, social, and emotional development that occurs at this time Though it is difficult to define an exact age range that encompasses adolescence, one hallmark of this developmental stage is puberty. A common event among mammalian species, pubertal onset is defined by a rise in gonadal hormones that culminates in sexual maturity. Evidence shows that these hormones can also act on neuronal circuits, ultimately shaping various behaviors. Some evidence from humans indicates that gonadal hormones correlate with the maturation of the PFC and PFC-mediated behaviors. However, assessing and controlling for pubertal onset in human subjects is difficult, necessitating rodent models to understand the role of puberty in the development of the adolescent cortex. Therefore, this dissertation aims to further elucidate the role of puberty on behaviors and the neuroanatomical structure of the mPFC in a rodent model of adolescence. Chapter 2 focuses on behavioral changes that coincide with pubertal onset, specifically examining spatial learning, cognitive flexibility, and anxiety-like behaviors in male and female rats. Using a modified Morris water maze task, we show that males and females experience rapid increases in mPFC-dependent cognitive flexibility capabilities, reaching adult-like levels within days after pubertal onset. These changes occur in the absence of any improvement on the spatial learning task, suggesting that gonadal hormones act on the mPFC during this time. Interestingly, we see a similar developmental pattern of behavior only in females on the elevated plus maze, where recently post-pubertal females behave like adults in terms of open arm time and entries. Together, these studies suggest that gonadal hormones can act quickly to organize the mPFC during adolescence and induce adult-like behaviors on mPFC-mediated tasks, sometimes in sex-specific patterns. Chapters 3, 5 and 6 examine neuroanatomical development of the rodent mPFC and how these variables change at the pubertal onset. First, we quantify the total number of synapses in the mPFC across the juvenile period and into adulthood and present evidence that both males and females undergo synaptic pruning that coincides with pubertal onset. Next, studying similar ages, we examine the ontogeny of the total number of mPFC perineuronal nets (PNNs), which are important mediators of cortical plasticity and synaptic stability. This study describes that these structures remain juvenile-like in males and females across adolescence, suggesting the cortex continues to be plastic at this time. Interestingly, PNNs are significantly downregulated in females post-pubertally, suggesting that estrogen can influence PNN structure. We then quantify expression of Esr2, the gene that encodes for the estrogen receptor β, in pre- and recently post-pubertal females using RNAScope, and note that Esr2 is significantly decreased in the post-pubertal subjects. A decrease in this receptor could have implications for adolescent behaviors that are influenced by estrogens, such as fear extinction or cognitive behaviors. Finally, we provide evidence in Chapter 4 that the developmental events occurring at pubertal onset may render adolescents susceptible to the effects of stress, as previous human and animal literature suggests that developing brain regions are more vulnerable to the effects of the environment. This study exposes male and female rats to a stressor either peri- or post-pubertally and finds that only those stressed peri-pubertally showed long-term behavioral deficits on a prepulse inhibition task. These results provide further evidence that pubertal onset is driving many of the behavioral and neuroanatomical changes seen during adolescence, suggesting a specific window during adolescence where the effects of experience are most impactful. Together, the findings presented in this dissertation add to the body of literature that shows the frontal cortex continues to mature during adolescence. We demonstrate here that many, but not all, of these maturational events occur in rodents on a non-linear time scale and coincide with pubertal onset. Here, we argue that future researchers should be aware of these developmental changes that occur when studying adolescents, and control for pubertal onset whenever possible. Finally, these results have implications for researchers who study adolescent vulnerability and highlight that pubertal hormones could be an important mediating factor in this work.
Issue Date:2021-01-29
Type:Thesis
URI:http://hdl.handle.net/2142/110410
Rights Information:Copyright 2021 Carly Drzewiecki
Date Available in IDEALS:2021-09-17
Date Deposited:2021-05


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