Skip navigation
Please use this identifier to cite or link to this item: http://arks.princeton.edu/ark:/88435/dsp01gq67jv577
Title: EARLY LIFE ADVERSITY AND HIPPOCAMPAL PLASTICITY: EXPLORING GENETIC, SEX, AND EXPERIENCE-DEPENDENT VARIATION
Authors: Waters, Renee Chanel
Advisors: Gould, Elizabeth
Contributors: Psychology Department
Keywords: adult neurogenesis
early life adversity
hippocampus
perineuronal nets
Subjects: Neurosciences
Issue Date: 2024
Publisher: Princeton, NJ : Princeton University
Abstract: Early life adversity (ELA) is a predisposing factor for several neuropsychiatric diseases. Specifictypes of ELA are known to produce differing vulnerabilities to certain conditions. This thesis focuses on ELA-induced behavioral dysfunction in avoidance behavior and social discrimination function, both of which are key characteristics in some neuropsychiatric diseases. The goal of this thesis is to identify and target underlying mechanisms for therapeutic intervention in adulthood. Chapter 1 takes a broad look at the human literature surrounding early life adversity and its connection to adult neuropsychiatric diseases to understand the variation that exists in neuropsychiatric diagnoses. In subsequent chapters, mouse models that likely reflect two broad types of ELA in humans—neglect and resource scarcity—were used to investigate the effects of different types of ELA. Avoidance behavior has been shown to characteristically increase after ELA experiences in humans and rodents. Chapter 2 examines avoidance behavior after neglect using MSEW (Maternal Separation with Early Weaning) and the role of adult neurogenesis, the addition of new neurons to the adult brain, in the hippocampus. Contrary to previous studies, the neglect model (MSEW) did not produce any behavioral changes in male mice. However, reducing adult-born granule cells (abGCs) produced a decrease in avoidance behavior, indicating a potential role of abGCs in avoidance behavior. In Chapter 3, the two ELA models were directly compared in a social behavioral task and neural mechanisms were investigated. The neglect model produced a deficit in social recognition that lasted into adulthood in males, but not females. Consistent with the hypothesis that abGCs are required for social memory, male mice who experienced MSEW produced fewer stem cells, fewer abGCs, and abGCs had fewer connections within the hippocampus. Using a double transgenic approach to increase the activation of the remaining new neurons in ELA-neglect mice was sufficient to restore social recognition abilities. Additionally, increasing the number of abGCs using environmental enrichment was also sufficient to restore social recognition abilities. Lastly, for the neglect model (MSEW), in vivo recordings of the hippocampus established electrophysiological signatures for ELA-induced impairment and restoration of function. The model of scare resources (Limited Bedding and Nesting; LBN) produced a deficit in social novelty preference in adulthood in males, but not females. Unlike the model of neglect, the model of scarce resources did not alter adult neurogenesis but instead increased the expression of specialized extracellular matrix structures known to inhibit plasticity, called perineuronal nets (PNNs), in the hippocampus. Targeted disruption of hippocampal PNNs in LBN mice successfully restored social novelty preference and social discrimination function. Future studies will investigate electrophysiological network differences between control and LBN mice and whether these differences are restored by PNN degradation. Taken together, these findings suggest that ELA-induced outcomes are dependent on both genetic and experiential factors.
URI: http://arks.princeton.edu/ark:/88435/dsp01gq67jv577
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Psychology

Files in This Item:
This content is embargoed until 2025-10-01. For questions about theses and dissertations, please contact the Mudd Manuscript Library. For questions about research datasets, as well as other inquiries, please contact the DataSpace curators.


Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.