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Title: Investigating the Role of Perineuronal Nets in the Effects of Early Life Adversity on Avoidance Behavior
Authors: Bodnar, Saoirse
Advisors: Gould, Elizabeth
Department: Neuroscience
Certificate Program: Global Health and Health Policy Program
Class Year: 2022
Abstract: People exposed to early life adversity (ELA), including neglect, abuse, or parental separation, have an increased risk for developing persisting psychiatric problems, including anxiety, depression, and posttraumatic stress disorder (PTSD). In addition, ELA has been associated with persistent behavioral and neurobiological changes throughout the brain, including in the hippocampus. Attempting to understand the various maladaptive consequences of ELA in humans has led researchers to mimic the effects in animal models of ELA. Previous research has highlighted that the maternal separation/early weaning (MSEW) model has been shown to induce consistent, long-lasting avoidance behavior and increase the intensity of perineuronal nets (PNNs), specialized extracellular matrix structures linked to plasticity,in the ventral hippocampus, a region in the rodent brain linked to avoidance or “anxiety-like” behavior. Reducing PNNs around PV cells in adult rodents has been shown to reopen plasticity in other systems by resetting inhibitory circuits to a juvenile state. This study aimed to determine whether avoidance behavior is reduced in mice with diminished PNNs in the ventral hippocampus. After MSEW or control rearing, we used bilateral injections of chABC to degrade the PNNs in the ventral hippocampus of adults and then allowed PNNs to partially regrow to determine whether adult mice subjected to MSEW with lowered PNN intensities exhibit reduced levels of avoidant behavior. We then categorized mouse behavior on an EPM and distinguished between two- and four- paw entries into each arm as measures of exploratory behavior (two- paw entries imply higher levels of exploration). We found that MSEW resulted in significant reductions in exploratory behavior, but that these reductions are reversed by bilateral injections of chABC into the ventral hippocampus. Changes in MSEW were documented in some measurements, but not others. This investigation extends existing literature by confirming our hypothesis that PNN reduction restores exploratory behavior and provides the motivation for future investigations into the implications of PNN reduction in experiments with MSEW mice. Ultimately, this research hopes to offer hints for future clinical investigations aimed toward improving existing and developing new therapeutic interventions for people that experience ELA. In the mean time, the parallels between this investigation and the human effects of ELA encourage us institute public health policies to avoid parental separation to hopefully mitigate some of the effects of ELA.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Neuroscience, 2017-2022
Global Health and Health Policy Program, 2017-2022

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