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James L. McGaugh Distinguished Seminar Series
Tuesday, April 25, 2023 at 11:00am
The seminar will be live streamed via Zoom and In-Person.
Elizabeth Gould, PhD
Department of Psychology
Princeton Neuroscience Institute
“Sex differences in early life adversity effects on hippocampal plasticity”
Abstract: Early life adversity (ELA) increases the likelihood of neuropsychiatric disease, including anxiety and mood disorders. Sex differences exist in the incidence of these conditions, and types of ELA are known to produce differential vulnerabilities. My talk will focus on our efforts to use two different mouse models of ELA to explore plasticity mechanisms underlying sex differences in behavioral outcomes. We found that an ELA model of neglect, but not one of abuse, increases ventral hippocampal-dependent avoidance behavior in both males and females. Overall, females exhibit greater avoidance than males, with further increases observed after ELA only during the diestrus phase of the estrous cycle. Increases in avoidance in ELA females during diestrus are likely related to diminished conversion of progesterone to the neurosteroid allopregnanolone in the ventral hippocampus. These changes are coincident with increased power of theta oscillations and altered composition of perineuronal nets, extracellular matrix structures known to limit plasticity, around parvalbumin-positive inhibitory interneurons. Sex differences are also observed in response to two types of ELA on social recognition, another function that involves the hippocampus. Males, but not females, show deficits in social memory after exposure to ELA models of neglect or abuse. Despite these similarities within males, underlying mechanisms differ depending on the type of ELA experienced. ELA-neglect reduced the number of stem cells and adult-born neurons in the hippocampus. This effect seems causally linked to social recognition deficits because chemogenetic stimulation of adult-born neurons in ELA-neglect mice restores this function. By contrast, ELA-abuse does not affect the number of adult-born neurons but increases perineuronal nets in the CA2 region. Collectively, these findings highlight how sex and ELA type are important determinants of hippocampal plasticity and behavioral outcomes.
Profile Link: https://gouldlab.princeton.edu/