Nora is a sixth year PhD candidate in Michael Goard’s lab in the Molecular, Cellular, and Developmental Biology PhD program. She was born and raised in Buffalo, New York, where she fostered a love for science. In 2015 she moved to Washington, DC, where she received a BS in Cellular and Molecular Biology and a BA in Music Performance from the George Washington University. While in Washington, DC she initially studied the genetic underpinnings of body patterning in butterflies and later worked at the National Institutes of Health interrogating the neural circuitry of feeding behavior. Her current work focuses on investigating the neural circuits underlying sex differences in hippocampus. In pursuit of her thesis work she has developed technologies for longitudinal two-photon imaging in mice, as well as automated classification of murine hormonal state. She is currently supported by an NINDS F99 BRAIN Institute fellowship. While not in lab, Nora enjoys hiking, reading, and spotting new birds.
Abstract: Chronic Recording of Hippocampus across Pregnancy and Postpartum Reveals Long-term Structural Changes
Authors: Nora Wolcott [1], Lindsey Washiashi [1], Ariella Zulch [1], Emily Jacobs [1], Michael Goard [1].
[1] University of California, Santa Barbara
Pregnancy is a period of profound hormonal and physiological change that has been shown to cause widespread alterations in brain structure and function. Despite this, the underlying neuronal mechanisms driving these changes remain poorly understood. In particular, it is unclear how neuronal morphology contributes to pregnancy-related shifts in brain volume and to what extent these changes persist beyond parturition. To address this, we developed a novel noninvasive liquid chromatography-mass spectrometry (LC-MS) approach to quantify estradiol, progesterone, and corticosterone levels throughout pregnancy and postpartum in mice. We then performed longitudinal two-photon structural imaging using a custom-implanted glass microperiscope targeting the dorsal hippocampus. This approach enabled repeated measurements of dendritic spine density and branch morphology across several months. We observed an unprecedented 31% +/- 2% increase in spine density during pregnancy, followed by an 38% +/- 5% decline at parturition. Notably, 15 weeks postpartum spine density stabilized at 7% +/- 2% relative to baseline, a sustained increase from pre-pregnancy, suggesting long-term remodeling of hippocampal circuits. These structural changes were strongly correlated with circulating estradiol concentration, consistent with the well-established role of estrogen in hippocampal spinogenesis. In future work, we will use a miniaturized two-photon microscope to measure the functional activity of these neurons during foraging behavior across pregnancy and postpartum. Additionally, we will employ localized ERα and ERβ receptor knockdowns in the hippocampus to determine the extent to which estrogenic signaling mediates these structural and functional changes. Together, these findings are the first to longitudinally demonstrate that pregnancy induces lasting modifications to synaptic connectivity, a finding of major clinical relevance to the millions of women who experience pregnancy annually. Funding: This work was supported by the NSF (M.J.G., NeuroNex #1707287), the NIH (M.J.G., R01NS121919, N.S.W. F99NS139514), the Whitehall Foundation (M.J.G.), and the Larry Hillblom Foundation (M.J.G.).