Medial prefrontal cortex and hippocampus oscillatory synchrony and behavioral disruption in a rat model of fetal alcohol spectrum disorders: evidence from in vivo electrophysiology
Date
2025
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Publisher
University of Delaware
Abstract
Children diagnosed with Fetal Alcohol Spectrum Disorders (FASD) are more likely than their peers to show deficits in executive function, learning, and memory. In rodent models of FASD, brain regions including the hippocampus (HPC), medial prefrontal cortex (mPFC), and midline thalamic nucleus reuniens (RE) have been shown to be particularly vulnerable to ethanol effects during the brain growth spurt, which occurs during the third trimester in humans and the first two postnatal weeks in rats. This damage could disrupt functional interactions between these regions that support working memory, the ability to maintain and flexibly update task-relevant information. Previous studies from our lab showed that RE is critical for spatial working memory and mPFC–HPC functional interactions. We also have demonstrated that RE was significantly damaged in a rat model of binge drinking during the third trimester. Based on these findings, we hypothesized that alcohol exposure (AE) during the brain growth spurt could impair working memory and mPFC – HPC oscillatory synchrony. For all experiments, male and female rat pups were assigned either to the AE group, in which pups were given daily doses of 5.25 g/kg of alcohol in a binge manner via intragastric intubation on postnatal day (PD) 4-9, or to a sham intubated (SI) control group. Starting at PD90, rats were tested on a spatial alternation task with 10s, 30s, and 60s delay trials interleaved within a testing session. For in vivo electrophysiology experiments, local field potentials were recorded from prelimbic cortex of mPFC and dorsal CA1 as rats performed a spatial alternation task. The studies in this dissertation are guided by three specific aims: Specific Aim 1 addressed long-term effects of developmental AE on spatial working memory in adulthood. Results demonstrated that AE did not impair spatial working memory, however, we observed that AE did impact behaviors other than working memory. Specific Aim 2 examined the correlation between RE neuroanatomical integrity and spatial working memory performance from Aim 1. Specific Aim 3 investigated how developmental AE affects functional connectivity between mPFC and HPC during spatial working memory task performance. Results revealed alterations in mPFC and HPC power across all frequency bands of interest: theta (6-10Hz), mid-beta (15-20Hz), and gamma (30-50Hz) frequency bands. Additionally, Aim 3 demonstrated that there were significant alterations in mPFC – HPC functional connectivity across those bands. Specifically, early postnatal AE reduced coherence in theta frequency (6 -10 Hz) band but increased coherence in the mid beta (15 – 20 Hz) and gamma frequency (30 – 50 Hz) bands. These findings suggest that the previously established AE-related damage to brain structures incurred during the brain growth spurt results in abnormalities in behavior, HPC and mPFC physiology, and mPFC – HPC functional connectivity.
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Keywords
Fetal Alcohol Spectrum Disorders, Functional connectivity, Hippocampus, Spatial working memory, Theta coherence