Effects of third trimester alcohol exposure on vicarious trial and error behaviors and mPFC-HPC oscillatory synchrony during spatial working memory in adulthood
Date
2024
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Publisher
University of Delaware
Abstract
Alcohol exposure during pregnancy is known to result in a range of physical, cognitive, and behavioral impairments, together known as Fetal Alcohol Spectrum Disorders (FASD). Exposure during the brain growth spurt, which occurs during the third trimester in humans and postnatally in rodents, damages the medial prefrontal cortex (mPFC), hippocampus (HPC), and thalamic nucleus reuniens (Re). mPFC-HPC theta synchrony via Re is important for spatial working memory. Regions in the mPFC-Re-HPC circuit have additionally been implicated in deliberative behaviors known as vicarious trial and errors (VTEs), which are associated with learning and adapting to changes in task demands. ☐ We predicted that alcohol exposure during the brain growth spurt would impair spatial working memory, alter VTE behaviors, and disrupt mPFC-HPC oscillatory synchrony during decision-making. To study these effects, rats were either exposed to alcohol during postnatal days 4-9 or were sham intubated. During adulthood, rats were tested on the delayed alternation spatial working memory task while video tracking data and local field potentials from the mPFC and HPC were recorded. ☐ Contrary to our prediction, spatial working memory was not impaired in the alcohol exposed group. However, we observed behavioral differences related to VTEs, as the proportion of trials with VTEs was lower in the alcohol exposed group compared to the sham intubated group and the relationship between VTEs and task experience was disrupted. Specifically, whereas sham intubated rats showed a decrease in the proportion of trials with VTEs over sessions, alcohol exposed rats showed no change in VTE proportion. We also observed that the relationship between VTEs and flexible decision-making was altered in our alcohol exposed rats, as they showed a positive correlation between the proportion of VTEs and the proportion of inflexible repeated choice error sequences, known as perseverative errors, during task performance. Analysis of the neural data revealed that the alcohol exposed group showed altered mPFC and HPC power spectral density and mPFC-HPC coherence compared to the sham intubated group. Overall, this study demonstrates that alcohol exposure affects mPFC-HPC oscillatory synchrony and deliberative behavior in adulthood, leading to a better understanding of the impairments seen in humans with FASD.
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Keywords
Fetal Alcohol Spectrum Disorders, Hippocampus, Local field potentials, Medial prefrontal cortex, Spatial working memory, Behavioral impairments