Long-term effects of fetal alcohol spectrum disorders on dentate gyrus synaptic plasticity




Helfer, Jennifer Lauren

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Developmental ethanol exposure causes both structural and functional changes in the brain that can result in cognitive and behavioral abnormalities. The hippocampal formation, an area of the brain strongly linked with learning and memory, is particularly vulnerable to the teratogenic effects of ethanol. Research in this thesis focused on uncovering the effects of developmental ethanol exposure on hippocampal function in adulthood, particularly synaptic plasticity (a putative neurobiological mechanism of learning and memory). The first experiment sought to determine the temporal vulnerability of hippocampal synaptic plasticity as a function of exposure to ethanol during a single trimester. Ethanol exposure during the 1st or 3rd trimester equivalent resulted in minor changes in synaptic plasticity in adult offspring. In contrast, ethanol exposure during the 2nd trimester equivalent resulted in a pronounced decrease in long-term potentiation (LTP), indicating that the timing of exposure determines the severity of the deficit. The second experiment was aimed at determining the effects of prenatal ethanol exposure (1st and 2nd trimester equivalent combined) on bidirectional synaptic plasticity. Prenatal ethanol exposure resulted in a profound reduction in LTP but did not affect long-term depression. These findings show that prenatal ethanol exposure creates an imbalance in bidirectional synaptic plasticity. The third experiment sought to determine if prenatal ethanol exposure alters the affect of acute ethanol exposure in adulthood on synaptic plasticity. Acute exposure to ethanol in adulthood attenuated LTP in control offspring. Conversely, the magnitude of LTP was not affected by acute ethanol application in prenatal ethanol offspring. These results suggest that prenatal ethanol exposure alters the physiological response to ethanol in adulthood. Together, the results from the experiments undertaken in this thesis demonstrate long-lasting alterations in synaptic plasticity as the result of developmental ethanol exposure. Furthermore, these results allude to a malfunction of neural circuits within the hippocampal formation, perhaps relating to the learning and memory deficits observed in individuals with fetal alcohol spectrum disorders.



Fetal Alcohol Spectrum Disorders, ethanol, plasticity, dentate gyrus