Not all is lost; prenatal ethanol exposure impairs bidirectional synaptic plasticity in the juvenile dentate gyrus
Date
2018-12-20
Authors
Fontaine, Christine Jessie
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Abstract
Fetal alcohol spectrum disorders (FASDs) are among the leading preventable disorders in North America and are caused by prenatal ethanol exposure (PNEE). Ethanol is a teratogen, and prenatal exposure leads to structural and functional impairments that depend on the amount, timing and duration of exposure. PNEE is commonly associated with learning and memory impairments, which are paralleled by deficits in synaptic plasticity. A number of studies have shown deficits in long-term potentiation (LTP) of synaptic plasticity in the hippocampus, however, to date few studies have determined how PNEE impacts long-term depression (LTD). Here, we examine the effect of PNEE on the dynamic range of synaptic plasticity, by studying both LTP and LTD in the juvenile Dentate Gyrus (DG) of male and female offspring. We find that PNEE impairs N-methyl-D-aspartate receptor (NMDAR)-dependent LTP in both sexes. This appears to be the result of a change in the threshold for induction, as increasing the amount of stimuli administered can restore the LTP to control levels. We found that LTD was significantly reduced in male, but not female, offspring following PNEE. As with LTP, these deficits could be rescued by increasing the stimulation used to elicit synaptic depression. Unlike LTP, which was NMDAR dependent, LTD induction required the activation of both metabotropic glutamate 5 receptors (mGluR5) and cannabinoid type 1 (CB1) receptors. These data are the first to describe the impact of PNEE on the dynamic range of synaptic plasticity in the DG of juvenile male and female offspring. The findings in this dissertation further describe the potential mechanistic underpinnings of learning and memory deficits, and help identify new therapeutic targets to examine for enhancing hippocampal function in young people afflicted with FASD.
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Teratogen, Synaptic Plasticity, Hippocampus, Fetal Alcohol Spectrum Disorders, Sex Differences, Juvenile