Dietary supplementation of choline during gestation in the rat results in memory enhancement during adulthood. In the case of prenatal choline supplementation this memory enhancement is accompanied by increased ACh release and decreased AchE activity, increased levels of nerve growth factor (NGF), and increased phospholipase D (PLD) activity in the hippocampus. These fundings suggest that prenatal choline supplementation may result in a permanent change in hippocampal organization and/or neurochemistry resulting in a bias towards excitation and synaptic plasticity with intr-hippocampal circuits. Recent studies have also shown the prenatal supplementation with folate results in memory enhancements which are similar to those observed after prenatal choline supplementation. Given the known biochemical interdependencies between dietary methyl group donors such as folate and choline, it is possible that the behavioral effects of prenatal manipulations of these compounds may share common neurophysiological mechanisms. During the past year we have shown the both prenatal and perinatal choline supplementation cause an apparent lowering of the threshold for the induction of LTP in area CA1 of hippocampal slices taken from young adult rats. Conversely, in those studies prenatal choline deficiency resulted in an apparent elevation of LTP threshold. Therefore, we hypothesize that perinatal choline deficiency will compromise excitatory synaptic activity and the induction of LTP in these structures. We will first assess LTP in area CA1 and the dentate gyrus in slices from control, choline supplemented, choline deficient, folate supplemented, or folate deficient rats at three to four months of age. All dietary treatments will occur during gestation days 12-17 only. Separate experiments will assess LTP induced by electrical stimulus trains or carbachol exposure. In addition, we will assess NMDA receptor-dependency of the electrically induced LTP, and the input/output relationships of NMDA receptor/mediated synaptic responses. To assess the age-dependency of these electrophysiological sequelae of perinatal choline exposure, the second set of experiments will evaluate LTP threshold, magnitude, and duration in slices from animals form each of the treatment groups at approximately two years of age. Our final set of experiments will assess hippocampal LTP in- vivo in rats from each of the treatment groups. These experiments will provide a framework for interpreting the in-vitro findings. These studies will provide an electrophysiological characterization of hippocampal circuits from animals with a history of perinatal choline and folate manipulations, and an assessment of the types and mechanisms of synaptic plasticity in the hippocampi of these animals.
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