When consumed during gestation, ethanol produces acute affects upon fetus. Moreover, fetal alcohol exposure produces teratological effects ranging in severity from gross dysmorphias and profound mental retardation to subtle disturbances of behavior and cognition. Mental retardation and learning disabilities are perhaps the most frequently reported and devasting of these effects. Even at levels of exposure which produce no overt dysmorphias, cognitive deficits are manifested which profoundly compromise the function of the individual. The hippocampus is involved in the process of learning and memory and is also quite susceptible to neurotoxic and teratological insult. In particular, hippocampal cells are damaged by chronic adult exposure to alcohol, and moreover by in-utero exposure despite complete postnatal, abstinence. A functional deficit in the hippocampi of animals exposed prenatally to ethanol has been suggested by studies showing slower rates of kindling and decreased glutamate binding relative to controls. However, as yet no physiological demonstration of such a deficit has been uncovered. Our pilot data point to such a demonstration. Studies using hippocampal slices from rats prenatally exposed to ethanol, have yielded preliminary evidence that the pyramidal cells of area CA3 are less easily synchronized into burst firing patterns than are those from controls. Moveover, CA1 pyramidal cells from exposed animals manifest less long-term potentiation (LTP) than do those from controls. These results, particularly the LTP studies, may reflect the underpinnings of the learning deficits associated with fetal ethanol exposure, and maybe specifically related to the previously-reported decreases in hippocampal glutamate binding. In this proposal we will assess the functional integrity of the hippocampus after prenatal exposure to ethanol. Using electrophysiological techniques, we will examine the responsiveness of pyramidal cells to certain amino acid agonists, assess the rate at which hippocampal circuits can be stimulated electrically into a hyperexcitable state, and determine the degree to which the circuits of the hippocampus can facilitate LTP. This latter process will be correlated with passive avoidance learning. Our goals are 1) to demonstrate and describe the functional impact of prenatal ethanol exposure on the hippocampal formation, and 2) to develop a model system in which to study these effects.
