Fetal Alcohol Syndrome may be one of the most common types of mental retardation having an identified etiology, with affected children demonstrating decreased brain size and brain malformations. These gross abnormalities are probably indicative of serious errors occurring at the cellular level of brain development. We propose to examine Fetal Alcohol Syndrome in a central nervous system structure associated with learning and memory, the hippocampal formation, which may be implicated in some of the reported nervous system deficits. The hippocampal formation has been an important model system for the study of development, structure-function and plasticity in the central nervous system. Also, the hippocampus has been shown to be highly sensitive to the toxic effects of alcohol in developing and adult animals. We will test and hypothesis which states that fetal alcohol exposure will cause differential teratogenic effects in the wiring and responsiveness of neuronal circuitry within the hippocampal formation of the male and female offspring. Using time course studies, we will examine the effects of fetal alcohol exposure on: (I) synaptogenesis in the male and female hippocampus by quantitative electron microscopy, (II) the laminar distribution of the major afferent inputs to the hippocampus (dentate gyrus) by quantitative light microscopic histochemistry and autoradiography and (III) lesion-induced neuronal plasticity in the dentate gyrus of 30 day old male and female animals by quantitative electron microscopy. Completion of the specific aims of the proposed study will provide a detailed morphological description of the teratogenic effects of fetal alcohol exposure in a central nervous system area very likely to be involved in the behavioral symptoms observed in Fetal Alcohol Syndrome children, and we may better understand the effects and mechanisms involved in this commonly occurring disease.
