The development of cerebral cortex is profoundly disrupted by the prenatal exposure to ethanol. These defects provide the basis for a variety of disorders including mental retardation and motor dysfunction which characterize fetal alcohol syndrome (FAS). The initial two years of this project were devoted to surveying the effects of prenatal ethanol exposure on neuronal ontogeny. This proposal outlines a more detailed examination of the effects of prenatal exposure to ethanol on the ontogeny of neurons and glia in motor-somatosensory cortex. Three processes constitute cellular ontogeny; proliferation, migration, and differentiation. The effects of prenatal exposure to ethanol on each of these phases will be examined. The proliferation of cortical neurons and glia will be assessed using double-labeling immunocytochemical and autoradiographic techniques which makes it possible to trace the """"""""life history"""""""" of morphologically identified neurons. These studies are intended to examine the effects of ethanol upon intrinsic (cell cycle) and extrinsic (circadian rhythms) components of neurogenesis and gliogenesis. Cellular migration depends upon complex neuronal- glial interactions. The effects of ethanol on various factors controlling migration, e.g., the physical glial support, chemical cues such as glycoproteins and lectins in the extracellular matrix and cell adhesion molecules, and conduits for electrotonic communications, will be examined. Earlier studies have been shown that neuronal differentiation is affected by prenatal exposure to ethanol. The effects of prenatal exposure to ethanol on the arrival and synaptogenesis of monoaminergic and cholinergic """"""""non-specific"""""""" afferents, thalamic and callosal """"""""specific"""""""" afferents, and efferents in the pyramidal tract will be examined. The morpho-physiological nature of corticospinal neurons, the neurotransmitters of local circuit neurons, and the glucose utilization of projection neurons, local circuit neurons, and glia will be studied. These studies will examine the mechanisms, rather than the phenomenology of the teratological effects of ethanol. Knowledge of these mechanisms will provide insights to possible preventatives for FAS.
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