|
Verginia Cuzon, Graduate Student
Abuse of ethanol during pregnancy can be detrimental to the offspring, the most severe detriment being the developmental defects collectively referred to as fetal alcohol syndrome (FAS), and hallmarked by defects in gross brain morphology (e.g., microcephaly, hydrocephaly, porencephaly, hydroanencephaly), all of which have been attributed to insult during corticogenesis. Prenatal chronic ethanol exposure compromises the GABAergic system in the immature brain and, thus, contributes to increased susceptibility to seizures and deficits in sensory information processing often associated with FAS. In this project, we ask whether chronic ethanol consumption during pregnancy leads to abnormal development of the GABAergic system in the offspring. The overriding hypothesis is that the abnormal disposition of the postnatal and mature cortex seen in FAS manifests itself early on in corticogenesis by affecting the migration of primordial GABAergic interneurons to their usual laminar positions within the neocortex. In rodent, these GABAergic interneurons arise extracortically primarily from the medial ganglionic eminence (MGE) and migrate tangentially into the developing neocortex. In testing our hypothesis, we hope to answer the following questions: (1) Does prenatal ethanol exposure in utero disrupt the tangential migration of MGE-derived cells in a dose and time dependent manner? (2) Are the observed changes in tangential migration of MGE-derived cells the result of a direct interaction between ethanol and the GABAergic system? (3) If so, does chronic ethanol exposure in utero cause changes in GABAA receptors of MGE-derived cells or in GABA release mechanisms? This project will for the first time define the effect of ethanol consumption during early stages of pregnancy on the embryonic development of a specific and important population of cells in the neocortex, notably the GABAergic cortical interneurons. In the long run, the proposed studies will lay the groundwork for assessing how disruptions of the cortical neuronal circuitry underlie many of the behavioral abnormalities seen in FAS.