Moderate doses of alcohol and the developing cerebellum

University Of Vermont &St Agric College, Burlington VT

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Abstract

DESCRIPTION (provided by applicant): The long-term objective of this research is to determine the patterns of alcohol consumption during pregnancy that results in long-term damage to the cerebellum. While it is well established that doses of alcohol that produce high blood alcohol concentrations ("binge-like exposure") over a limited portion (postnatal days 4-9) of the human third trimester-equivalent in rats can permanently damage the cerebellum, much less is known about the effects of producing lower blood alcohol concentrations over a more extended period of development. The impact on the cerebellum can be studied by combining eye blink classical conditioning, a cerebellar-dependent task that engages a well-studied and fully delineated cerebellar circuit, with counting of cerebellar cells and recording of neuronal activity in defined areas of the cerebellum. The specific aims of the proposed research are to combine these behavioral, neuroanatomical, and neurophysiological techniques to examine the impact on the adult cerebellum of acute, low dose exposure to alcohol during a longer period of the third trimester than is usually examined. Two experiments are proposed. In Experiment 1, rats will be exposed to a low dose of alcohol once per day across postnatal days 2-11. As adults they will be tested on eyeblink conditioning and cell counts of two cerebellar cell populations critical for learning, interpositus nucleus cells and Purkinje cells, will be made and compared to behavioral performance. In Experiment 2, the same neonatal treatments will be performed and, as adults, rats will be tested on eyeblink conditioning while neuronal activity from the interpositus nucleus is recorded. When completed, these results will provide important evidence regarding the extent to which moderate consumption of alcohol across an extended period of the third trimester impacts the developing cerebellum and will help to determine which alcohol consumption patterns over what time period of development damage the cerebellum. This knowledge is important for developing effective interventions and therapies for children exposed to alcohol prenatally.