Ethanol exposure during neurodevelopment can have long- term adverse effects on brain function, resulting in defects in memory and a high risk for major psychiatric disorders. The mechanisms underlying the changes in neuropsychiatric function are poorly understood but thought to result from effects on synaptic transmission. Recently, Olney and colleagues provided important information about the effects of ethanol on the developing central nervous system (CNS). These investigators found that treatment of early postnatal rats with intoxicating doses of ethanol over a single four hour period results in massive apoptotic neurodegeneration in many regions of the CNS, including the hippocampus. Because the hippocampus plays a key role in memory processing, it is likely that early damage to this structure influences longer-term memory function. In this proposal, we will examine the consequences of early postnatal ethanol exposure on synaptic function and plasticity using in vitro hippocampal slices prepared from adolescent and young adult rats exposed to ethanol at ages associated with augmented hippocampal apoptosis.
The specific aims of this project are: 1. To determine the effects of early postnatal ethanol exposure on basal synaptic transmission, synaptic responses mediated by N- methyl-D-aspartate glutamate receptors (NMDARs) and the threshold for induction of NMDAR-dependent long-term potentiation (LTP) and long-term synaptic depression (LTD) in the CA1 region of hippocampal slices. For these studies we will use slices prepared from postnatal day 35 (P35) and P180 rats. 2. To determine how changes in hippocampal morphology and plasticity translate into changes in hippocampal-dependent forms of learning and memory in adolescent (P35) and adult (P180) rats exposed to ethanol early in postnatal development. These studies will build on preliminary data indicating that early ethanol exposure results in significant changes in the ability to induce homosynaptic LTD in the CA1 hippocampal region. It is hoped that better understanding of how early postnatal ethanol exposure alters hippocampal function will lead to more effective treatments for individuals with disorders resulting from fetal alcohol exposure.
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