Model of Fetal Alcohol Spectrum Disorder

Fetal Alcohol Spectrum Disorder (FASD) is an umbrella term used to describe the range of outcomes that result from prenatal exposure to alcohol (ethanol). Behavioral effects may include hyperactivity, attention deficit, impaired sensory processing, and learning and memory problems. People with FASD may also have difficulties using information flexibly which likely underlies deficits in cognition. Such problems are thought to be seated in frontal cortices, including prefrontal cortex. Devising new strategies for amelioration of these problems has great clinical relevance. While deficits in learning and memory have been extensively demonstrated in rodent models of FASD, we will examine cognitive flexibility. We propose an innovative experimental design in which rats exposed to a moderate dose of ethanol prenatally are given choline AND behavioral training during adolescence. Either alone can improve learning and memory in normal animals, as well as in models of FASD. We have chosen the attentional set shifting and reversal learning task because it captures deficits reported in clinical observation of individuals with FASD and also because it can be used repeatedly in the same rats without observable diminution of responding or changes in task strategy. We propose a multidisciplinary set of experiments that will assess behavior, brain function and structure, as well as expression of neurometabolites. These experiments will determine whether modulating plasticity during frontal cortex development can improve both memory and problem solving in the same animals and how the effects manifest in brain connectivity and structure.