Grant: Master's Award: Canada Graduate Scholarships

Consuming alcohol during pregnancy causes a range of lifelong effects on the offspring, known as Fetal Alcohol Spectrum Disorders (FASD). Recent research has explored supplementing the essential nutrient choline to mitigate the associated cognitive deficits. These studies have seen promising results when measuring behavioural outcomes in both animal studies of prenatal ethanol exposure (PNEE) and in clinical trials. However, little is understood of the mechanisms behind this treatment. This study will use a rodent model of FASD to elucidate changes within the hippocampus, an area of the brain vital to memory consolidation. Memories are formed from the strengthening of neuronal synapses, a process known as long term potentiation (LTP). LTP is modulated by cholinergic inputs, acetylcholine producing neurons, and alteration of these circuits may be one mechanism in which choline rescues cognitive impairments. Offspring will be exposed to ethanol throughout the gestational period, with 35.5% of the caloric intake derived from ethanol. Choline treatment will begin on postnatal day 10. Hippocampal-dependent behavioural tasks will validate that choline rescues memory deficits in this model of PNEE. Electrophysiological recordings in the dentate gyrus of the hippocampus will elucidate changes on a molecular level, specifically to determine if choline enhances LTP in PNEE animals. Additionally, pharmaceutical agents that block cholinergic receptors or stimulate their activity will confirm that the modulation of LTP is dependent on local changes in choline activity. Together, these experiments will further define the mechanisms behind postnatal choline supplementation and provide molecular evidence for the rescuing of cognitive impairments in this potential treatment of FASD.