We tested the hypothesis that excess saturated fat consumption during pregnancy, lactation and/or post-weaning alters the expression of genes mediating hippocampal synaptic efficacy and impairs spatial learning and memory in adulthood. Dams were fed control chow or a diet high in saturated fat before mating, during pregnancy and into lactation. Offspring were weaned to either standard chow or a diet high in saturated fat. Morris Water Maze was used to evaluate spatial learning and memory. Open field testing was used to evaluate motor activity. Hippocampal gene expression in adult males was measured using RT-PCR and ELISA. Offspring from high-fat fed dams took longer, swam farther and faster to try and find the hidden platform during the five day learning period. Control offspring consuming standard chow spent the most time in memory quadrant during the probe test. Offspring from high-fat fed dams consuming excess saturated fat spent the least. The levels of mRNA and protein for brain-derived neurotrophic factor and activity-regulated cytoskeletal associated protein were significantly decreased by maternal diet effects. Nerve growth factor mRNA and protein levels were significantly reduced in response to both maternal and postweaning high-fat diets. Expression levels for the NMDA receptor subunit, NR2B, as well as synaptophysin were significantly decreased in response to both maternal and post-weaning diets. Synaptotagmin was significantly increased in offspring from high-fat fed dams. These data support the hypothesis that exposure to excess saturated fat during hippocampal development is associated with complex patterns of gene expression and deficits in learning and memory.