Effect of Reduced Maternal fmrp Expression on Reversal Learning in Male Mice
Kevin Newhall, Vassar College ’17 and Prof. Bojana Zupan
Dysfunction of the FMR1 gene leads to an absence of Fragile X Mental Retardation Protein (FMRP), causing Fragile X Syndrome (FXS), the most common monogenic form of autism. Mouse fmr1 is homologous to human FMR1, and the fmr1 knock out (KO) mouse models FXS. fmr1 KO mice exhibit behavioral changes such as hyperactivity, abnormal sociability, and learning deficits. One commonality between these behaviors is the neurotransmitter dopamine. Previous studies in our lab have shown that maternal genotype is a marker for dopamine-related behavioral changes in her offspring (Zupan & Toth, 2008). This maternal effect is an intermediary level of behavioral abnormality present in animals whose mothers are heterozygous (H) for the mutation, but are themselves unaffected (wild type). As dopamine can modulate learning, if the maternal effect truly modifies dopamine modulated behaviors, we hypothesize there will be an effect on learning in H dam-derived mice. To test this, we used a reversal learning task, the t-maze. Reversal learning is deficient in fmr1 KO mice, and is defined as the ability to disregard previously learned information in favor of new contradictory information. We show that although there is no difference in the total number of errors made before criterion in either acquisition or reversal between the groups, mice derived from KO or H dams exhibit a reduced number of errors related to perseveration of the previously reinforced arm relative to controls. This suggests they may fail to maintain their knowledge of the previously reinforced arm during reversal training. Our lack of error and trial to criterion differences between the groups suggests the t-maze may not be a sufficiently complex task to detect subtle differences in cognitive processing. Future research plans involve pharmacologic manipulation of dopamine signaling, with the aim of increasing the difficulty of the behavioral tasks and its ability to detect maternal effect/s on reversal learning.