We are amassing important knowledge about the fundamental genetic and molecular basis of autism spectrum disorder (ASD) and related intellectual disability, but how close are we to understanding how molecular differences cause ASD symptoms? Animal models and a systems approach can help close this gap in understanding and perhaps identify strategies to target outcomes rather than causes.
In this lecture, André Fenton will discuss work with mouse genetic models of fragile X syndrome (FXS), the most common single-gene cause of ASD symptoms, focusing on the utility of such models to evaluate hypotheses for understanding ASD. He’ll evaluate distinct hypotheses by assessing synapse function and the action potential discharge of knowledge-expressing “place cells” during behaviors that require varying cognitive effort. Despite abnormalities in synaptic function within the hippocampus, FXS-mimicking mutations do not disrupt the functioning of individual hippocampal neurons; rather the mutations lead to the discoordination of when those neurons interact. These observations offer novel explanations for inflexibilities in expression of knowledge, learning deficits and inflexible behavior and suggest novel therapeutic strategies that should be evaluated. Such therapeutic strategies are aimed at improving function without directly targeting the molecular foundations of FXS.