On November 28, 2018, André Fenton discussed work with mouse genetic models of fragile X syndrome (FXS) – the most common single-gene cause of autism spectrum disorder (ASD) symptoms – and focused on the utility of such models to evaluate hypotheses for understanding ASD. He evaluated distinct hypotheses by assessing synapse function and the action potential discharge of knowledge-expressing hippocampus “place cells” during behaviors that require varying cognitive effort.
His talk was part of the Simons Foundation Autism Research lecture series.
About the Lecture
We have been amassing important knowledge about the fundamental genetic and molecular bases of 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 identify strategies to target outcomes rather than causes.
In this lecture, André Fenton discussed work with mouse genetic models of FXS –the most common single-gene cause of ASD symptoms – and focused on the utility of such models to evaluate hypotheses for understanding ASD. He evaluated distinct hypotheses by assessing synapse function and the action potential discharge of knowledge-expressing hippocampus “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 those 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.
About the Speaker
André Fenton is a professor of neural science at New York University. His research focuses on molecular, neural, behavioral and computational aspects of memory. He studies how brains store experiences as memories and how the expression of knowledge activates information that is relevant without activating what is irrelevant. His lab recordings of electrical brain activity are elucidating the physiology of cognitive control and cognitive dysfunction in schizophrenia, intellectual disability and autism. In an effort to integrate investigations and understanding across levels of biological organization, the Fenton lab uses genetic, molecular, electrophysiological, imaging, behavioral, engineering and theoretical methods to investigate these fundamental and interrelated issues in neuroscience.
Fenton and colleagues identified PKMzeta as the first molecule that maintains the persistence of memories in the brain, a discovery recognized by Science Magazine as one of the 10 most important breakthroughs in all of science and technology published in 2006. Fenton founded Bio-Signal Group Corp., which developed and commercialized an FDA-approved portable, wireless and easy-to-use platform for obtaining medical quality electroencephalograms (EEGs) anywhere, anytime and for everyone. It is being used in innovative clinical applications including emergency medicine, sports, space exploration and underserved clinics in Africa. Fenton also co-hosts NOVA Wonderson PBS.
