André Fenton and his group at New York University hypothesize that a common pathophysiology underlies the failures of cognitive flexibility that are characteristic of autism. Fenton aims to investigate the widely held ‘discoordination’ hypothesis that in individuals with autism, the neural computations within and between networks of cells that depend upon precisely coordinated neural activity are impaired.

Fenton assumes the impairments derive from inappropriate transmission across neuronal junctions, or synapses. This interferes with the ability of neurons to coordinate their electrical discharge to maintain and switch between separate streams of information flow through neuronal networks.

Fenton and his colleagues plan to evaluate the discoordination hypothesis by measuring neural coordination in the action-potential discharge of hippocampus place cells and by measuring the ongoing hippocampal local field potentials. They plan to concurrently evaluate basic cognitive behavior and cognitive flexibility in freely behaving mutant mouse models relevant to autism research.

Data will be collected from control mice and three mutant mouse strains that mimic genetic abnormalities seen in autism. Specifically, Fenton and his group aim to study mice lacking FMR1, mice missing one copy of TSC2, and mice with a microdeletion on chromosome 16. These mice model the autism-related disorders fragile X syndrome, tuberous sclerosis complex and human chromosomal region 22q11.2 deletion, respectively. The researchers aim to record single-unit ensembles and local field potentials during concurrent cognitive behaviors of freely behaving mice.