Objectives: Alterations in HGF/SF sensitivity in neurons leads to anatomical deficits in the frontal cortex of adult animals. These deficits affect a particular type of interneuron, the fast spiking parvalbumin interneurons. This study used multiple lines of mice, those with increase or reduction of HGF/SF through development. These mice were behaviorally tested on reversal learning tasks to understand the cognitive implications of altered prefrontal GABAergic tone.
Methods: These studies used transgenic mutant mouse lines with behavioral and electrophysiological techniques to understand the role of GABA in both simple elicited behaviors and more complex cognitive tasks, mirroring human tasks.
Results: Reduction in the number of GABAergic interneuron in the adult prefrontal cortex leads to increased anxiety, deficits in tasks of behavioral flexibility, increased seizure susceptibility and deficits in learning and memory. The postnatal addition of supplemental HGF/SF can rescue the anatomical deficits as well as several of the behavioral deficits; however the rescue merely altered the learning and memory deficit.
Conclusions: These data suggest that GABAergic tone may have important implications for understanding complex disorders such as autism spectrum disorder. Changes in the GABAergic tone of the prefrontal cortex may lead to different abilities to handle tasks requiring different cognitive load. This in turn, may manifest itself in more broad and widespread cognitive deficits, such as observed across autism spectrum disorder.