Autism spectrum disorders (ASDs) affect approximately 1 percent of the worldwide population and are associated with cognitive deficits in perception, social interaction and communication; these functions are all acquired in the first years of life and are served by the cerebral cortex.
Recent evidence suggests disruption of GABAergic inhibitory interneurons in the brain as a common candidate mechanism underlying ASD. Synthesis of GABA, GABA receptor expression levels and total numbers of inhibitory interneurons are altered in ASDs. In addition, ASDs are associated with altered gamma oscillations and high co-morbidity for epilepsy, two forms of patterned brain activity regulated by GABAergic signaling. However, little is known about the relationship between GABAergic cellular dysfunction throughout development, altered neural network activity and cognitive impairments in ASDs.
Human genetic studies have identified hundreds of risk genes associated with ASD, including MEF2C, a gene encoding a transcriptional factor that plays a role in synaptic development. The goal of the current project is to determine the developmental role of GABAergic dysfunction in regulating sensory processing of cortical networks and behavior in the Mef2C knockout mouse model of ASD. Using a powerful combination of genetic manipulation, optical tools, electrophysiology and behavior, Renata Batista-Brito will determine the cell-type-specific impact of Mef2C deletion on cortical activity in awake-behaving animals.