Presenting Author:

Ruoqi Gao

Principal Investigator:

Peter Penzes, Ph.D.

Department:

Physiology

Keywords:

interneurons, epilepsy, mental disorder, E/I balance

Location:

Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital

B164 - Basic Science

Cortical GABAergic Interneuron Regulation by Mental Disorder Susceptibility Molecule Cntnap2

While complex neuropsychiatric disorders have equally complicated genetic etiologies, recent research revealed common disruptions of individual genes across multiple diseases, suggesting similar pathological mechanisms. For example, several genetic studies have established contactin-associated protein-like 2 (CNTNAP2) as a risk gene in mental disorders such as autism spectrum disorders, schizophrenia, epilepsy, and intellectual disability. Studying the function of CNTNAP2, therefore, can lead to unprecedented insight into shared susceptibility pathways of mental diseases. CNTNAP2 is a member of the neurexin superfamily, is highly expressed in the brain, and clusters potassium channels in the axon’s juxtaparanodes. However, its function outside of the axon is less explored. Recent studies of CNTNAP2 knock-out mice revealed not only behavioral abnormalities and epileptic seizures, but also reductions of cortical interneurons and abnormal neuronal synchrony (Peñagarikano et al., 2011). In addition, CNTNAP2 knockdown in primary neuronal culture resulted in the reduction of both excitatory and inhibitory transmission (Anderson et al., 2012).Taken together, these data implicate CNTNAP2 in controlling E/I balance and behavior, possibly through cortical interneuron function. Indeed, epilepsy - an E/I imbalance disorder - is a common core phenotype of many human subjects with CNTNAP2 disruption (Rodenas-Cuadrado et al., 2014). However, mechanistic studies verifying this hypothesis have not yet been established. To this end, we used a wide array of techniques including yeast-2-hybrid screening, confocal and high resolution imaging, biochemistry, and primary neuronal culture, to dissect CNTNAP2’s role in cortical interneuron function and to uncover novel interaction candidates involved with this process.