Cortico-basal ganglia interactions in movement disorders: Tourette Syndrome

Tourette Syndrome (TS) is a developmental disorder of childhood characterized by motor and vocal tics. Patients with TS have decreased volume of the striatum (a region of the basal ganglia composed by caudate and putamen), and the decrease in caudate volume in childhood is inversely correlated with the severity of symptoms in adulthood. We have shown a large decrease in density of three classes of striatal interneurons in the striatum of TS: Parvalbumin+-GABAergic; NOS+/NPY+/SST+-GABAergic; and cholinergic (Kalanithi et al, 2005; Kataoka et al, 2010). Transcriptome analysis revealed a corresponding decreased expression of 308 genes encompassing genes related to these three classes of interneuron and inhibitory neurotransmission in general, as well as an up-regulation of 822 genes representing inflammatory response- and immune system-related genes (Lennington et al., 2014). Current studies in the lab aim to analyze genetic and epigenetic differences in the striatum and cortex as a whole and within isolated cell types. We also characterize neuronal subtypes generated from TS patient-derived stem cells. Together these strategies may yield new insights into the etiology of TS.