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 decrease in three classes of striatal interneurons in the striatum of TS: Parvalbumin; NOS/NPY/SST; and cholinergic (Kalanithi et al, 2005; Kataoka et al, 2010). Transcriptome analysis revealed a corresponding decreased expression in genes related to neurotransmitter signaling and metabolic function, as well as an up-regulation inflammatory response genes (Lennington et al., 2016). 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.

Interneuron loss in TS: Striatal interneuron density is significantly decreased in TS, including NOS+- (above) and PV+-GABAergic, and cholingergic interneurons. In contrast, the density of cells labeled with the pan-immune marker CD-45 is significantly increased.

Generation of medium spiny neurons in basal ganglia organoids grown from iPSC. DAPI, blue; GAD67, green; CTIP2, red. Scale bar 100µm