Inhibitory Interneurons in Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale Child Study Center
Investigators Name
Vaccarino, Flora, MD

Tourette Syndrome (TS) is a childhood-onset neuropsychiatric illness characterized by motor and vocal tics. Regions of the cerebral cortex working together with the basal ganglia regulate motor habits and goal-directed behavior. Imaging studies have revealed a small volumetric decrease in the basal ganglia of patients with TS. In our study we are analyzing the detailed cellular organization of brain tissue from deceased patients with TS and comparing it with similar tissue obtained from unaffected people (normal controls—NC). So far we have compared the brains of four TS and NC people. We first analyzed the number and density of neurons and glial cells (a type of brain cell) in several regions of the basal ganglia. We observed that neuronal density was decreased in the Caudate nucleus (Cd) and in the external segment of the globus pallidus (GPe). However density increased in the internal segment of the globus pallidus (GPi), which is the final output station of the basal ganglia and connects to the thalamus (a region that analyzes sensory stimuli and relays information to the motor regions in the cerebral cortex.) In contrast, the number of glial cells was not altered in any of these regions. To confirm these data, we extended our analyses to different types of inhibitory neurons identified by parvalbumin (PV) and calretinin (CR) immunostaining. The number of both the PV- and CR-containing neurons was decreased in the Cd of TS as compared to NC subjects. However, PV neurons were increased in the GPi. Although these results need to be replicated in a larger cohort of affected and control tissues, they do suggest that there is an abnormal distribution of inhibitory neurons in the basal ganglia of TS individuals, possibly due to an abnormality of their migration during brain development. We also found a decreased density of PV neurons in the insular cortex of TS, but more studies are needed to determine whether this finding is restricted to this particular cortical region. In future studies we will examine the distribution of other types of inhibitory neurons and will extend our analysis to other regions of the basal ganglia and cerebral cortex. Since different types of inhibitory cells are critical for the regulation of neuronal excitability and information processing in the cortico-basal ganglia circuitry, our results could have direct implications for the understanding of neuronal function in TS. Flora M. Vaccarino, M.D. Yale Child Study Center, New Haven, Connecticut Award: $74,195 Tourette Association of America Inc. – Research Grant Award 2006-2007