Inhibitory Interneurons in the Cerebral Cortex of Tourette Syndrome (year 2)

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

Tourette’s 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. Although imaging studies have revealed small decreases in the volume of portions of the basal ganglia in TS patients, these studies do not answer the question of whether there are cellular abnormalities in the brain tissue. In our study we are using postmortem brain tissue from four people with TS and comparing these samples to similar tissue from unaffected people (normal controls—NC). With TSA funding, so far we have analyzed the brains from three subjects of each group. We first assessed the number and density of neurons and glial cells in several sub-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), but was increased in the internal segment of the globus pallidus (GPi). In contrast, the number of glial cells was not altered in any of these regions. To confirm these data, we extended our analyses to a type of inhibitory neurons identified by Parvalbumin (PV) immunostaining. Again, the density and number of PV-containing neurons was decreased in the Cd and increased in the GPi of TS subjects. These studies suggest an abnormal distribution of inhibitory neurons in the basal ganglia of TS individuals. However, these findings need to be confirmed in a larger cohort of patients and controls. Preliminary analyses also suggest that fewer PV neurons may be present in the insular cortex of TS subjects. Whether this finding is restricted to the insular cortex will require further investigations. Currently we are extending our analysis to include various regions of the cerebral cortex, and we are also examining the distribution of other types of inhibitory neurons, such as those containing calretinin. Because different types of inhibitory cells are critical for the regulation of neuronal excitability and information processing in the cortico-basal ganglia circuitry, our results may have direct implications for the understanding of neuronal function in TS. Flora Vaccarino, M.D. Yale Child Study Center, New Haven, Connecticut Award: $74,558 Tourette Association of America Inc. – Research Grant Award 2005-2006