Unbalanced Inhibitory Function in Tourette Syndrome: Insights from Novel Animal Model

Grant Type
Basic
Grant Year
2008-2009
Institution Location
Foreign
Institution Organization Name
CSIC & Univ. Miguel Hernandez Spain
Investigators Name
Marin, Oscar, PhD

Tourette Syndrome (TS) is a neuropsychiatric illness characterized by motor and vocal tics. A considerable amount of data implicates TS with abnormal functioning of the basal ganglia, a richly interconnected set of nuclei located in the base of the brain that regulate motor habits and goal-directed behavior. Because the basal ganglia participate in the execution and learning of stereotyped repetitive behaviors or habits, it is conceivable that abnormal functioning of these circuits may underlie the development of TS. However, despite intense research over the past decades, neither the cause nor the mechanism underlying the development of TS is well understood. Both genetic and environmental factors are thought to be important, but the exact role of each has not yet been identified. The function of neural circuits in the brain emerges from the interaction between two types of neurons – excitatory and inhibitory. Recent reports suggest that there is a profound imbalance in the distribution of Parvalbumin-containing (PV) inhibitory neurons in the basal ganglia of people with TS. Since inhibitory cells are critical for the regulation of neuronal excitability and information processing in the basal ganglia circuitry, these results provide a plausible biological explanation for the functional defects found in TS. The main goal of our project is to understand the possible developmental mechanisms that may lead to an abnormal distribution of PV containing (PV+) inhibitory neurons in the basal ganglia. In addition, we plan to generate a mouse model of the disorder by specifically ablatingPV+ inhibitory neurons in the basal ganglia of transgenic mice. Analysis of this mouse model will tell us whether the loss of PV+ interneurons in the basal ganglia causes alterations in the execution and learning of motor behaviors. We hope that this model may eventually become a very useful tool in the TS field. Oscar Marin, Ph.D. Institute of Neuroscience, CSIC & University Miguel Hernandez, Campus de San Juan, Alicante, Spain Award: $74,000 Tourette Association of America Inc. – Research Grant Award 2008-2009