An Animal Model of Tourette Syndrome: Targeted Ablation of Striatal Fast-Spiking Interneurons

Grant Type
Grant Year
Institution Location
Institution Organization Name
Yale University
Investigators Name
Pittenger, Christopher, MD, PhD

Historically, the development of animal models has been a key step in discovering the mechanisms of complex diseases and paving the road to new therapies. Because of the nature of the disorder and its symptoms, the development of an animal model for Tourette Syndrome (TS) has been challenging. One way to develop a model of TS would be to recapitulate in an animal some genetic, molecular, or neuronal alteration found in the brains of people suffering from the syndrome, but since so little was known about the biological causes of TS, this was impossible. A study recently performed at Yale University revealed that a particular type of interneuron (the fast-spiking interneuron) is numerically reduced in the brains of individuals with severe, treatment-resistant Tourette Syndrome. These interneurons are thought to have a critical role in regulating the passage of information through the striatum (a part of the basal ganglia) that associates sensory cues—sounds, touches, sights—with motor actions. When that regulatory function is disrupted, sensory-motor associations are likely to become disorganized, and may be the neurobiological origin of tics. The aim of this study is to recapitulate this regulatory disruption in an animal model by producing genetically altered mice in which the fast-spiking interneurons in the striatum are selectively altered or eliminated. Observing the behavioral consequences of such a disruption could help us understand the association between the reduced number of interneurons and the expression of TS symptoms. For technical reasons, producing such a specific disruption of the striatal fast-spiking interneurons in a mouse will be challenging. In the initial phase of this project, we aim to develop techniques to manipulate (or eliminate) just these specific interneurons and only in the striatum. Once this is accomplished, we will examine the resulting mice in behavioral tests that probe the function of the striatum. These experiments may provide a fruitful model in which to try out new therapeutic strategies. Christopher Pittenger, M.D., Ph.D. Yale University New Haven, CT Award: $72,378 Tourette Association of America Inc. – Research Grant Award 2007-2008