The Relationship of Striatal Organization to the Pathophysiology of Tourette Syndrome

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Pittsburgh
Investigators Name
Onn, Shao-Pii, PhD

The current state of knowledge about the biological basis of Tourette Syndrome is derived solely from considerations of the involuntary motor symptoms associated with this disorder and on the actions of the drugs used in its treatment. From this evidence, the motor systems of the brain, in particular those moving the striatum, have been hypothesized to play a major role in the expression of TS symptoms. However, investigations of this system have been hampered by the lack of knowledge about the interconnections of neurons within the striatum. By studying the way that striatal neurons communicate with each other and how this communication is influenced by motor-related inputs, we hope to extend our knowledge or striatal function into the realm of how individual cells are involved in regulating its actions. This information can then be applied to hypotheses about the manner in which the striatum affects voluntary motor movement and possible breakdown of this process in disease state. The first step in this investigation is to identify the neurons recorded within the striatum. Two sets of criteria will be used to differentiate neurons in this structure: the morphology (shape) of the striatal neurons and how they connect to neighboring neurons, and the neurotransmitter that these neurons use in that communication. This will be accomplished by injecting individual cells with fluorescent dye, Lucifer yellow, which is known to a completely fill the injected neuron and provide a detailed picture of this morphology. Sections of the striatum which contain this stained neuron can then be exposed to be antibodies which only attach to cells containing particular neurotransmitters. By finding cells which are labeled with both the dye and the antibody, we can determine both the structure of the neuron we are studying as well as the neurotransmitter the cell uses in its communications. This type of identification will add greater relevance to our subsequent pharmacological studies where we will determine the way that these newly identified cells react to drugs used in the treatment of Tourette Syndrome. In this way, we hope to use the information about drugs that are effective in the treatment of Tourette Syndrome to identify the cells implicated in the disease process. Shao-Pii Onn, Ph.D. University of Pittsburgh, Pittsburgh, PA Award: $20,000 Tourette Association of America Inc. – Research Grant Award 1987