Effects of Dopaminergic Drugs and Cortical Stimulation on the Dye-Coupling in Adult Striatum: Possible Revelance to TS Treatment

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

Tourette Syndrome (TS) is believed to be a developmental disorder with primary deficits in motor control (e.g., hyper-kinetic) with concurrent learning and attentional deficits. The nigrostriatal system appears to be the dopamine (DA) system centrally involved in the pathophysiology of TS. Evidence has indicated that adult rats with neonatal dopamine depletions exhibit self-biting behavior and other abnormal oral movements in response to DA-related drug treatments which simulate some of the aspects of TS. Therefore in the context of an animal model with DA depletions as neonates, this proposed study will examine the impacts on pharmacological responsiveness as well as on intercellular network property by DA-related drugs known to exacerbate or alleviate TS symptoms. This will be accomplished by recording drug responsiveness in an identified neuron by injecting the cell with a fluorescent dye, Lucifer yellow, which is known to completely fill the injected neuron and pass into neighboring neurons electrically coupled to the injected neuron (known as dye-coupling). Dye-coupling among sets of neurons has been hypothesized to provide a basis for intercellular communication among the coupled cells; therefore, any alterations in dye-coupling could play a significant role in the integrating properties of cells which may have impacts as important as measures of single neuronal activity on determining drug responsiveness. In a previous study funded by TSA in 1987, we have established the identification of two functional subsets of medium spiny neurons, termed Type I and Type II cells, in the striatum based on their differential response patterns to the stimulation of prefrontal cortex. We have recently reported that abnormally high levels of neuronal activity in Type II striatal neurons persist into adulthood as dopamine depletions occur at postnatal day 3, despite dopamine depletions during the developmental stage produce little effects on their gross sensorimotor function and ingestive behaviors in the adulthood. Our recent observations have indicated that in normal rats dye-coupling is between single pairs and restricted to one subset (i.e., Type II) of medium spiny neurons. Therefore by treating postnatal day 3 pups with intraventricular 6-hydroxydopamine, this proposed study will examine the incidence and extent of dye-coupling in the adulthood between striatal Type I and Type II cells with respect to the stimulation of prefrontal cortex. Using intracellular recording and Lucifer yellow dye labelling techniques, the pharmacological responsiveness to DA-related drugs, e.g., L-DOPA and amphetamine, can be corresponded with alterations in dye-coupling property in the animal model with a compromised DA system. Shao-Pii Onn, Ph.D. University of Pittsburgh, Pittsburgh, PA Award $23,900 Tourette Association of America Inc. – Research Grant Award 1991