Dopaminergic dysfunction has been a primary suspect in Tourette syndrome’s pathophysiology; however, dopaminergic modulation does not lead, by itself, to the formation of motor tics in animal models. Motor tics may be induced experimentally following GABAA antagonists (such as bicuculline) microinjection in the motor domain of the striatum of both rodents and primates. Previous funding by the TSA enabled our group to study the neurophysiological basis of these experimentally induced tics. In this project we will study the involvement of dopaminergic input to the striatum on both the tic expression state, via tonic dopamine levels, and the timing of individual tics, via phasic dopamine release. The underlying hypothesis of the project is that dopamine modulates the primary mechanism of tic formation which is generated by abnormal local GABAergic disinhibition within the striatum. We will use the rodent model of the disorder to study the interaction of the GABAergic and dopaminergic systems. We will test the effects of pharmacological dopaminergic agents and electrical stimulation of the dopaminergic afferents to the striatum on the manifestation of tics and on the neurophysiological encoding of those tics in the cortico-basal ganglia system. The usage of multi-wire electrode arrays implanted in the freely behaving rats will enable the recording of neuronal correlates of motor tics during multiple states: normal behavior, tic formation and dopaminergic modulation of these tics. Moreover, these chronic recordings enable the assessment of individual neuron activity throughout multiple days using different manipulations of the tic expression. The interaction of these key neurotransmitter and neuromodulator systems of the striatum may serve a crucial role in understanding the mechanism underlying the formation and expression of tics in Tourette syndrome. Izhar Bar-Gad, Ph.D. Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel Award: $150,000 Tourette Association of America Inc. – Research Grant Award 2013-2014