Rats selectively bred for deficient prepulse inhibition (PPI) of the acoustic startle reaction can be used to study the pathophysiological mechanisms and therapeutic strategies for neuropsychiatric disorders with abnormal information processing, such as Tourette syndrome (TS). We aim to test the effect of deep brain stimulation (DBS) in different regions of the basal ganglia and associated regions in rats selectively bred for high and low PPI, since TS is most likely the result of a dysfunction of information processing within these neuronal circuitries. Specifically, we will compare the effect of chronic DBS in the entopeduncular nucleus (EPN, the equivalent to the human globus pallidus internus), the centromedian-parafascicular complex (CM-Pf), and the nucleus accumbens (NAC) on PPI. Furthermore, we will investigate the possible restorative effect on behavioral flexibility and social behavior of these rats. Since the effect of DBS will likely interact with disturbed neuronal network function, the effect of DBS on single unit activity in the EPN, the CM-Pf, and the NAC will be investigated. These studies will greatly enhance our knowledge of neuronal systems thought to be involved in the pathophysiology of TS. Rats with PPI deficits may help us to find the optimal location for DBS and the best means of stimulation settings for this disorder. They will give new insight into the plasticity and modulation of the basal ganglia circuitry and their modulation by DBS. Recently our colleagues in the departments of Psychiatry and Neurosurgery started a prospective, controlled, randomized clinical study to evaluate the efficiency of DBS in the CM-Pf and the globus pallidus internus (GPi) for the treatment of severe treatment resistant TS. We envision that the concomitant clinical and experimental study may provide additional insights, in particular with regard to the translational aspects of this experimental therapy. . Kerstin Schwabe, Ph.D., Joachim K. Krauss, Ph.D., Mesbah Alam, Ph.D. Hannover Medical School, Hannover, Germany Award: $60,000 Commentary: A breakdown of the mechanisms in the brain to suppress irrelevant information can be related to the inability to suppress tics in Tourette syndrome. Rats selectively bred for deficient information processing are often used as a model to study nerve cell changes and therapeutic strategies for TS. In this study we will test whether Deep Brain Stimulation (DBS) in different brain regions can restore the disturbed information processing in these specially bred rats. Nerve cell activity will be measured to evaluate the effect of the treatment in these rats and to determine how DBS may work. Tourette Association of America Inc. – Research Grant Award 2010-2011