One feature of Tourette’s Syndrome (TS) is a disruption in sensorimotor gating, a preattentional information-filtering mechanism whose dysfunction may contribute to the symptoms of this illness. Prepulse inhibition (PPI) is an operational measure of sensorimotor gating, and is disrupted in TS patients. Recent findings from our lab demonstrate that noradrenergic (NE) receptors, and in particular NE-containing afferents originating in the locus coeruleus, potently regulate PPI in adulthood. TS, however, first presents during earlier timepoints when such neural systems are not yet fully developed, including the period spanning adolescence. Correspondingly, little is known about NE system regulation of PPI during childhood / adolescence. Given that NE-based drugs such as guanfacine and clonidine are effective in the treatment of TS, it has been argued that NE system dysfunction during development may contribute to TS. The present proposal will utilize a rodent model to investigate if differential sensitivity of central NE pathways during the period corresponding to childhood / adolescence (compared to adulthood) is in part responsible for PPI deficits that have been reported previously for patients with TS, and determine the specific neuroanatomical substrates through which NE-based drugs might improve such functions in this illness. These experiments may provide a detailed new understanding of the basic neurobiological underpinnings of sensorimotor gating abnormalities in TS, and developmental NE-based mechanisms of action for effective treatments for this illness. Vaishali Bakshi, Ph.D. University of Wisconsin School of Medicine and Public Health, Madison, WI Award: $$149,985 Tourette Association of America Inc. – Research Grant Award 2012-2013