Interactions of the Histamine and Dopamine Systems in Tourette Syndrome

Grant Type
Basic
Grant Year
2014-2015
Institution Location
CA
Institution Organization Name
University of California
Investigators Name
Chung, Shinjae, PhD

Tourette syndrome is a neurological disorder that affects many children and adults. It is characterized by stereotyped involuntary movements, and the etiology of TS is poorly understood. Current therapies have some efficacy in reducing tics, but are associated with aversive side effects. Therefore, new approaches are needed to develop better therapeutics. This proposal aims at understanding how the balance/interaction of dopamine and histamine neurotransmission may be crucial for the symptoms of people with TS. Because the histamine system is present in the circuitry in which the dopamine system is thought to affect TS, I propose to analyze whether manipulating the histamine neurotransmission may affect TS pathophysiology using animal models relevant to the TS. The aims of this study are: SPECIFIC AIM 1: To determine whether optogenetic activation or suppression of the histamine system affects apomorphine-induced prepulse inhibition (PPI) disruption and stereotyped behaviors, two behaviors associated with the TS. SPECIFIC AIM 2: To understand anatomical interactions of the histamine and the dopamine systems, I propose to use rabies virus-mediated circuit mapping tools to understand monosynaptic interaction between these two systems. Therefore, this proposed project takes a major step in addressing fundamental questions understanding interactions of the histamine and dopamine circuits underlying TS symptoms using state-of-the-art-techniques. A combination of these techniques will provide a unique opportunity for understanding anatomical, physiological and functional interactions between the histamine and dopamine systems. This study will advance our understanding of the biology of TS with an ultimate goal that may enable the development of novel therapies for TS and other neurological conditions. Shinjae Chung, Ph.D., Yang Dan, Ph.D., Olivier Civelli, Ph.D. University of California, Berkeley, Berkeley, CA Award: $40,000 (Fellowship) Tourette Association of America Inc. – Research Grant Award 2014-2015