Investigating Habitual Behavior and Cholinergic Modulation of Dopamine Release in Tourette Disorder

2022 Seed Grant
Max A. Tischfield, Ph.D.
Rutgers University

Dr. Tischfield’s laboratory is a member of the Tourette International Genetics Consortium, a global effort spanning multiple continents to decipher the genetic basis of Tourette Syndrome and associated conditions. Their consortium has identified several genes that are affected in Tourette Syndrome, and have used DNA editing technology to introduce human gene mutations in mice. This has allowed us to create the first animal models for Tourette Syndrome that express the identical gene mutations as found in humans. With these novel animal models, we are now able to test new ideas and prevalent hypotheses in the field pertaining to tics and habits in Tourette Syndrome. Dr. Tischfield’s lab will test the hypothesis that perturbations to brain regions that control the formation of habits contribute to tics. Additionally, They will test the hypothesis that dysregulation of dopamine release influences stronger habitual responding in our animal models. To accomplish these goals, Dr. Tischfield’s lab will train their animal models to develop behaviors indicative of habits, and test whether Tourette mice form habits quicker and/or have greater difficulties in breaking habits compared to unaffected siblings. Next, using sophisticated methods that allow us to measure dopamine levels while animals learn to form habits, they will test whether changes to dopamine release in the brain are associated with a greater propensity to form habits in Tourette Syndrome. Altogether, Dr. Tischfield’s work is expected to develop a novel framework centered around habit formation and dopamine that will help us decipher the neurobiological basis of tics. Leveraging this novel framework, They can begin to test pharmacological and/or behavioral interventions that may be more efficacious for treating Tourette Syndrome.

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