Animal Models of Tourette Syndrome—From Proliferation to Standardization

Abstract

Tourette syndrome (TS) is a childhood onset disorder characterized by motor and vocal tics and associated with multiple comorbid symptoms. Over the last decade, the accumulation of findings from TS patients and the emergence of new technologies have led to the development of novel animal models with high construct validity. In addition, animal models which were previously associated with other disorders were recently attributed to TS. The proliferation of TS animal models has accelerated TS research and provided a better understanding of the mechanism underlying the disorder. This newfound success generates novel challenges, since the conclusions that can be drawn from TS animal model studies are constrained by the considerable variation across models. Typically, each animal model examines a specific subset of deficits and centers on one field of research (physiology/genetics/pharmacology/etc.). Moreover, different studies do not use a standard lexicon to characterize different properties of the model. These factors hinder the evaluation of individual model validity as well as the comparison across models, leading to a formation of a fuzzy, segregated landscape of TS pathophysiology. Here, we call for a standardization process in the study of TS animal models as the next logical step. We believe that a generation of standard examination criteria will improve the utility of these models and enable their consolidation into a general framework. This should lead to a better understanding of these models and their relationship to TS, thereby improving the research of the mechanism underlying this disorder and aiding the development of new treatments.

Global network modulation during thalamic stimulation for Tourette syndrome

“…While recent studies in rodents has demonstrated that interactions between the PT and motor cortex determine where (PT) and when (motor cortex) tics will occur ( Israelashvili and Bar-Gad, 2015 ; Yael et al, 2016 ), our results also support an extended network model and replicate previous findings showing significant activation/abnormality of the cerebellum during the production of tics ( Bohlhalter et al, 2006 ; Lerner et al, 2007 ; Stern et al, 2000 ), and that the cerebellum is an integral part of the tic generating network. The cerebellum is known to have direct and indirect connections with the BG via intralaminar thalamic nuclei ( Hoshi et al, 2005 ).…”

Aripiprazole Selectively Reduces Motor Tics in a Young Animal Model for Tourette’s Syndrome and Comorbid Attention Deficit and Hyperactivity Disorder

“…Underpinning the circuit underlying such a result was not the focus of this study, but it connects with the call for standardization of the preclinical model for TS due to the still remaining confusion between these two motor phenomena (tics and stereotypies) often used in the tic-model literature with an interchangeable meaning ( 36 ). Tic-like movements in animal models are often confused with stereotypies, though they are separated clinical entities.…”

Tourette’s syndrome and its borderland

“…The cause of tic production and the resting state of the brain in TS has been explored with neurophysiology and structural/functional imaging (each using many modalities), small scale but influential postmortem and transcriptome work34 and increasingly relevant animal models 35. There is very clearly a neurological substrate but it is not yet fully understood.…”