Modeling tics in rodents: Conceptual challenges and paths forward

Abstract

Background: Recent advances in our understanding of the neurobiology of tics have led to the development of novel rodent models capturing different pathophysiological and phenotypic aspects of Tourette syndrome. The proliferation of these models, however, raises vexing questions on what standards should be adopted to assess their theoretical validity and empirical utility. Assessing the homology of a rodent motoric burst with a tic remains problematic, due to our incomplete knowledge of the underpinnings of tics, their high phenotypic complexity and variability, limitations in our ability test key aspects of tic phenomenology (such as premonitory sensory phenomena) in animals, and between-species differences in neuroanatomy and behavioral repertoire. These limitations underscore that any interpretation of behavioral output in an animal model cannot exclusively rely on the recognition of features that bear superficial resemblance with tics, but must be supported by other etiological and convergent phenomenological criteria.

New method: Here, we discuss two complementary approaches for the study and validation of tic-like manifestations in rodents, based respectively on the use of contextual modulators and accompanying features of repetitive motor manifestations and on the reproduction of pathogenic factors.

Results: Neither strategy can by itself provide convincing evidence that a model informatively recapitulates tic pathophysiology. Their combination holds promise to enhance the rigorous evaluation and translational relevance of rodent models of tic disorders.

Conclusions: This systematic consideration of different approaches to the validation and study of animal models of tic pathophysiology provides a framework for future work in this area.

Keywords: Animal model; Basal ganglia; Grooming; Stereotypy; Tics; Tourette syndrome.