title: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pharmacology and Toxicology, Interdepartmental Neuroscience Program, University of Utah, 30 S 2000 E, Skaggs Hall, Room 3916, Salt Lake City, UT, 84112, USA. Electronic address: marco.bortolato@utah.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Bortolato
authors.affiliation: Department of Psychiatry, Department of Psychology, Child Study Center, Interdepartmental Neuroscience Program, Yale University, 34 Park Street, W315, New Haven, CT, 06519, USA. Electronic address: christopher.pittenger@yale.edu.
authors.forename: Christopher
authors.initials: C
authors.lastname: Pittenger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D012377:Rodentia; D013981:Tic Disorders / Q000235:genetics / Q000503:physiopathology
keywords: Animal model; Basal ganglia; Grooming; Stereotypy; Tics; Tourette syndrome