title: Towards a primate model of Gilles de la Tourette syndrome: anatomo-behavioural correlation of disorders induced by striatal dysfunction.
abstract: BACKGROUND
  Gilles de la Tourette syndrome (GTS) is characterized by abnormal movements (tics) often associated with behavioural disorders. Neuropathological data from GTS patients have suggested that aberrant activation of distinct striatal functional territories could produce a large spectrum of GTS symptoms. In a monkey model, injections of GABA-antagonist into the striatum enabled us to produce tic-like movements, hyperactivity and stereotyped behaviours. These effects had similarities with simple motor tics, hyperactivity and compulsive behaviours observed in GTS patients. In this study, we first aimed to identify the neuronal circuits involved in the different behavioural effects using anatomical antero/retrograde tracer in monkeys. We also compared the neuronal circuits thus obtained with the available neuro-anatomical data on GTS patients.
  
  
  METHODS
  Using injections of axonal tracer into different functional parts of the striatum of eight monkeys, we identified cortical, thalamic and basal ganglia regions related to the expression of tic-like movements, hyperactivity and stereotyped behaviours induced in response to microinjection of GABA-antagonist.
  
  
  RESULTS
  In this monkey model, different anatomical circuits involving distinct cortical and thalamic areas and sub-territories of the basal ganglia underpinned movement and behavioural disorders. Thus, tic-like movements were associated with neuronal labelling within the sensorimotor network, mostly in the medial and lateral premotor cortex and sensorimotor parts of the basal ganglia. Neuronal labelling in the prefrontal dorso-lateral cortex and associative territories of the basal ganglia was related to hyperactivity disorder and stereotyped behaviours were linked to the orbitofrontal cortex and limbic part of the basal ganglia.
  
  
  CONCLUSIONS
  These results support the hypothesis that different behavioural effects could arise from distinct but inter-digitated neuronal circuits. As these behavioural disorders shared some similarities with simple motor tics, hyperactivity and compulsive behaviours observed in GTS patients, this model could be a good tool for future studies involving the modulation of neuronal circuits, such as deep brain stimulation.
authors.affiliation: UPMC Université Paris 6, UMR-S975, CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Worbe
authors.forename: Véronique
authors.initials: V
authors.lastname: Sgambato-Faure
authors.forename: Justine
authors.initials: J
authors.lastname: Epinat
authors.forename: Marion
authors.initials: M
authors.lastname: Chaigneau
authors.forename: Dominique
authors.initials: D
authors.lastname: Tandé
authors.forename: Chantal
authors.initials: C
authors.lastname: François
authors.forename: Jean
authors.initials: J
authors.lastname: Féger
authors.forename: Léon
authors.initials: L
authors.lastname: Tremblay
mesh_terms: D000344:Afferent Pathways / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000473:pathology / Q000503:physiopathology; D018756:GABA Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D008845:Microinjections; D017072:Neostriatum / Q000503:physiopathology*; D013239:Stereotyped Behavior; D005879:Tourette Syndrome / Q000139:chemically induced / Q000473:pathology / Q000523:psychology*
chemical_list: D018756:GABA Antagonists; D001640:Bicuculline