Sequential super-stereotypy of an instinctive fixed action pattern in hyper-dopaminergic mutant mice: a model of obsessive compulsive disorder and Tourette's

We found that the serial pattern of this instinctive behavioral sequence becomes strengthened as an entire entity in hyper-dopaminergic mutants, and more resistant to interruption. Hyper-dopaminergic mutant mice have stronger and more rigid syntactic grooming chain patterns than wild-type control mice. Mutants showed sequential super-stereotypy in the sense of having more stereotyped and predictable syntactic grooming sequences, and were also more likely to resist disruption of the pattern en route, by returning after a disruption to complete the pattern from the appropriate point in the sequence. By contrast, wild-type mice exhibited weaker forms of the fixed action pattern, and often failed to complete the full sequence.Sequential super-stereotypy occurs in the complex fixed action patterns of hyper-dopaminergic mutant mice. Elucidation of the basis for sequential super-stereotypy of instinctive behavior in DAT knockdown mutant mice may offer insights into neural mechanisms of overly-rigid sequences of action or thought in human patients with disorders such as Tourette's or OCD.Overly rigid sequential patterns of movement and thought characterize several human brain disorders involving dysfunction in basal ganglia systems (i.e. dopamine nigrostriatal projections to the neostriatum and related brain structures). For example, pathological repetitions of spoken words in Tourette's syndrome, and the tormenting habits and thoughts of obsessive-compulsive disorder (OCD), involve overly rigid sequential patterns of action, language or thought [1-9], which in part may be influenced by genetic factors [10-13].Normal sequential patterns of action, language and thought also have been suggested to depend on proper basal ganglia function [14,15]. For example, Marsden proposed that "The sequencing of motor action and the sequencing of thought could be a uniform function carried out by the basal ganglia" [15], and a variety of computational models have been proposed to carry out