Spontaneous remission of paroxysmal dystonia coincides with normalization of entopeduncular activity in dt(sz) mutants

Recent studies have shown a dramatically decreased spontaneous discharge ra te of entopeduncular neurons in a unique animal model of idiopathic paroxys mal dystonia, the dt(sz) mutant hamster. These changes were found in animal s at the age at which the most marked expression of dystonia is usually obs erved. In this rodent model, the age-dependent disappearance of stress-indu cible dystonic attacks at an age of similar to 10 weeks allows investigatio ns of the relevance of pathophysiological changes for the occurrence of dys tonia by ontogenetic studies. Therefore, we examined the entopeduncular act ivity by extracellular single unit recordings in groups of dt(sz) mutants a nd nondystonic control hamsters at 17-22 weeks of age. In contrast to recen t findings, after the complete remission of dystonia, the mean discharge ra te of entopeduncular neurons in dt(sz) mutants (28.1 +/- 1.2 spikes/sec) wa s similar to that of age-matched nondystonic control hamsters (30.8 +/- 0.9 spikes/sec). Thus, the disappearance of paroxysmal dystonia is accompanied by a normalization of the entopeduncular activity in dt(sz) mutants. The p resent data clearly demonstrate the fundamental importance of a decreased b asal ganglia output for the expression of paroxysmal dystonia.