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

Abstract

Recent studies have shown a dramatically decreased spontaneous discharge rate of entopeduncular neurons in a unique animal model of idiopathic paroxysmal dystonia, the dt(sz) mutant hamster. These changes were found in animals at the age at which the most marked expression of dystonia is usually observed. In this rodent model, the age-dependent disappearance of stress-inducible dystonic attacks at an age of approximately 10 weeks allows investigations of the relevance of pathophysiological changes for the occurrence of dystonia by ontogenetic studies. Therefore, we examined the entopeduncular activity by extracellular single unit recordings in groups of dt(sz) mutants and nondystonic control hamsters at 17-22 weeks of age. In contrast to recent findings, after the complete remission of dystonia, the mean discharge rate of entopeduncular neurons in dt(sz) mutants (28.1 +/- 1.2 spikes/sec) was 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 present data clearly demonstrate the fundamental importance of a decreased basal ganglia output for the expression of paroxysmal dystonia.