Alterations in spontaneous single unit activity of striatal subdivisions during ontogenesis in mutant dystonic hamsters

The pathophysiology of idiopathic dystonia, characterized by sustained twis ting movements and postures, is still unknown. Clinically, however, the bas al ganglia are thought to be the main causative origin of idiopathic dyston ia. In the dt(sz) hamster, a genetic animal model for idiopathic paroxysmal dystonia, the attacks occur in response to mild stress and the severity of dystonia is age-dependent. Previous autoradiographic studies in the drs' h amster revealed a decreased dopamine D1 and D2 receptor binding and an incr eased [H-3]-2-deoxyglucose uptake in the dorsomedial caudate-putamen (CPu), a region supposed to be critically involved in dystonia. Therefore, we wer e interested whether the spontaneous firing rate of dorsomedial striatal ne urons is age-dependently altered in comparison to age-matched non-dystonic control hamsters. Extracellular recordings of spontaneous single unit activ ity of dorsomedial and ventromedial Type II striatal neurons, i.e., biphasi c positive-negative action potentials, from fentanyl anesthetized animals r evealed a drastically increased firing rate in the dorsomedial CPu of mutan ts during age of maximum severity of dystonia. In post-dystonic dt(sz) hams ters, i.e., after remission of stress-inducible dystonia, no significant di fferences regarding the dorsomedial CPu could be obtained. We conclude that the dorsomedial subregion of the CPu seems to be critically involved in th e dystonic syndrome of dt(sz) hamsters and that a transiently reduced inhib itory control over excitatory cortico-striatal processes, possibly due to a n altered development of GABAergic inhibition, occurs during ontogenesis in dt(sz) hamsters. (C) 1999 Elsevier Science B.V. All rights reserved.