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

The pathophysiology of idiopathic dystonia, characterized by sustained twisting movements and postures, is still unknown. Clinically, however, the basal ganglia are thought to be the main causative origin of idiopathic dystonia. In the dtsz 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 dtsz hamster revealed a decreased dopamine D1 and D2 receptor binding and an increased [3H]-2-deoxyglucose uptake in the dorsomedial caudate-putamen (CPu), a region supposed to be critically involved in dystonia. Therefore, we were interested whether the spontaneous firing rate of dorsomedial striatal neurons is age-dependently altered in comparison to age-matched non-dystonic control hamsters. Extracellular recordings of spontaneous single unit activity of dorsomedial and ventromedial Type II striatal neurons, i.e., biphasic positive-negative action potentials, from fentanyl anesthetized animals revealed a drastically increased firing rate in the dorsomedial CPu of mutants during age of maximum severity of dystonia. In post-dystonic dtsz hamsters, i.e., after remission of stress-inducible dystonia, no significant differences regarding the dorsomedial CPu could be obtained. We conclude that the dorsomedial subregion of the CPu seems to be critically involved in the dystonic syndrome of dtsz hamsters and that a transiently reduced inhibitory control over excitatory cortico-striatal processes, possibly due to an altered development of GABAergic inhibition, occurs during ontogenesis in dtsz hamsters.