Increased excitability in cortico-striatal synaptic pathway in a model of paroxysmal dystonia

Abstract

Dystonias are movement disorders whose pathomechanism is largely unknown. Dystonic dt sz hamsters represent a model of primary dystonias, where alterations of striatal interneuron density and sodium channel function in projection neurones were described. Here, using cortico-striatal slices, we explore whether also the communication between neocortex and striatum is altered in dt sz hamsters. Field and intracellular recordings were done in dorsomedial striatum. Electrical stimulation was used to mimic neocortical afferents. Neuronal characteristics, synaptic connections, input–output relations and short- and long-term plasticity were analysed. Regarding cellular properties, striatal neurons of affected animals showed no alterations. Concerning network properties, evoked responses at threshold stimulation were mediated by (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors. In dt sz slices, field responses, paired-pulse accentuation and LTP were larger than in control, possibly by an increase in presynaptic release probability at glutamatergic synapses. In summary, the study indicates that a change of cortico-striatal communication is involved in the manifestation of paroxysmal dystonia in the dt sz mutant.