Changes in dynorphin immunoreactivity but unaltered density of enkephalin immunoreactive neurons in basal ganglia nuclei of genetically dystonic hamsters

Dystonia is regarded as a basal ganglia disorder. In the dtsz hamster, a genetic animal model of paroxysmal dystonia, previous studies demonstrated a reduced density of striatal GABAergic interneurons which inhibit striatal GABAergic projection neurons. Although the disinhibition of striatal GABAergic projection neurons was evidenced in the dtsz hamster, alterations in their density have not been elucidated so far. Therefore, in the present study, the density of striatal methionin-(met-) enkephalin (ENK) immunoreactive GABAergic neurons, which project to the globus pallidus (indirect pathway), was determined in dtsz and control hamsters to clarify a possible role of an altered ratio between striatal interneurons and projection neurons. Furthermore, the immunoreactivity of dynorphin A (DYN), which is expressed in entopeduncular fibers of striatal neurons of the direct pathway, was verified by gray level measurements to illuminate the functional relevance of an enhanced striato-entopeduncular neuronal activity previously found in dtsz hamsters. While the density of striatal ENK immunoreactive (ENK+) neurons did not significantly differ between mutant and control hamsters, there was a significantly enhanced ratio between the DYN immunoreactive area and the whole area of the EPN in dtsz hamsters compared to controls. These results support the hypothesis that a disbalance between a reduced density of striatal interneurons and an unchanged density of striatal projection neurons causes imbalances in the basal ganglia network. The consequentially enhanced striato-entopeduncular inhibition leads to an already evidenced reduced activity and an altered firing pattern of entopeduncular neurons in the dtsz hamster. Synapse 2011. © 2011 Wiley-Liss, Inc.