Parkinsonism originates in a discrete secondary and dystonia in a primary motor cortical-basal ganglia subcircuit

Abstract

Abstract Although manifesting contrasting phenotypes, Parkinson’s disease and dystonia originate from similar pathophysiology. Previously, we lesioned a discrete dorsal region in the globus pallidus (rodent equivalent to globus pallidus externa) in rats and produced parkinsonism, while lesioning a nearby ventral hotspot induced dystonia. Presently, we injected anterograde fluorescent-tagged anterograde multi-synaptic tracers into these pallidal hotspots. Viral injections in the Parkinson’s hotspot fluorescent labeled a circumscribed region in the secondary motor cortex, while injections in the dystonia hotspot labeled within the primary motor cortex. Custom probability mapping and N200 staining affirmed the segregation of the cortical territories for Parkinsonism and dystonia to the secondary and primary motor cortices. Intracortical microstimulation localized territories specifically to their respective rostral and caudal microexcitable zones. Parkinsonian features are thus explained by pathological signaling within a secondary motor subcircuit normally responsible for initiation and scaling of movement, while dystonia is explained by abnormal (and excessive) basal ganglia signaling directed at primary motor corticospinal transmission.