Evidence for a direct subthalamo-cortical loop circuit in the rat

The subthalamic nucleus (STN), a major component of the basal ganglia (BG), plays a crucial role in motor activity and cognitive functions. In current models of the BG, the STN is considered to act by activating the gamma-aminobutyric acid (GABA)ergic neurons of the BG output nuclei, thus inhibiting their thalamic and brain stem targets. However, in addition to the BG output nuclei, the STN has also been reported to innervate the cerebral cortex and the striatum. Here, the anatomo-functional organization of STN projections to the cerebral cortex was investigated using anatomical and electrophysiological approaches. First, wheatgerm agglutinin-conjugated horseradish peroxidase was injected into defined areas of the cerebral cortex to analyse the spatial distribution of retrogradely labelled STN neurons. The mode of cortical innervation by the STN was then determined using extracellular deposits of Phaseolus vulgaris-leucoagglutinin into the STN. Finally, the functional organization of the cortico-STN relationships was investigated by extracellularly recording single STN units antidromically driven from the cerebral cortex. Our results indicate that STN innervates the sensory-motor and prefrontal cortices, the densest projections terminating in cortical layers I-III of the orofacial motor area. The matching between the topographic distribution of subthalamo-cortical neurons and cortico-subthalamic projections forms the basis of a functional cortico-STN loop circuit that is partially opened. In pathological situations such as Parkinson's disease and epilepsy, the STN-cortex loop circuit might contribute to propagate pathological oscillations favouring the emergence of abnormal synchronized activities and a loss of functional selectivity in the cortico-BG network.