Nicolas Maurice

The core of the nucleus accumbens (NAcc core) is the principal input structure to the basal ganglia circuitry for the prelimbic and medial orbital areas (PL/MO) of the prefrontal cortex. As is now well recognized in the rat, the main basal ganglia output of this prefrontal channel is the dorsomedial part of the substantia nigra pars reticulata (SNR) and not the ventral pallidum as previously suggested. There is evidence suggesting that the ventral pallidum is rather involved with the subthalamic nucleus (STN) in an indirect NAcc-SNR pathway. Indeed, we have recently shown that the NAcc core sends an inhibitory input to the lateral ventral pallidum (VPl), which projects to the medial STN. In the present study, we injected biocytin into the medial STN, at a site where neurons presented an inhibitory response to VPl stimulation. This produced anterogradely labelled fibres in the medial SNR and in the VPl. Furthermore, the stimulation of the VPl induced an inhibition in a majority of the STN cells identified, by the antidromic activation method, as projecting to SNR (76.6%) and/or back to the VPl (72.7%). In conclusion, these data further demonstrate the existence of an indirect striato-nigral pathway in the PL/MO channel and indicate that VPl is involved in an inhibitory feedback circuit, which modulates the discharge of medial STN. These results indicate that the medial STN is implicated in the limbic/cognitive functions of the basal ganglia.

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 γ-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.