Macro-architecture of basal ganglia loops with the cerebral cortex: use of rabies virus to reveal multisynaptic circuits.

We have used retrograde transneuronal transport of rabies virus to examine basal ganglia connections with the cerebral cortex. We injected rabies into the primary motor cortex (M1) or into Area 46 of cebus monkeys. A 4-day survival time was long enough to allow transport of rabies from the injection site to 'third-order' neurons in the basal ganglia. After either M1 or Area 46 injections, third-order neurons were found in the external segment of the globus pallidus (GPe), striatum and subthalamic nucleus (STN). In each of these nuclei, the third-order neurons that innervate M1 were spatially separated from those that innervate Area 46. Thus, distinct basal ganglia-thalamocortical circuits innervate M1 and Area 46. Next, we injected a conventional tracer into M1 to define its terminations in the putamen and STN. We found that the regions of the putamen and STN that receive input from M1 are the same as those that contain third-order neurons after M1 injections of virus. On the other hand, virus injections into M1 also labeled a relatively dense group of third-order neurons in a region of the ventral putamen that is not innervated by M1. This region of the putamen is the target of efferents from the amygdala. Thus, the ventral putamen may provide a route for the limbic system to influence motor output. Overall, our results indicate that basal ganglia circuits with the cerebral cortex can be characterized by both open- and closed-loop macro-architectures.