The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and cerebellar loops have been assumed to be anatomically separate and to perform distinct functional operations. We investigated whether there is any direct route for basal ganglia output to influence cerebellar function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence cerebellar function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated functional network. cerebellar cortex | subthalamic nucleus | virus tracing T he basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect (1, 2). Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. The major interactions between these loops were thought to occur largely at the cortical level (3). Recently, we showed that one of the output nuclei of the cerebellum, the dentate nucleus, has a disynaptic projection to an input stage of basal ganglia processing, the striatum (4). This pathway enables cerebellar output to influence basal ganglia function. Here, we investigated whether a comparable pathway allows basal ganglia output to influence cerebellar function. We injected rabies virus (RV) into regions of the cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. Our results indicate that the subthalamic nucleus (STN) of the basal ganglia has substantial disynaptic projections to the cerebellar cortex. ResultsWe injected the N2c strain of RV into selected sites within the cerebellar cortex of three cebus monkeys ( Fig. 1 and Table S1). RV is transported transneuronally in the retrograde direction in a time-dependent fashion in nonhuman primates (4-8). We set the survival time at 42 h to allow two stages of transport: retrograde transport of RV to first-order neurons that project to the injection site and th...

The dominant view of cerebellar function has been that it is exclusively concerned with motor control and coordination. Recent results from neuroanatomical, behavioral and imaging studies have profoundly changed this view. Neuroanatomical studies using virus transneuronal tracers have demonstrated that the output from the cerebellum reaches vast areas of the neocortex, including regions of prefrontal and posterior parietal cortex. Furthermore, it has recently become clear that the cerebellum is reciprocally connected with the basal ganglia, indicating that the two subcortical structures are part of a densely interconnected network. Altogether, these results provide the neuroanatomical substrate for cerebellar involvement in non-motor functions mediated by the prefrontal and posterior parietal cortex, as well as in processes traditionally associated with the basal ganglia.

The basal ganglia and the cerebellum are considered to be distinct subcortical systems that perform unique functional operations. The outputs of the basal ganglia and the cerebellum influence many of the same cortical areas but do so by projecting to distinct thalamic nuclei. As a consequence, the two subcortical systems were thought to be independent and to communicate only at the level of the cerebral cortex. Here, we review recent data showing that the basal ganglia and the cerebellum are interconnected at the subcortical level. The subthalamic nucleus in the basal ganglia is the source of a dense disynaptic projection to the cerebellar cortex. Similarly, the dentate nucleus in the cerebellum is the source of a dense disynaptic projection to the striatum. These observations lead to a new functional perspective that the basal ganglia, the cerebellum and the cerebral cortex form an integrated network. This network is topographically organized so that the motor, cognitive and affective territories of each node in the network are interconnected. This perspective explains how synaptic modifications or abnormal activity at one node can have network-wide effects. A future challenge is to define how the unique learning mechanisms at each network node interact to improve performance.