The cerebellum and basal ganglia are interconnected

Abstract

The cerebellum and the basal ganglia are major subcortical nuclei that control multiple aspects of behavior largely through their interactions with the cerebral cortex. Discrete multisynaptic loops connect both the cerebellum and the basal ganglia with multiple areas of the cerebral cortex. Interactions between these loops have traditionally been thought to occur mainly at the level of the cerebral cortex. Here, we review a series of recent anatomical studies in nonhuman primates that challenge this perspective. We show that the anatomical substrate exists for substantial interactions between the cerebellum and the basal ganglia. Furthermore, we discuss how these pathways may provide a useful framework for understanding cerebellar contributions to the manifestation of two prototypical basal ganglia disorders, Parkinson's disease and dystonia.

Fig. 1

Experimental paradigms and circuits interconnecting the cerebellum and basal ganglia: The left panel depicts the experimental paradigm and results from Hoshi et al. 2005, describing cerebellar output to the basal ganglia (orange circuit). We injected rabies virus into the striatum. The virus went through two stages of transport: retrograde transport to first-order neurons in the thalamus that innervate the injection site and then, retrograde transneuronal transport to second order neurons in the dentate nucleus (DN) that innervate the first-order neurons. Striatal neurons that receive cerebellar inputs include neurons in the “indirect” pathway that send projections to the external globus pallidus (GPe). The right panel of the figure depicts the experimental paradigm and results from Bostan et al. 2010, describing basal ganglia output to the cerebellum (purple circuit). We injected rabies virus into the cerebellar cortex. The virus went through two stages of transport: retrograde transport to first-order neurons in the pontine nuclei (PN) that innervate the injection site and then, retrograde transneuronal transport to second-order neurons in the subthalamic nucleus (STN) that innervate the first-order neurons. These interconnections enable two-way communication between the basal ganglia and the cerebellum. Each of these subcortical structures has separate parallel interconnections with the cerebral cortex (up and down large black arrows). The small black arrows in both panels indicate the direction of virus transport. DN: dentate nucleus; GPe: external segment of the globus pallidus; GPi: internal segment of the globus pallidus; PN: pontine nuclei; STN: subthalamic nucleus

Fig. 2

Dentate nucleus projection to the external segment of the globus pallidus: The left panel shows selected cross-sections of the dentate nucleus. Dots represent the location of third-order neurons labeled by retrograde transneuronal transport of rabies virus from the external segment of the globus pallidus. Black arrows indicate the level of the horizontal line through the middle of the dentate in the middle and right panels. The middle panel shows the distribution of labeled neurons on an unfolded map of the dentate. The arrows at the top of the map indicate the locations of slices in the left panel. The vertical dashed line marks the rostro-caudal center of the nucleus. Filled squares indicate the density of labeled neurons found in 200 μm×200 μm bins through the nucleus. The right panel shows the motor and nonmotor domains of the dentate. This map shows the origin of dentate projections to different cortical areas (M1 face, M1 arm, M1 leg: face, arm and leg representations in primary motor cortex; PMv arm: arm representation in the ventral premotor area; SMA arm: arm representation in the supplementary motor area; 7b: area 7b in the posterior parietal cortex; FEF: frontal eye fields; pre-SMA: pre-supplementary motor area; 9, 46d: areas 9 and dorsal area 46 in the prefrontal cortex). The curved dotted line indicates the border between motor and nonmotor domains of the dentate. The vertical dashed line marks the rostro-caudal center of the nucleus. C: caudal; D: dorsal. (The left and middle panels of this figure are from Hoshi et al. 2005; the right panel is modified from Hoshi et al. 2005 to include additional data, see Strick et al. 2009)

Fig. 3

STN projection to the cerebellar hemisphere: a Histogram of the rostro-caudal distribution of second-order neurons labeled in the STN by retrograde transport of virus from Crus IIp (red bars) and HVIIB (blue bars). Missing bars correspond to missing sections. b Charts of labeled neurons in STN after rabies virus injections into Crus IIp (red dots) and HVIIB (blue dots) are overlapped to illustrate the topographic differences in distribution of STN second-order neurons in the two cases. c Schematic representation of STN organization, according to the tripartite functional subdivisions of the basal ganglia (Parent and Hazrati 1995b; Joel and Weiner 1997; Hamani et al. 2004). d Schematic summary of the known connections between STN and areas of the cerebral cortex. C: caudal; D: dorsal; M: medial; STN: subthalamic nucleus. (Figure from Bostan et al. 2010)