Abstract
In the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. Yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. Here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (STN) and the cerebellar cortex as has been demonstrated earlier for the primate. A mixture of unmodified rabies virus (RABV: CVS 11) and cholera toxin B-subunit (CTb) was injected at places in the posterior cerebellar cortex of nine rats. The survival time was chosen to allow for disynaptic retrograde transneuronal infection of RABV. We examined the STN for neurons infected with RABV in all nine cases and related the results with the location of the RABV/CTb injection site, which ranged from the vermis of lobule VII, to the paravermis and hemispheres of the paramedian lobule and crus 2a. We found that cases with injection sites in the vermis of lobule VII showed prominent RABV labeling in the STN. In contrast, almost no subthalamic labeling was noted in cases with paravermal or hemispheral injection sites. We show circumstantial evidence that not only the pontine nuclei but also the pedunculotegmental nucleus may act as the intermediary in the connection from STN to cerebellar cortex. This finding implies that in the rat the STN links disynaptically to the vermal part of lobule VII of the cerebellar cortex, without any major involvement of the cerebellar areas that are linked to sensorimotor functions. As vermal lobule VII recently has been shown to process disynaptic input from the retrosplenial and orbitofrontal cortices, we hypothesize that in the rat the subthalamic input to cerebellar function might be used to influence more prominently non-motor functions of the cerebellum than motor functions. This latter aspect seems to contradict the primate results and could point to a more elaborate interaction between basal ganglia and cerebellum in more demanding motor tasks.
Highlights
The basal ganglia and the cerebellum are major subcortical brain structures that control mainly motor, and non-motor aspects of behavior initiated by the cerebral cortex (Gold et al, 1989; Middleton and Strick, 2000; Schmahmann and Caplan, 2006; Strick et al, 2009; D’Angelo and Casali, 2012; Schultz, 2016)
A total of nine injections with a mixture of rabies virus (RABV) and cholera toxin B-subunit (CTb) into lobule VII were evaluated for the present study
Retrograde, i.e., somatic, labeling of neurons outside of the cerebellum was carefully evaluated in both CTb- and RABV-processed sections
Summary
The basal ganglia and the cerebellum are major subcortical brain structures that control mainly motor, and non-motor aspects of behavior initiated by the cerebral cortex (Gold et al, 1989; Middleton and Strick, 2000; Schmahmann and Caplan, 2006; Strick et al, 2009; D’Angelo and Casali, 2012; Schultz, 2016). The use of transneuronal tracers has shown the existence of subcortical disynaptic connections between the basal ganglia and the cerebellum (Bostan et al, 2010). Imaging studies that use diffusion magnetic resonance imaging and tractography have shown that this disynaptic connection between the STN and the cerebellar cortex may be present in the human brain (Pelzer et al, 2013; Milardi et al, 2016). As such, these findings provide neuroanatomical evidence for the putative role of an affected interplay between basal ganglia and cerebellum in movement disorders. This has been largely derived from clinical and animal studies that showed a cerebellar component in disorders typically associated with basal ganglia dysfunction like Parkinson disease (especially in the generation of rest tremors; Benabid et al, 1991; Rascol et al, 1997; Wu and Hallett, 2005, 2013) or dystonia (Chen et al, 2014)
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