What Is the Role of the Dentate Nucleus in Normal and Abnormal Cerebellar Function?

Abstract

The cerebellum participates in motor, cognitive, and behavioral control through parallel cortico-cerebello-thalamocortical loops.1-5 Cerebellar function is shaped by the activity of Purkinje cells, which integrate inputs conveyed through the mossy-parallel and climbing fiber systems and tonically control the activity of the cerebellar nuclei.6-9 The dentate nucleus (DN) receives the majority of afferents from the cerebellar cortex and provides the excitatory output of the cerebellum to the thalamus and brainstem6 (Figure). Functional neuroimaging and tractography studies indicate that the DN consists of different territories that are functionally connected to several cortical networks.10-16 The DN also has a major role in the interactions between the cerebellum and the basal ganglia.17-20 The DN, like other cerebellar nuclei, also contains neurons that send an inhibitory projection to the inferior olive (IO) and control the synchronized oscillatory of its neurons, which regulate timing and plasticity in the cerebellum.21-24 Therefore, dysfunction of the DN, either due to its direct involvement by disease25 or secondary to aberrant firing of Purkinje cells,26 has a major role in a wide range of manifestations of cerebellar disorders including ataxia,4,5 tremor,27-30 and dystonia.31,32 The DN is therefore a target for deep brain stimulation (DBS).33-40 The functional connectivity of the DN with large scale cortical networks indicates its potential involvement in cognitive and affective manifestations of cerebellar and other disorders.3,16,41-44