Regulation of striatal cells and goal-directed behavior by cerebellar outputs

Abstract

The cerebellum integrates descending motor commands and sensory information to generate predictions and detect errors during ongoing behaviors. Cerebellar computation has been proposed to control motor but also non-motor behaviors, including reward expectation and cognitive flexibility. However, the organization and functional contribution of cerebellar output channels are incompletely understood. Here, we elaborate the cell-type specificity of a broad connectivity matrix from the deep cerebellar nuclei (DCN) to the dorsal striatum in mice. Cerebello-striatal connections arise from all deep cerebellar subnuclei and are relayed through intralaminar thalamic nuclei (ILN). In the dorsal striatum, these connections target medium spiny neurons, but also ChAT-positive interneurons, a class of tonically active interneurons implicated in shifting and updating behavioral strategies. Chemogenetic silencing of cerebello-striatal connectivity modifies function of striatal ChAT-positive interneurons. We propose that cerebello-striatal connections relay cerebellar computation to striatal circuits for goal-directed behaviors.

Modular output circuits of the fastigial nucleus mediate diverse motor and nonmotor functions of the cerebellar vermis

“…We did not observe significant labeling in the infralimbic, medial orbitofrontal, 287 retrosplenial, auditory or temporal cortical areas (Figure 6 -figure supplement 1). 288Disynaptic projections from the FN to subcortical forebrain regions were robust in the dorsal 289 striatum (Figures 6C,D,H), consistent with a recent study using rabies virus(Xiao et al, 2018), 290…”

Direct evidence for transport of RNA from the mouse brain to the germline and offspring

“…We used this gene fragment to determine presence of the virus. Despite the fact that the AAV1 virus can be retrogradely transported via axons to the contralateral region [27] and the cerebellum [28], this system allowed us to restrict viral infection to the target site, and to discrete regions of the mouse brain while then specifically monitoring potential transport of virally-expressed pre-MIR941-1 outside of the brain using gene-specific PCR.…”

A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

“…5j-l). The FN projects to a myriad of downstream targets that play various roles in both motor and non-motor functions [36][37][38][39][40][41] . In this study, we mainly focused on the FN-MdV pathway, yet it is possible that MdV-projecting FN neurons provide efference copies to many other brain regions by their collateral projections .…”

“…Vermal PCs project to the fastigial nucleus (FN), which targets vast numbers of downstream brain regions 34,35 . Indeed, FN outputs have recently been implied to play various roles in both motor and nonmotor tasks [36][37][38][39][40][41] . Anatomical studies using retrograde transneuronal tracing with rabies virus from the eyelid muscle (orbicularis oculi) have revealed prominent labeling in IN and FN, suggesting a potential role of the vermis and FN in controlling eyelid movements 42,43 .…”