Widespread inhibitory projections from the interposed cerebellar nucleus

The cerebellum consists of parallel parasagittal modules that contribute to diverse behaviors, spanning motor to cognitive. Recent work illustrating a role for the anterior interposed nucleus (IntA) in reach control in mice raised questions of its anatomical organization that could confer functional specificity. We employed intersectional cell- and projection- specific labeling methods to map IntA inputs and outputs. In contrast to long-standing dogma of primarily excitatory outputs and restricted inferior olive targeting inhibitory output, we found that inhibitory IntA neurons ramified widely within the brainstem, targeting both motor- and sensory-related nuclei, suggesting potential functional roles in disinhibitory control or predictive sensory cancellation. Using monosynaptic rabies tracing, we then found that excitatory output neurons receive fewer and more precisely organized inputs than inhibitory neurons, which may set them up for distinct computations. Together these data suggest IntA contains at least two distinct output circuits and promise advances in identifying parallel computations of the cerebellum.

Electrical stimulation of the lateral cerebellar nucleus promotes neurogenesis in rats after motor cortical ischemia

Deep brain stimulation (DBS) has been tentatively explored to promote motor recovery after stroke. Stroke could transiently activate endogenous self-repair processes, including neurogenesis in the subventricular zone (SVZ). In this regard, it is of considerable clinical interest to study whether DBS of the lateral cerebellar nucleus (LCN) could promote neurogenesis in the SVZ for functional recovery after stroke. In the present study, rats were trained on the pasta matrix reaching task and the ladder rung walking task before surgery. And then an electrode was implanted in the LCN following cortical ischemia induced by endothelin-1 injection. After 1 week of recovery, LCN DBS coupled with motor training for two weeks promoted motor function recovery, and reduced the infarct volumes post-ischemia. LCN DBS augmented poststroke neurogenetic responses, characterized by proliferation of neural progenitor cells (NPCs) and neuroblasts in the SVZ and subsequent differentiation into neurons in the ischemic penumbra at 21 days poststroke. DBS with the same stimulus parameters at 1 month after ischemia could also increase nascent neuroblasts in the SVZ and newly matured neurons in the perilesional cortex at 42 days poststroke. These results suggest that LCN DBS promotes endogenous neurogenesis for neurorestoration after cortical ischemia.