Cerebellar Cortical and Corticonuclear Circuitry

Climbing fibers (CFs) arise exclusively from the inferior olive. Axons of olivary neurons branch to form 7 to 10 CFs. Each CF provides extensive excitatory synaptic contact with the dendritic tree of a single PC (between 1,000 and 1,500 synaptic contacts between a CF and its PC). Climbing fibers enter the cerebellum through the inferior cerebellar peduncle (ICP), branch in the white matter, where they emit collaterals to the deep cerebellar nuclei (DCN), and ascend to the molecular layer. In the lower two thirds of the molecular layer the CF is tightly wound around the trunk and major proximal branches of the PC dendritic tree. Each varicosity of a CF synapses with several dendritic spines arising from the same dendritic branch. Fine tendrils that branch off from the CF in the molecular layer synapse with ascending branches of the basket cell axon and with the dendritic trees of stellate and Golgi cells. The olivocerebellar projection is organized according to a strict mediolateral parasagittal zonal pattern (see Plate 8-12).

Mossy fibers (MFs) are named for their thickened terminals that have thick, short, divergent, varicose branches resembling moss. Their synaptic arborizations are termed rosettes, have a variety of shapes, and are located along the course of the MF in the granular layer at the branch points and at their sites of terminations. MFs are heavily myelinated and convey excitatory afferents to the cerebellar cortex from the spinal cord, brainstem (except the olive), and the cerebral hemispheres. They enter through all three cerebellar peduncles, giving off 20 to 30 collateral branches in the white matter of the folium as they course toward the granular layer. They also provide collaterals to the deep cerebellar nuclei. Many MFs terminate bilaterally in the cerebellum after crossing in the cerebellar white matter. Unlike the CF, the MF provides excitatory input to the PC indirectly. The MF rosette is the central component of the granule cell glomerulus, the complex articulation between MF rosettes and the terminal arborizations of granule cell dendrites. Each MF rosette makes excitatory synaptic contact with 50 to 100 dendritic terminals from up to 20 granule cells and receives inhibitory feedback from the descending axons of Golgi cells. The granule cell axon ascends toward the molecular layer, making synaptic contact with dendrites of Golgi cells in the granular layer and spines of the proximal dendrites of PCs in the molecular layer. Upon reaching the molecular layer, the granule cell axon divides to form parallel fibers (PFs), the two branches traveling in opposite directions along the folium. The PFs make synaptic contact with one or two spiny branchlets on intermediate and distal regions of the dendritic trees of up to 300 PCs along the folium.

Each PC receives synaptic inputs from approximately 200,000 parallel fibers. In addition to excitatory inputs to the PCs from MFs and CFs, the PCs participate in a bidirectional corticonuclear projection, receiving excitatory feedback back from those regions of the DCN and vestibular nuclei to which the PC inhibitory projection is directed. The PCs receive inhibitory inputs from interneurons in the molecular layer—stellate cells, basket cells, and Lugaro cells, all of which receive excitatory afferents from the ascending granule cell axon and the PFs. Recurrent axon collaterals of the PCs are also inhibitory. The dendrites of the unipolar brush cell (UBC) in the vestibulocerebellum, the only excitatory cerebellar interneuron, receive MF inputs within the granule cell glomerulus. The net effect of these finely balanced interactions is that inputs to cerebellum are excitatory, output from the cortex via the PC is inhibitory, and output from the cerebellum via the DCN is excitatory to thalamus and brainstem but inhibitory to the inferior olive.

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