The unipolar brush cell: A remarkable neuron finally receiving deserved attention

Abstract

Unipolar brush cells (UBC) are small, glutamatergic neurons residing in the granular layer of the cerebellar cortex and the granule cell domain of the cochlear nuclear complex. Recent studies indicate that this neuronal class consists of three or more subsets characterized by distinct chemical phenotypes, as well as by intrinsic properties that may shape their synaptic responses and firing patterns. Yet, all UBCs have a unique morphology, as both the dendritic brush and the large endings of the axonal branches participate in the formation of glomeruli. Although UBCs and granule cells may share the same excitatory and inhibitory inputs, the two cell types are distinctively differentiated. Typically, whereas the granule cell has 4-5 dendrites that are innervated by different mossy fibers, and an axon that divides only once to form parallel fibers after ascending to the molecular layer, the UBC has but one short dendrite whose brush engages in synaptic contact with a single mossy fiber terminal, and an axon that branches locally in the granular layer; branches of UBC axons form a non-canonical, cortex-intrinsic category of mossy fibers synapsing with granule cells and other UBCs. This is thought to generate a feed-forward amplification of single mossy fiber afferent signals that would reach the overlying Purkinje cells via ascending granule cell axons and their parallel fibers.In sharp contrast to other classes of cerebellar neurons, UBCs are not distributed homogeneously across cerebellar lobules, and subsets of UBCs also show different, albeit overlapping, distributions. UBCs are conspicuously rare in the expansive lateral cerebellar areas targeted by the cortico-ponto-cerebellar pathway, while they are a constant component of the vermis and the flocculonodular lobe. The presence of UBCs in cerebellar regions involved in the sensorimotor processes that regulate body, head and eye position, as well as in regions of the cochlear nucleus that process sensorimotor information suggests a key role in these critical functions; it also invites further efforts to clarify the cellular biology of the UBCs and their specific functions in the neuronal microcircuits in which they are embedded. High density of UBCs in specific regions of the cerebellar cortex is a feature largely conserved across mammals and suggests an involvement of these neurons in fundamental aspects of the input/output organization as well as in clinical manifestation of focal cerebellar disease.

Variable timing of synaptic transmission in cerebellar unipolar brush cells

“…UBCs thus form an intricate network of excitatory feedforward projections within the granular layer, and it has been estimated that in the nodulus at least 50% of mossy fiber terminals arise from UBCs (12). The peculiar specialization of the synapse, in combination with the strategic position in the granular layer network, is likely to allow UBCs to importantly influence cortical information processing (13,14).…”

Mixed Inhibitory Synaptic Balance Correlates with Glutamatergic Synaptic Phenotype in Cerebellar Unipolar Brush Cells

“…and S.D., unpublished results) suggests that these cells operate mostly as integrators and/or temporal filters. Distinct integrative modalities of UBCs are likely to be determined by the heterogeneous expression of receptors at the MF synapse (Mugnaini et al, 2011). Preliminary experiments (M.A.D.…”

Commentary on “E. Mugnaini and A. Floris, The Unipolar Brush Cell: A Neglected Neuron of the Mammalian Cerebellar Cortex. J Comp Neurol, 339:174–180, 1994”

“…Taken together, these results suggest that this intrinsic network of UBC axons generate a feed-forward amplification of single mossy fiber afferent signals that would reach the overlying Purkinje cells via ascending granule cell axons and their parallel fibers [18]. These finding also require that Fig.…”