Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes in mice. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.

Selective targeting of unipolar brush cell subtypes by cerebellar mossy fibers

In vestibular cerebellum, primary afferents carry signals from single vestibular end organs, whereas secondary afferents from vestibular nucleus carry integrated signals. Selective targeting of distinct mossy fibers to postsynaptic cells determines how the cerebellum processes vestibular signals. We focused on vestibular projections to ON and OFF classes of unipolar brush cells (UBCs), which transform single mossy fiber signals into long-lasting excitation or inhibition respectively, and impact the activity of ensembles of granule cells. To determine whether these contacts are indeed selective, connectivity was traced back from UBC to specific ganglion cell, hair cell and vestibular organ subtypes. We show that a specialized subset of primary afferents contacts ON UBCs, but not OFF UBCs, while secondary afferents contact both subtypes. Striking anatomical differences were observed between primary and secondary afferents, their synapses, and the UBCs they contact. Thus, each class of UBC functions to transform specific signals through distinct anatomical pathways.

NMDA Receptor-Mediated Currents in Rat Cerebellar Granule and Unipolar Brush Cells

The properties of N-methyl-d-aspartate (NMDA) receptor-mediated currents at the giant cerebellar mossy-fiber unipolar brush cell (UBC) synapse were compared with those of adjacent granule cells using patch-clamp recording methods in thin slices of rat cerebellar nodulus. In UBCs, NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) decayed as a single exponential whose time constant was independent of membrane potential. The EPSC was reduced in all cells by the NR1/NR2B-selective antagonist ifenprodil, and the Zn2+ chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) produced a transient potentiation in 50% of cells. In contrast, the NMDA EPSC in granule cells decayed as a double exponential that dramatically switched to a slower rate at positive membrane potentials. The synaptic response in some granule cells also displayed a late second peak at positive potentials, and in others, activation of mossy fibers produced repetitive trains of EPSCs indicating they may be postsynaptic to the UBC network. Single-channel recordings of outside-out somatic patches from UBCs in magnesium-free solution revealed only high-conductance (50 pS) channels whose open time was increased with depolarization, but the opening frequency was decreased to yield a low ( p o = 0.0298), voltage-independent opening probability. Lowering extracellular calcium (2.5–0.25 mM) had no effects on channel gating, although an increase of single-channel conductance was observed at lower calcium concentrations. Taken together, the data support the notion that the NMDA receptor in UBCs may comprise both NR1/NR2A and NR1/NR2B receptors. Furthermore, the properties of the EPSC in these two classes of feedforward glutamatergic interneurons display fundamental differences that may relate to their roles in synaptic integration.