Cerebellar granular layer contains, in addition to granule and Golgi cells, the unipolar brush cells (UBCs). Although several works revealing the basic synaptic and excitable properties of UBCs (Rossi et al., 1995; Diana et al., 2007), synaptic activation mechanisms remained poorly understood. By using patch-clamp recordings in rat vestibulo-cerebellar slices (P17-P24; n=160), we found that mossy fiber (MF) stimulation also evoked (~70% of cases) a late-onset burst (tens to hundreds of milliseconds) independent from previous EPSP generation. This burst delay decreased, its duration increased by raising MF stimulation intensity and was initiated by a slow depolarizing ramp, driven by activation of a ZD7288- and Cs+-sensitive H-current (Ih). The effect was reinforced by a cooperative contribution from TRP channels and was occluded by cAMP.

After perfusion of 2 mM ZD 7288, the slope of the depolarizing ramp leading to the late-onset burst decreased resulting in a significant increase of the burst delay (65,32%± 41,92%; p<0.1). The increase of inward currents by MF stimulation was significantly reduced by intracellular perfusion of 500 mM cAMP through the patch pipette: from 29.3±5.3% to 8.6±3.3% at the end of current step; p<0.01.

These results indicate that MF activity can regulate Ih gating through a yet unknown neuromodulator mechanism. This novel modality of UBC activation may play an important role for regulating granular layer functions in the vestibulo-cerebellum.