Late-onset bursts evoked by mossy fiber bundle stimulation in unipolar brush cells: evidence for the involvement of H-and TRP-currents

20) Francesca Locatelli Post doc University of Pavia francesca.locatelli@unipv.it Late-onset bursts evoked by mossy fiber bundle stim ulation in unipolar brush cells: evidence for the involvement of H- and TRP-currents Francesca Locatelli 1 , Luisa Bottà 1 , Francesca Prestori 1 , Sergio Masetto 1 , Egidio D’Angelo 1,2 1 Department of Neuroscience, University of Pavia, I taly 2 Brain Connectivity Center (BCC), IRCCS C. Mondino, Pavia, Italy Synaptic transmission at central synapses has usual ly short latency and graded amplitude, thereby regulating threshold crossing and the probability o f action potential generation. In the granular laye r of vestibulo-cerebellum, the unipolar brush cells ( UBCs) receive a giant synapse generating a stereotyped EPSP-burst complex with early-onset (~ 2 ms) and high reliability. By using patch- clamp recordings in cerebellar slices of the rat ve stibulo-cerebellum, we found that mossy fiber bundle stimulation also evoked (in ~85% of cases) a late-onset burst (after tens to hundreds milliseconds) independent from EPSP generation. Dif ferent from the early-onset, the late-onset burst delay decreased and its duration increased by raising stimulation intensity or the number of impulses. Though depending on synaptic activity, th e late-onset response was insensitive to APV, NBQX and MCPG perfusion and did not therefore depen d on conventional glutamatergic transmission mechanisms. The late-onset response wa s initiated by a slow depolarizing ramp driven by activation of an H-current (sensitive to ZD7288- and Cs + ) and of a TRP-current (sensitive to SKF96365), while the HVA and LVA Ca 2+ -currents (sensitive to nimodipine and mibefradil) played a negligible role. The late-onset burst was occluded by intracellular cAMP. These results indicate that afferent activity can regulate H- and TRP-current gating in UBCs generating synaptically-driven EPSP-independent responses, in which the delay rather than amplitude is graded with the intensity of the input pattern. This modal ity of synaptic transmission may play an important role for regulating UBC activation and gr anular layer functions in the vestibulo- cerebellum.