Synaptic transmission at central synapses has usually short latency and graded amplitude, thereby regulating threshold crossing and the probability of action potential generation. In the granular layer 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 vestibulo-cerebellum, we found that mossy fiber bundle stimulation also evoked (in ~80% of cases) a late-onset burst (after tens to hundreds milliseconds) independent from EPSP generation. Different 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, the late-onset response was insensitive to APV, NBQX and MCPG perfusion and did not therefore depend on conventional glutamatergic transmission mechanisms. The late-onset response was 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 Ca2+-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 modality of synaptic transmission may play an important role for regulating UBC activation and granular layer functions in the vestibulo-cerebellum

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

LOCATELLI, FRANCESCA;PRESTORI, FRANCESCA;MASETTO, SERGIO;D'ANGELO, EGIDIO UGO
2013-01-01

Abstract

Synaptic transmission at central synapses has usually short latency and graded amplitude, thereby regulating threshold crossing and the probability of action potential generation. In the granular layer 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 vestibulo-cerebellum, we found that mossy fiber bundle stimulation also evoked (in ~80% of cases) a late-onset burst (after tens to hundreds milliseconds) independent from EPSP generation. Different 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, the late-onset response was insensitive to APV, NBQX and MCPG perfusion and did not therefore depend on conventional glutamatergic transmission mechanisms. The late-onset response was 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 Ca2+-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 modality of synaptic transmission may play an important role for regulating UBC activation and granular layer functions in the vestibulo-cerebellum
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/632414
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