Late‐onset bursts evoked by mossy fibre bundle stimulation in unipolar brush cells: evidence for the involvement of H‐ and TRP‐currents
Authors: Locatelli F. , Bottà L. , Prestori F. , Masetto S. , D’Angelo E. 
Published: November 2012

Key points

Unipolar brush cells (UBCs) are specifically located in the vestibulo‐cerebellum and are considered to play an important role in implementing a ‘velocity storage’ system. Nonetheless, their synaptic and excitable mechanisms are not fully understood.

UBCs receive a giant synapse from a single mossy fibre generating a stereotyped excitatory postsynaptic potential (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 fibre bundle stimulation also evoked (in ∼80% of cases) a late‐onset burst (after tens to hundreds of milliseconds) independent of EPSP generation.

The late‐onset burst delay decreased and its duration increased by raising stimulation intensity or the number of impulses. The late‐onset burst was initiated by a slow depolarizing ramp driven by activation of an H‐current (sensitive to ZD7288 and Cs+) and of a TRP‐ (transient receptor potential) current (sensitive to SKF96365) and 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.

Through the late‐onset response, UBCs can translate the intensity of the input (coded as the number of active fibres and duration of their discharge) into output bursts with different delays. This time code could reverberate through the network along the chains made by UBCs with other UBCs and granule cells and may play an important role in regulating vestibulo‐cerebellum functions.

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 the vestibulo‐cerebellum, unipolar brush cells (UBCs) receive a giant synapse generating a stereotyped excitatory postsynaptic potential (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 fibre bundle stimulation also evoked (in ∼80% of cases) a late‐onset burst (after tens to hundreds of milliseconds) independent of 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. Although depending on synaptic activity, the late‐onset response was insensitive to perfusion of APV ((2R)‐5‐amino‐phosphonopentanoate), NBQX (2,3‐dioxo‐6‐nitro‐tetrahydrobenzo(f)quinoxaline‐7‐sulfonamide) and MCPG ((RS)‐α‐methyl‐4‐carboxyphenylglycine) 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‐ (transient receptor potential) current (sensitive to SKF96365), while the high voltage‐activated and high voltage‐activated Ca2+ currents (sensitive to nimodipine and mibefradil, respectively) 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 in regulating UBC activation and granular layer functions in the vestibulo‐cerebellum.