Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells

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Abstract

Unipolar Brush Cells (UBCs) have been suggested to play a critical role in cerebellar functioning, yet the corresponding cellular mechanisms remain poorly understood. UBCs have recently been reported to generate, in addition to early-onset glutamate receptor-dependent synaptic responses, a late-onset response (LOR) composed of a slow depolarizing ramp followed by a spike burst (Locatelli et al., 2013). The LOR activates as a consequence of synaptic activity and involves an intracellular cascade modulating H- and TRP-current gating. In order to assess the LOR mechanisms, we have developed a UBC multi-compartmental model (including soma, dendrite, initial segment, and axon) incorporating biologically realistic representations of ionic currents and a cytoplasmic coupling mechanism regulating TRP and H channel gating. The model finely reproduced UBC responses to current injection, including a burst triggered by a low-threshold spike (LTS) sustained by CaLVA currents, a persistent discharge sustained by CaHVA currents, and a rebound burst following hyperpolarization sustained by H- and CaLVA-currents. Moreover, the model predicted that H- and TRP-current regulation was necessary and sufficient to generate the LOR and its dependence on the intensity and duration of mossy fiber activity. Therefore, the model showed that, using a basic set of ionic channels, UBCs generate a rich repertoire of bursts, which could effectively implement tunable delay-lines in the local microcircuit. © 2014 Subramaniyam, Solinas, Perin, Locatelli, Masetto and D'Angelo.

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Subramaniyam, S., Solinas, S., Perin, P., Locatelli, F., Masetto, S., & D’Angelo, E. (2014). Computational modeling predicts the ionic mechanism of late-onset responses in unipolar brush cells. Frontiers in Cellular Neuroscience, 8(AUG). https://doi.org/10.3389/fncel.2014.00237

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