期刊
FRONTIERS IN CELLULAR NEUROSCIENCE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2014.00237
关键词
biorealistic modeling; unipolar brush cells; vestibular cerebellum; slow synaptic responses; ionic channel regulation
资金
- European Union to Egidio D'Angelo (CEREBNET) [CEREBNET FP7-ITN238686, REALNET FP7-ICT270434]
- Human Brain Project [HBP-604102]
- Italian Ministry of Health [RF-2009-1475845, GR-2009-143804]
- ISCRA grant [IsA07]
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 (Locate 111 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.
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