Skip to main content

Advertisement

The mechanisms of late-onset synaptic responses in a realistic model of Unipolar Brush Cells

Article metrics

  • 662 Accesses

  • 1 Citations

Unipolar brush cells (UBCs) are excitatory glutamatergic interneurons of the cerebellar granular layer receiving both primary and secondary vestibular inputs through mossy fibers (excitatory input) and Golgi cell axon (inhibitory input). When injected with progressively increasing depolarizing currents from a negative membrane potential, the UBC generates a burst sustained by a calcium spike and then a protracted discharge with shorter latency and spike frequency adaptation. The intrinsic excitability of UBCs is determined by an H current and by Low Voltage activated and High Voltage activated calcium currents [2, 3]. Fast inactivating T-type Calcium channels generate low-threshold spikes and L-type Calcium channel sustain tonic firing. The H current (activated between -60 mV and -80 mV) produces a slow hyperpolarization characterized by a "sag" in response to a hyperpolarizing step and an afterhyperpolarization at the end of a depolarizing step. Here we present a biologically realistic multi-compartmental mathematical model of the UBC realized with the NEURON-PYTHON simulator. According to literature [14], ionic channels are distributed among compartments (soma, dendrite, initial segment and axon). The model can reproduce the excitable properties of UBCs in current-clamp and voltage-clamp modes. The response to mossy fiber inputs was reproduced using synaptic models of AMPA and NMDA synaptic receptors. The model is also capable of reproducing the late onset response recently reported for this cellular type [5] by exploiting the interaction between cAMP, TRPC, and H current. This model, in addition to confirm the primary role of the aforementioned currents in UBC's electroresponsiveness, will prove a valuable tool for investigating the UBC's function in the cerebellar network.

References

  1. 1.

    Rossi DJ, Alford S, Mugnaini E, Slater NT: Properties of transmission at a giant glutamatergic synapse in cerebellum: the mossy fiber-unipolar brush cell synapse. Journal of neurophysiology. 1995, 74 (1): 24-42.

  2. 2.

    Diana MA, Otsu Y, Maton G, Collin T, Chat M, Dieudonné S: T-type and L-type Ca2+ conductances define and encode the bimodal firing pattern of vestibulocerebellar unipolar brush cells. J Neurosci. 2007, 27 (14): 3823-3838. 10.1523/JNEUROSCI.4719-06.2007.

  3. 3.

    Russo MJ, Yau HJ, Nunzu MG, Mugnaini E, Martina M: Dynamic metabotropic control of intrinsic fring in cerebellar unipolar brush cells. J Neurophysiol. 2008, 100 (6): 3351-3360. 10.1152/jn.90533.2008.

  4. 4.

    Ruigrok TJH, Hensbroek RA, Simpson JI: Spontaneous activity signatures of morphologically identified interneurons in the vestibulocerebellum. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2011, 31: 712-24. 10.1523/JNEUROSCI.1959-10.2011.

  5. 5.

    Locatelli F, Bottà L, Prestori F, Masetto S, D'Angelo E: Late-onset bursts evoked by mossy fiber bundle stimulation in unipolar brush cells: evidence for the involvement of H- and TRP-currents. The Journal of physiology. 2012, 1-23.

Download references

Acknowledgements

This work was supported by the EU projects CEREBNET and REALNET to ED and by grants of the Italian Ministry of Health to ED (RF-2009-1475845) and to S Solinas (GR-2009-1493804). S Subramaniyam is recipient of a grant from CEREBNET.

Author information

Correspondence to Egidio D'Angelo.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Subramaniyam, S., Perin, P., Locatelli, F. et al. The mechanisms of late-onset synaptic responses in a realistic model of Unipolar Brush Cells. BMC Neurosci 14, P79 (2013) doi:10.1186/1471-2202-14-S1-P79

Download citation

Keywords

  • Mossy Fiber
  • Golgi Cell
  • Spike Frequency Adaptation
  • Negative Membrane Potential
  • Intrinsic Excitability