Skip to main content

Advertisement

Modeling the excitability of the cerebellar Purkinje cell with detailed calcium dynamics

Article metrics

  • 1038 Accesses

  • 1 Citations

Previous studies have suggested that the activity pattern of a cerebellar Purkinje cells (PC) is significantly controlled by voltage activated Ca2+ channels and Ca2+ activated K+ channels, present mainly on its elaborate dendritic tree [1]. Although the main somatic excitatory drive propagates very weakly into the dendritic tree [2], somehow a significant interaction between somatic and dendritic spiking occurs. Ca2+ entering through P-type channel is thought to be the main source of this excitability modulation, and this Ca2+ influx also activates large conductance (BK) and small conductance (SK) Ca2+ dependent K+ channels [1, 3]. This interaction often results in the counter-intuitive computational somatic and dendritic spiking behavior of PCs [4], but nevertheless this important aspect has not been thoroughly investigated in previous computational modeling studies.

In this work, we try to integrate known aspects of Ca2+ dynamics in PC dendrites by building a new model, which would help us understand the consequent computational properties of a PC. Recently, it has been shown that BK channels are in close vicinity of Ca2+ sources as compared to SK channels [5], suggesting that BK channels require a brief large amount (~10–100 μM) of Ca2+ whereas SK channels require a long yet small quantity (~0.1–2 μM) of Ca2+ for the activation. Therefore it might be interesting to see how this spatiotemporal interaction of Ca2+ sources with Ca2+ activated K+ channels takes place in simulation. Due to lack of sufficient experimental data about the interaction between Ca2+ sources and Ca2+ activated channels in PCs, we could only capture temporal interaction by including Ca2+ dynamics with several buffers and pumps [6] in our model. We expect that this will be sufficient to activate the BK and SK channel correctly. In addition to introducing complex Ca2+ dynamics to our model, we also built new kinetic models of the P-type Ca2+ channel and BK channel based on the recent experimental data [7] and gating kinetics with both voltage and Ca2+ dependence [8].

Not only the composition of active ionic mechanisms, the dendritic morphology can also significantly modify the spiking pattern [9]. However, simulation on the detailed reconstructed morphology of a PC dendritic tree is not suitably efficient for parameter tuning to obtain a desired behavior. Therefore, to investigate the morphological significance in firing behaviors, we have built and used an electrotonically accurate reduced morphology of a PC as well as an even simpler three-compartment model comprising of soma, smooth dendrite and spiny dendrite.

References

  1. 1.

    Edgerton JR, Reinhart PH: Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J Physiol. 2003, 548: 53-69. 10.1113/jphysiol.2002.027854.

  2. 2.

    Vetter P, Roth A, Häusser M: Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol. 2001, 85: 926-937.

  3. 3.

    Womack MD, Khodakhah K: Somatic and dendritic small-conductance calcium-activated potassium channels regulate the output of cerebellar purkinje neurons. J Neurosci. 2003, 23: 2600-2607.

  4. 4.

    Davie JT, Clark BA, Hausser M: The origin of complex spike in cerebellar Purkinje cells. J Neurosci. 2008, 28: 7599-7609. 10.1523/JNEUROSCI.0559-08.2008.

  5. 5.

    Fakler B, Adelman JP: Control of KCa channels by calcium nano/microdomains. Neuron. 2008, 59: 873-881. 10.1016/j.neuron.2008.09.001.

  6. 6.

    Schmidt H, Stiefel KM, Racay P, Schwaller B, Eilers J: Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k. J Physiol. 2003, 551: 13-32. 10.1113/jphysiol.2002.035824.

  7. 7.

    Sun XP, Yazejian B, Grinnell AD: Electrophysiological properties of BK channels in Xenopus motor nerve terminals. J Physiol. 2004, 557: 207-228. 10.1113/jphysiol.2003.060509.

  8. 8.

    Moczydlowski E, Latorre R: Gating Kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. J Gen Physiol. 1983, 82: 511-542. 10.1085/jgp.82.4.511.

  9. 9.

    Mainen ZF, Sejnowski TJ: Influence of dendritic structure on firing pattern in model neocortical neurons. Nature. 1996, 382: 363-366. 10.1038/382363a0.

Download references

Author information

Correspondence to Haroon Anwar.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Keywords

  • Purkinje Cell
  • Dendritic Tree
  • Cerebellar Purkinje Cell
  • Purkinje Cell Dendrite
  • Reconstructed Morphology