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Modeling the excitability of the cerebellar Purkinje cell with detailed calcium dynamics
BMC Neuroscience volume 10, Article number: P34 (2009)
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 . Although the main somatic excitatory drive propagates very weakly into the dendritic tree , 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 , 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 , 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  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  and gating kinetics with both voltage and Ca2+ dependence .
Not only the composition of active ionic mechanisms, the dendritic morphology can also significantly modify the spiking pattern . 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.
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.
Vetter P, Roth A, Häusser M: Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol. 2001, 85: 926-937.
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.
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.
Fakler B, Adelman JP: Control of KCa channels by calcium nano/microdomains. Neuron. 2008, 59: 873-881. 10.1016/j.neuron.2008.09.001.
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.
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.
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.
Mainen ZF, Sejnowski TJ: Influence of dendritic structure on firing pattern in model neocortical neurons. Nature. 1996, 382: 363-366. 10.1038/382363a0.
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Anwar, H., Hong, S. & De Schutter, E. Modeling the excitability of the cerebellar Purkinje cell with detailed calcium dynamics. BMC Neurosci 10, P34 (2009). https://doi.org/10.1186/1471-2202-10-S1-P34
- Purkinje Cell
- Dendritic Tree
- Cerebellar Purkinje Cell
- Purkinje Cell Dendrite
- Reconstructed Morphology