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De Schutter: Purkinje Cell Model


The cerebellar Purkinje cell is one of the largest and most complex neurons in the mammalian nervous system. Purkinje cells have very active dendrites, generating massive Ca2+ signals in response to synaptic input [1119]. Further, the unusual isoplanar anatomic organization of this cells dendrite has been conserved to a remarkable degree through evolution [5], suggesting that this specific morphology is essential to the function of the Purkinje cell.

In addition to its anatomic and physiological complexity and uniqueness, Purkinje cell activity also constitutes the sole output of the cerebellar cortex. Although the precise computational role of the cerebellum is not yet known, it is clear that understanding the physiology of the Purkinje cell will be an essential part in unraveling the function of the cerebellar cortex as a whole. Given the complexity of this cell, we believe that computer modeling techniques are necessary to explore and analyze completely the properties of Purkinje cells.

In this paper we describe a large, detailed compartmental model [131415] of the Purkinje cell based on real Purkinje cell morphology, which includes 10 active voltage-dependent ionic conductances that have so far been demonstrated to exist in these neurons. Model parameters were established using the results of several recent voltage-clamp studies of conductances in Purkinje cells [3461720]. We tested whether the model was robust to changes in the densities of individual channels. The model was then used to explore the ionic mechanisms underlying the complex response properties of Purkinje cells to current-clamp conditions in vitro [98], which confirmed several postulates made by [10]. In addition, modeling results focus attention on the importance of low-threshold Ca2+-activated K+ channels in controlling dendritic excitability. Finally, the model was used to explore the likely accuracy of whole-cell voltage clamping experiments in this neuron.

Although several Purkinje cell models have previously been described in the literature, most have not included voltage-dependent conductances in the dendrites [716?18]. Models that did include ionic conductances in the dendrites either did not include all channels now known to exist [12] or were applied to a very limited set of questions [1]. In addition to exploring the mechanisms underlying this cells response to current injection, the current model also lays the groundwork for modeling and experimental studies of Purkinje cell responses to synaptic input [2].


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[16]   M Rapp, Y Yarom, and I Segev. The impact of parallel fiber background activity on the cable properties of cerebellar Purkinje cells. Neural Computation, 4:518–533, 1992.

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[19]   M Sugimori and RR Llinįs. Real-time imaging of calcium influx in mammalian cerebellar Purkinje cells in vitro. Proceedings of the National Academy of Sciences, 87:5084–5088, 1990.

[20]   Y Wang, JC Strahlendorf, and HK Strahlendorf. A transient voltage-dependent outward potassium current in mammalian cerebellar purkinje cells. Brain Research, 567:153–158, 1991.