Abstract
In vitro, cerebellar Purkinje cells can intrinsically fire action potentials in a repeating trimodal or bimodal pattern. The trimodal pattern consists of tonic spiking, bursting, and quiescence. The bimodal pattern consists of tonic spiking and quiescence. It is unclear how these firing patterns are generated and what determines which firing pattern is selected. We have constructed a realistic biophysical Purkinje cell model that can replicate these patterns. In this model, Na+/K+ pump activity sets the Purkinje cell's operating mode. From rat cerebellar slices we present Purkinje whole cell recordings in the presence of ouabain, which irreversibly blocks the Na+/K+ pump. The model can replicate these recordings. We propose that Na+/K+ pump activity controls the intrinsic firing mode of cerbellar Purkinje cells.
Highlights
The cerebellum coordinates the execution and adaptation of motor behaviours [1]
The Purkinje cell model can replicate the trimodal pattern of spontaneous firing In the absence of synaptic input, the model Purkinje cell fires spontaneously in a repeating trimodal pattern that consists of tonic spiking (t), bursting (b) and silence (s) (Fig. 1C)
We suggest that at the foundation of the Purkinje cell’s intrinsic multimodality, there is the working of just a single molecular species – the Na+/ K+ pump - and we propose that it sets the Purkinje cell as persistently quiescent or spontaneously firing in trimodal or bimodal patterns
Summary
The cerebellum coordinates the execution and adaptation of motor behaviours [1]. Cerebellar architecture is based on repeats of a well defined connectivity motif, at the centre of which is the Purkinje cell. The repeat length of the trimodal pattern is reportedly fixed for a single Purkinje cell but has been observed to vary among different Purkinje cells, in a range from 20 seconds to 20 minutes [3] This second to minute duration of the trimodal behaviour is distinct from the millisecond timeframe of ion channel kinetics. Changes in intra-and-extra-cellular ion concentrations can span seconds to minutes [7] and could drive the transition of modes in the trimodal pattern We test this hypothesis with a realistic biophysical Purkinje cell model that can replicate the trimodal firing pattern. In this model, the Na+/K+ pump controls the transition from tonic to burst firing by regulating the extracellular K+ concentration ([K+]o), which rules a Kv1.2 K+ channel ‘‘gate’’ to bursting. The Na+/K+ pump’s electrogenicity generates the quiescent mode, upon regulation by the intracellular Na+
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