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Model of very fast (> 75 Hz) network oscillations generated by electrical coupling between the proximal axons of cerebellar Purkinje cells

Lookup NU author(s): Dr Steven Middleton, Professor Thomas Knopfel, Professor Miles Whittington


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Very fast oscillations (VFO; > 75 Hz) occur transiently in vivo, in the cerebellum of mice genetically modified to model Angelman syndrome, and in a mouse model of fetal alcohol syndrome. We recently reported VFO in slices of mouse cerebellar cortex (Crus I and II of ansiform and paramedian lobules), either in association with gamma oscillations (similar to 40 Hz, evoked by nicotine) or in isolation [evoked by nicotine in combination with gamma-aminobutyric acid (GABA)(A) receptor blockade]. The experimental data suggest a role for electrical coupling between Purkinje cells (blockade of VFO by drugs reducing gap junction conductance and spikelets in some Purkinje cells); and the data suggest the specific involvement of Purkinje cell axons (because of field oscillation maxima in the granular layer). We show here that a detailed network model (1000 multicompartment Purkinje cells) replicates the experimental data when gap junctions are located on the proximal axons of Purkinje cells, provided sufficient spontaneous firing is present. Unlike other VFO models, most somatic spikelets do not correspond to axonal spikes in the parent axon, but reflect spikes in electrically coupled axons. The model predicts gating of VFO frequency by g(Na) inactivation, and experiments prolonging this inactivation time constant, with beta-pompilidotoxin, are consistent with this prediction. The model also predicts that cerebellar VFO can be explained as an electrically coupled system of axons that are not intrinsic oscillators: the electrically uncoupled cells do not individually oscillate (in the model) and axonal firing rates are much lower in the uncoupled state than in the coupled state.

Publication metadata

Author(s): Traub RD, Middleton SJ, Knopfel T, Whittington MA

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2008

Volume: 28

Issue: 8

Pages: 1603-1616

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd.


DOI: 10.1111/j.1460-9568.2008.06477.x


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