Present address: IBM T.J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Model of very fast (> 75 Hz) network oscillations generated by electrical coupling between the proximal axons of cerebellar Purkinje cells
Article first published online: 14 OCT 2008
© The Authors (2008). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 28, Issue 8, pages 1603–1616, October 2008
How to Cite
Traub, R. D., Middleton, S. J., Knöpfel, T. and Whittington, M. A. (2008), Model of very fast (> 75 Hz) network oscillations generated by electrical coupling between the proximal axons of cerebellar Purkinje cells. European Journal of Neuroscience, 28: 1603–1616. doi: 10.1111/j.1460-9568.2008.06477.x
- Issue published online: 14 OCT 2008
- Article first published online: 14 OCT 2008
- Received 10 June 2008, revised 23 August 2008, accepted 28 August 2008
- cerebellar cortex;
- gap junction;
- network model
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 (∼40 Hz, evoked by nicotine) or in isolation [evoked by nicotine in combination with γ-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 gNa inactivation, and experiments prolonging this inactivation time constant, with β-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.