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Purkinje cells in awake behaving animals operate at the upstate membrane potential

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Figure 1: Simple spike pauses and signs of toggling are dramatically increased by anesthetics.
Figure 2: Motor performance or motor learning does not significantly affect bistability in Purkinje cells.


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Research was supported by Neuro-Bsik (C.I.D.Z.), ZonMw (C.I.D.Z. and M.S.), NWO (C.I.D.Z., M.A.F. and M.T.G.D.J.), EEC (C.I.D.Z.), EUR (M.T.S. and M.T.G.D.J.) and NWO-VIDI (M.A.F. and B.H.J.W.).

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Supplementary Fig. 1

Membrane potential bistability of Purkinje cells in vivo under anesthesia. (a) Top panel left: whole-cell recording of a Purkinje cell in an isoflurane anesthetized mouse showing two states of membrane potential; a hyperpolarized downstate and a depolarized upstate (asterisks indicate complex spikes). Right: enlargement of a transition from down- to upstate related to a complex spike. Bottom panel left: example of a Purkinje cell in an isoflurane anesthetized mouse displaying three states: a downstate, an upstate and an even more depolarized overstate. Right: enlargement showing that both transitions to a higher state are related to the occurrence of a complex spike. (b) Purkinje cell recording from a ketamine/xylazine anesthetized mouse operating partly in the upstate (left) and showing a weaker temporal relation between the occurrence of complex spikes and transitions (right). Note that throughout all examples the upstate displays continuous firing whereas the downstate and overstate are silent except for the complex spikes. (PDF 763 kb)

Supplementary Fig. 2

Extracellularly recorded complex spike and simple spike activities perfectly correspond to intracellularly recorded action potentials. (a) Simultaneous intracellular and extracellular recordings of the same Purkinje cell show a perfect match between action potentials (top) and simple spikes (bottom). (b) Enlargement of a complex spike, displaying the typical slow (calcium) wave in the intracellular recording and the complex spike waveform and climbing fiber pause in the extracellular recording. (c) Histogram of the time difference between intracellular action potentials and extracellular simple spikes. (d) Analysis of approximately 6 seconds of dual recording with each simple spike represented by a vertical bar (this picture only represents a short period of the recordings which lasted several minutes and which entirely showed a perfect match). Together with (c) these figures demonstrate a 100% match at a time resolution of 1.0 ms. (e) Intracellular negative current injection is not seen in the extracellular recording excluding the possibility that the dual recordings result in cross-talk between the two electrodes. (PDF 1245 kb)

Supplementary Fig. 3

Purkinje cell recorded in a mouse before and after cessation of anesthesia (corresponding to traces shown in Figure 1g). (a) Raw trace of the entire recording showing that pauses in simple spike firing frequency and signs of toggling that can be seen during anesthesia are no longer present after cessation of the application of isoflurane (b) Top panel: raw traces aligned in time by complex spike onset. Bottom panel: averaged signal showing the complex spike waveform. (c) Peri complex spike time histogram following waveform analysis and threshold discrimination (according to dashed line in a); note the apparent climbing fiber pause. (PDF 885 kb)

Supplementary Fig. 4

Silent states in Purkinje cells, suggestive for bistability, can be evoked by anesthetics, but not by subjecting the animal to motor performance (OKR) or motor learning (VVT) tasks. (a) Skewness and kurtosis, two characteristics of the shape of ISSI distributions, are both increased by anesthetics. Dashed lines indicate skewness and kurtosis values of a lognormal distribution. (b) The percentage of cells with a unimodal ISSI distribution was reduced by both anesthetics, but not by the optokinetic reflex (OKR) or visuovestibular training (VVT). (c) Using a minimum pause length of 500 ms (approximately 3 times the maximum ISSI found in the upstate), both the percentage of pausing time and pausing cells are higher under anesthesia. (d) The percentage of times a complex spike putatively triggered a change in simple spike firing (i.e. sign of toggling) is also higher under both forms of anesthetics. (PDF 657 kb)

Supplementary Methods (PDF 117 kb)

Supplementary Data (PDF 111 kb)

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Schonewille, M., Khosrovani, S., Winkelman, B. et al. Purkinje cells in awake behaving animals operate at the upstate membrane potential. Nat Neurosci 9, 459–461 (2006).

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