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A New Approach for Determining Phase Response Curves Reveals that Purkinje Cells Can Act as Perfect Integrators

Phoka, E; Cuntz, H; Roth, A; Hausser, M; (2010) A New Approach for Determining Phase Response Curves Reveals that Purkinje Cells Can Act as Perfect Integrators. PLOS COMPUT BIOL , 6 (4) , Article e1000768. 10.1371/journal.pcbi.1000768. Green open access

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Abstract

Cerebellar Purkinje cells display complex intrinsic dynamics. They fire spontaneously, exhibit bistability, and via mutual network interactions are involved in the generation of high frequency oscillations and travelling waves of activity. To probe the dynamical properties of Purkinje cells we measured their phase response curves (PRCs). PRCs quantify the change in spike phase caused by a stimulus as a function of its temporal position within the interspike interval, and are widely used to predict neuronal responses to more complex stimulus patterns. Significant variability in the interspike interval during spontaneous firing can lead to PRCs with a low signal-to-noise ratio, requiring averaging over thousands of trials. We show using electrophysiological experiments and simulations that the PRC calculated in the traditional way by sampling the interspike interval with brief current pulses is biased. We introduce a corrected approach for calculating PRCs which eliminates this bias. Using our new approach, we show that Purkinje cell PRCs change qualitatively depending on the firing frequency of the cell. At high firing rates, Purkinje cells exhibit single-peaked, or monophasic PRCs. Surprisingly, at low firing rates, Purkinje cell PRCs are largely independent of phase, resembling PRCs of ideal non-leaky integrate-and-fire neurons. These results indicate that Purkinje cells can act as perfect integrators at low firing rates, and that the integration mode of Purkinje cells depends on their firing rate.

Type: Article
Title: A New Approach for Determining Phase Response Curves Reveals that Purkinje Cells Can Act as Perfect Integrators
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pcbi.1000768
Publisher version: http://dx.doi.org/10.1371/journal.pcbi.1000768
Language: English
Additional information: © 2010 Phoka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by the BBSRC, EPSRC, the Humboldt Foundation, Gatsby Charitable Foundation and The Wellcome Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: RESURGENT SODIUM CURRENT, NEURAL OSCILLATORS, RESETTING CURVES, ARM MOVEMENTS, NEURONS, SYNCHRONIZATION, DYNAMICS, LOCKING, CORTEX, RAT
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/142362
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