Original Research Article
Fast-reset of pacemaking and theta-frequency resonance patterns in cerebellar golgi cells: Simulations of their impact in vivo
Sergio Solinas 1, 2, Lia Forti 1, Elisabetta Cesana 1, Jonathan Mapelli 1, Erik De Schutter 2, 3 and Egidio D`Angelo 1*
1 Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM, Italy
2 Theoretical Neurobiology, University of Antwerp, Belgium
3 Okinawa Institute of Science and Technology, Japan
2 Theoretical Neurobiology, University of Antwerp, Belgium
3 Okinawa Institute of Science and Technology, Japan
The Golgi cells are inhibitory interneurons of the cerebellar granular layer, which respond to afferent stimulation in vivo with a burst-pause sequence interrupting their irregular background low-frequency firing (Vos et al., 1999a. Eur. J. Neurosci. 11, 2621–2634). However, Golgi cells in vitro are regular pacemakers (Forti et al., 2006. J. Physiol. 574, 711–729), raising the question how their ionic mechanisms could impact on responses during physiological activity. Using patch-clamp recordings in cerebellar slices we show that the pacemaker cycle can be suddenly reset by spikes, making the cell highly sensitive to input variations. Moreover, the neuron resonates around the pacemaker frequency, making it specifically sensitive to patterned stimulation in the theta-frequency band. Computational analysis based on a model developed to reproduce Golgi cell pacemaking (Solinas et al., 2008 Front. Neurosci., 1:2) predicted that phase-reset required spike-triggered activation of SK channels and that resonance was sustained by a slow voltage-dependent potassium current and amplified by a persistent sodium current. Adding balanced synaptic noise to mimic the irregular discharge observed in vivo, we found that pacemaking converts into spontaneous irregular discharge, that phase-reset plays an important role in generating the burst-pause pattern evoked by sensory stimulation, and that repetitive stimulation at theta-frequency enhances the time-precision of spike coding in the burst. These results suggest that Golgi cell intrinsic properties exert a profound impact on time-dependent signal processing in the cerebellar granular layer.
Keywords: golgi cell, resonance, phase-reset, cerebellum, granular layer, modeling
Copyright: © 2007 Solinas, Forti, Cesana, Mapelli, De Schutter and D`Angelo. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Egidio D’Angelo, Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM, Via Forlanini 6, I-27100 Pavia, Italy. e-mail: dangelo@unipv.it
Citation: Solinas S, Forti L, Cesana E, Mapelli J, De Schutter E and D`Angelo E (2007) Fast-reset of pacemaking and theta-frequency resonance patterns in cerebellar golgi cells: Simulations of their impact in vivo. Front. Cell. Neurosci. (2007) 1:4. doi:10.3389/neuro.03.004.2007
Received: 26 November 2007; paper pending published: 01 December 2007; accepted: 07 December 2007; published online: 30 December 2007.
Edited by:
Alexander Borst, Max Planck Institute of Neurobiology, Germany
Reviewed by:
Yosef Yarom, Hebrew University, Israel
Hermann Cuntz, University College London, UK
Hermann Cuntz, University College London, UK
*Correspondence: Egidio D’Angelo, Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM, Via Forlanini 6, I-27100 Pavia, Italy. e-mail: dangelo@unipv.it


