Original Research Article
Computational reconstruction of pacemaking and intrinsic electroresponsiveness in cerebellar golgi cells
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 Computational Neuroscience Unit , Okinawa Institute of Science and Technology, Japan
2 Theoretical Neurobiology, University of Antwerp, Belgium
3 Computational Neuroscience Unit , Okinawa Institute of Science and Technology, Japan
The Golgi cells have been recently shown to beat regularly in vitro (Forti et al., 2006. J. Physiol. 574, 711–729). Four main currents were shown to be involved, namely a persistent sodium current (INa-p), an h current (Ih), an SK-type calcium-dependent potassium current (IK-AHP), and a slow M-like potassium current (IK-slow). These ionic currents could take part, together with others, also to different aspects of neuronal excitability like responses to depolarizing and hyperpolarizing current injection. However, the ionic mechanisms and their interactions remained largely hypothetical. In this work, we have investigated the mechanisms of Golgi cell excitability by developing a computational model. The model predicts that pacemaking is sustained by subthreshold oscillations tightly coupled to spikes. INa-p and IK-slow emerged as the critical determinants of oscillations. Ih also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. IK-AHP, though taking part to the oscillation, appeared primarily involved in regulating the ISI following spikes. The combination with other currents, in particular a resurgent sodium current (INa-r) and an A-current (IK-A), allowed a precise regulation of response frequency and delay. These results provide a coherent reconstruction of the ionic mechanisms determining Golgi cell intrinsic electroresponsiveness and suggests important implications for cerebellar signal processing, which will be fully developed in a companion paper (Solinas et al., 2008. Front. Neurosci. 1:4).
Keywords: golgi cell, pacemaking, 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) Computational reconstruction of pacemaking and intrinsic electroresponsiveness in cerebellar golgi cells. Front. Cell. Neurosci. (2007) 1:2. doi:10.3389/neuro.03.002.2007
Received: 30 August 2007; paper pending published: 21 September 2007; accepted: 07 December 2007; published online: 30 December 2007.
Edited by:
Alexander Borst, Max Planck Institute of Neurobiology, Germany
Reviewed by:
Hermann Cuntz, University College London, UK
Yosef Yarom, Hebrew University, Israel
Yosef Yarom, Hebrew University, Israel
*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


