Computational reconstruction of pacemaking and intrinsic electroresponsiveness in cerebellar golgi cells

Frontiers in Cellular Neuroscience

Egidio D‘Angelo²  Lia Forti²  Elisabetta Cesana²  Jonathan Mapelli²  Erik De Schutter³  Sergio Solinas³ 

[1] Computational Neuroscience Unit, Okinawa Institute of Science and Technology;Department of Cellular and Molecular Physiological and Pharmacological Sciences, University of Pavia and CNISM;Theoretical Neurobiology, University of Antwerp;

关键词: Cerebellum;    modeling;    golgi cell;    granular layer;    pacemaking;   

DOI  :  10.3389/neuro.03.002.2007

来源: DOAJ

【 摘 要 】

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 (I_Na-p), an h current (I_h), an SK-type calcium-dependent potassium current (I_K-AHP), and a slow M-like potassium current (I_K-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. I_Na-p and I_K-slow emerged as the critical determinants of oscillations. I_h also played a role by setting the oscillatory mechanism into the appropriate membrane potential range. I_K-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 (I_Na-r) and an A-current (I_K-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).

【 授权许可】

Unknown