Abstract
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. 2:4).
Highlights
Oscillations are one of the most prominent features of brain activity (Buzsaki, 2006)
The Golgi cell was recently proposed to express a characteristic set of ionic currents
Each one of these is endowed with unique gating and kinetics properties: INa-p activates rapidly with depolarization in the subthreshold region, Ih slowly deactivates with depolarization, IK-AHP activates briskly upon Ca2þ entry and remains activated for tens of milliseconds, and IK-slow activates slowly and progressively in the subthreshold region during sustained depolarization
Summary
Oscillations are one of the most prominent features of brain activity (Buzsaki, 2006). Numerous neurons in the brain show pacemaker activity exploiting a variety of ionic mechanisms (Hutcheon and Yarom, 2000; Koch, 1999; Llinas, 1988; Yamada et al, 1998). The h-current determines the depolarizing ramp leading to LVA channel activation and to the calcium spike, which triggers a spike bursts before inactivating and concluding the cycle. These pacemakers cannot be perturbed and drive fast sodium spike bursts. Probably more diffused pacemaker neurons, show smaller oscillations in the subthres-
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