Abstract
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., 2:2) 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.
Highlights
Activity in large neuronal networks is characterized by precisely timed responses imposed on a continuous background discharge
Since large portions of the granular layer circuit can switch between theta-frequency oscillations and asynchronous discharge in relation to the attentive state (Pellerin and Lamarre, 1997, in the monkey; Hartmann and Bower, 1998; Hartmann and Bower, 2001, in the rat), Golgi cells may be endowed with specific mechanisms allowing them to follow the network activity pattern (Maex and De Schutter, 1998; Maex and De Schutter, 2005; Vos et al, 1999b)
Pacemaking is phase-reset by spikes To explore the interaction of spikes with low-frequency pacemaking, action potentials were elicited with retrograde stimulation while recording the Golgi cell in loose cell attached (LCA)
Summary
Activity in large neuronal networks is characterized by precisely timed responses imposed on a continuous background discharge. Since large portions of the granular layer circuit can switch between theta-frequency oscillations and asynchronous discharge in relation to the attentive state (Pellerin and Lamarre, 1997, in the monkey; Hartmann and Bower, 1998; Hartmann and Bower, 2001, in the rat), Golgi cells may be endowed with specific mechanisms allowing them to follow (and potentially influence) the network activity pattern (Maex and De Schutter, 1998; Maex and De Schutter, 2005; Vos et al, 1999b)
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