TY - JOUR
T1 - Fast-reset of pacemaking and theta-frequency resonance patterns in cerebellar Golgi cells
T2 - Simulations of their impact in vivo
AU - Solinas, Sergio
AU - Forti, Lia
AU - Cesana, Elisabetta
AU - Mapelli, Jonathan
AU - De Schutter, Erik
AU - D'Angelo, Egidio
PY - 2007/12/30
Y1 - 2007/12/30
N2 - 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., 2007 Front. Cell. 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.
AB - 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., 2007 Front. Cell. 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.
KW - Cerebellum
KW - Golgi cell
KW - Granular layer
KW - Modeling
KW - Phase-reset
KW - Resonance
UR - http://www.scopus.com/inward/record.url?scp=84890883328&partnerID=8YFLogxK
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U2 - 10.3389/neuro.03.004.2007
DO - 10.3389/neuro.03.004.2007
M3 - Article
AN - SCOPUS:84890883328
VL - 1
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
IS - DEC
M1 - 4
ER -