Fast-reset of pacemaking and theta-frequency resonance patterns in cerebellar golgi cells: Simulations of their impact in vivo

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 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.

Current source density correlates of cerebellar Golgi and Purkinje cell responses to tactile input

“…Although the silent period has long been observed in other GoC preparations (Eccles et al 1966), its function and origin have remained unclear. Proposed mechanisms are intrinsic membrane currents of the GoC (Solinas et al 2007), activation of metabotropic glutamate receptors of type 2 (Watanabe et al 1998), or the dynamics of the network (Dugué et al 2009;Maex and De Schutter 1998). The clear current source we found in the granular layer near the GoC recording position and coincident with the silent period (Figs.…”

“…However, a modeling study could not exclude the slowly propagating parallel fibers as a secondary source of excitation (Volny-Luraghi et al 2002), and alternative pathways exist (see DISCUSSION). In addition, both the initial burst-like response and the long-lasting suppression could reflect the activation of afferent synapses or, alternatively, be generated by intrinsic membrane mechanisms (Solinas et al 2007). Moreover, despite their stereotypical response patterns to peripheral stimulation, GoCs have larger receptive fields and a lower response selectivity than mossy fibers (Prsa et al 2009).…”

Reviewing Multi-Disciplinary Papers: a Challenge in Neuroscience?

“…In many cases modeling has led to surprising results contradicting, in part, the experimental expectations. For example, modeling showed that a spatial separation of calcium channel types was not needed to generate both calcium plateaus and calcium spikes in Purkinje cells (De Schutter and Bower 1994) and that in cerebellar Golgi cells the I h current does not actively participate to subthreshold oscillations that drive spontaneous firing (Solinas et al 2007). At a more general level, combined modeling and experimental work has shown that homeostatic control of channels make specific links between channels and firing behaviors tenuous and that, in many cases trying to explain data with a unique model may be a fallacy (Achard and De Schutter 2006;Marder and Goaillard 2006).…”

Resonance properties of different neuronal populations in the immature mouse neocortex

“…The persistent Na + current (I NaP ) is a threshold current which have been found in neocortical and hippocampal pyramidal neurons (French and Gage, 1985;Stafstrom et al, 1985), hippocampal and cerebellar interneurons (Solinas et al, 2007;Boehlen et al, 2011), and many other neurons in different brain regions (Crill, 1996). I NaP was activated positive to -65 mV and could be blocked by tetrodoxin (TTX, 1 µM).…”

“…Persistent Na + currents have been shown to contribute importantly to intrinsic oscillations of some central neurons (Klink and Alonso, 1993;Gutfreund et al, 1995;Hutcheon et al, 1996;Pape and Driesang, 1998;Hu et al, 2002), in cerebellar interneurons (Solinas et al, 2007) and hippocampal stratum radiatum interneurons (Boehlen et al, 2011). In rat neocortex, regular spiking (RS) and intrinsic bursting (IB) neurons exhibited resonance at resting membrane potentials.…”