Abstract
The Golgi cells are the main inhibitory interneurons of the cerebellar granular layer. Although recent works have highlighted the complexity of their dendritic organization and synaptic inputs, the mechanisms through which these neurons integrate complex input patterns remained unknown. Here we have used 8 detailed morphological reconstructions to develop multicompartmental models of Golgi cells, in which Na, Ca, and K channels were distributed along dendrites, soma, axonal initial segment and axon. The models faithfully reproduced a rich pattern of electrophysiological and pharmacological properties and predicted the operating mechanisms of these neurons. Basal dendrites turned out to be more tightly electrically coupled to the axon initial segment than apical dendrites. During synaptic transmission, parallel fibers caused slow Ca-dependent depolarizations in apical dendrites that boosted the axon initial segment encoder and Na-spike backpropagation into basal dendrites, while inhibitory synapses effectively shunted backpropagating currents. This oriented dendritic processing set up a coincidence detector controlling voltage-dependent NMDA receptor unblock in basal dendrites, which, by regulating local calcium influx, may provide the basis for spike-timing dependent plasticity anticipated by theory.
Highlights
The cerebellar Golgi cell [1,2,3] is the principal inhibitory interneuron of the cerebellar granular layer [4] and is supposed to play a critical role for spatio-temporal reconfiguration of incoming inputs by regulating neurotransmission and synaptic plasticity along the mossy fiber–granule cell pathway [5,6,7]
Fundamental issues that remain unexplored are how synaptic inputs control Golgi cell spike generation and whether dendritic processing provides the basis for spike-timing dependent plasticity (STDP), which has been predicted by theory [13]
The present simulations, beyond faithfully reproducing the rich pattern of Golgi cell electrophysiological properties recorded in vitro and in vivo, suggest that Golgi cells operate as oriented coincidence detectors of parallel fiber and mossy fiber activity
Summary
The cerebellar Golgi cell [1,2,3] is the principal inhibitory interneuron of the cerebellar granular layer [4] and is supposed to play a critical role for spatio-temporal reconfiguration of incoming inputs by regulating neurotransmission and synaptic plasticity along the mossy fiber–granule cell pathway [5,6,7]. The excitatory inputs are conveyed by mossy fibers and granule cell ascending axons on the basal dendrites and by parallel fibers on the apical dendrites [9]. The Golgi cells eventually inhibit large fields of granule cells through an extended axonal plexus. Fundamental issues that remain unexplored are how synaptic inputs control Golgi cell spike generation and whether dendritic processing provides the basis for spike-timing dependent plasticity (STDP), which has been predicted by theory [13]. Mossy fiber–Golgi cell synapses express NMDA channels (fundamental for synaptic plasticity) at mossy fiber synapses [9] and the dendrites express a diversified set of Ca, Na and K ionic channels [14] that could impact on dendritic computation. A prediction about the possible interactions of these multiple active properties is quite hard and requires a detailed computational analysis of the electrogenic architecture of the neuron and of synaptic integration
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