The Golgi cell's role in the cerebellar microcircuitry: coincidence detection and STDP at mossy fiber - Golgi cell synapse

Today it's established that the cerebellum is an highly patterned structure organized into functional modules that enhance processing power during cerebellar-dependent behaviours, covering also different roles in non-motor functions such as cognition and emotion. Its ability to elaborate information in milliseconds suggests that timing adaption is a cerebellar circuitry’s fundamental event. To allow correct information processing, the cerebellum needs the presence of a precisely organized network. The extent to which changes in cerebellar transmission alter the output is thought to depend mainly on inhibitory interactions among cells. A key role in these interactions is played by Golgi cells, which modulate the inputs that must be relayed to Purkinje cells. On one side, as a result of the feedforward inhibition, on the other side through feedback inhibition. Golgi cells act as a temporal filter on the granule cells' activity when activated by mossy fibers in the granular layer, restricting their window time of spikes emission. In this way, the transmission of a limited amount of information can be projected to the neurons in the upper layers, by parallel fibers. Alternatively, by the way of tonic inhibition, Golgi cells downturn granule cells' excitability decreasing their resistance. These mechanisms are essential, and their function is separating information to be conveyed to Purkinje cells from the background noise. In the molecular layer, granule cells, activated by mossy fibers, excite via parallel fibers the Purkinje cells and Golgi cells apical dendrites. Golgi cells back-inhibit granule cells dendrites located around their axonal plexuses. Despite being activated by mossy fibers, granule cells decline their capability to activate, via parallel fibers, Purkinje cells, and molecular layer interneurons. Golgi cells are crucial for determining precise spatiotemporal patterns of activity in the cerebellar cortex. A long-term synaptic plasticity is an event that involves modifications in neuronal and synaptic activity, and the cerebellar network act by these long-term modifications to assure real-time processing in dynamic sensorimotor contexts. A recent study demonstrated the presence of Hebbian STDP at mossy fiber-granule cell synapses in the rat cerebellum. Specifically, STDP occurred maximally with a time window of ±25 ms between the pre and postsynaptic activity, following a mossy fiber stimulation of 6-10 Hz, related to the theta-frequency band at which coherent oscillations pulse in the granular layer. Since Golgi cells' role in modulating the gain and timing of signals conveyed to Purkinje cells, theoretical models predicted STDP at mossy fiber-Golgi cells synapse as a pivotal mechanism to support Golgi cells inhibitory role at the cerebellar input stage. Recently, computational models explored the mechanism by which Golgi cells dendrites integrate and process the input transmitted by parallel and mossy fibers. More precisely, these models suggested that, after stimulation of parallel fibers, inputs are conveyed into Golgi cells apical dendrites which promote spikes generation in the axonal initial segment. These, backpropagate into basal dendrites where mossy fiber inputs were previously transferred. STDP long-term potentiation promotion at Golgi cell-mossy fiber synapse. Vice versa, when parallel fiber input precedes mossy fiber input, STDP long-term depression would be induced. Therefore, dendritic processing and plasticity in Golgi cells may depend on the time window between the inputs received. This suggests that the Golgi cell may act as a signals coincidence detector between parallel and mossy fibers. Electrophysiological approaches validate all these predictions, starting elucidating the role of Golgi cells dendritic processing in integrating information received and that of spike timing in modulating plasticity at the cerebellar granular layer.