Abstract
Cerebellar granule cells (GrCs) convey information from mossy fibers (MFs) to Purkinje cells (PCs) via their parallel fibers (PFs). MF to GrC signaling allows transmission of frequencies up to 1 kHz and GrCs themselves can also fire bursts of action potentials with instantaneous frequencies up to 1 kHz. So far, in the scientific literature no evidence has been shown that these high-frequency bursts also exist in awake, behaving animals. More so, it remains to be shown whether such high-frequency bursts can transmit temporally coded information from MFs to PCs and/or whether these patterns of activity contribute to the spatiotemporal filtering properties of the GrC layer. Here, we show that, upon sensory stimulation in both un-anesthetized rabbits and mice, GrCs can show bursts that consist of tens of spikes at instantaneous frequencies over 800 Hz. In vitro recordings from individual GrC-PC pairs following high-frequency stimulation revealed an overall low initial release probability of ~0.17. Nevertheless, high-frequency burst activity induced a short-lived facilitation to ensure signaling within the first few spikes, which was rapidly followed by a reduction in transmitter release. The facilitation rate among individual GrC-PC pairs was heterogeneously distributed and could be classified as either “reluctant” or “responsive” according to their release characteristics. Despite the variety of efficacy at individual connections, grouped activity in GrCs resulted in a linear relationship between PC response and PF burst duration at frequencies up to 300 Hz allowing rate coding to persist at the network level. Together, these findings support the hypothesis that the cerebellar granular layer acts as a spatiotemporal filter between MF input and PC output (D’Angelo and De Zeeuw, 2009).
Highlights
Understanding synaptic efficacy is a critical step toward unraveling the computational properties of a neuronal network
We investigated the occurrence of bursting activity of granule cells (GrCs) by performing extracellular recordings in awake, behaving animals; we studied the impact of bursting activity in groups of parallel fibers (PFs) on excitatory postsynaptic currents (EPSCs) in Purkinje cells (PCs) using whole cell recordings in vitro; and we examined the impact of a burst within a single PF on a PC using paired GrC – PC recordings
Whereas at 200 Hz the steady-state had not reached its maximum yet, we saw a reduction of the plateau toward the end of the stimulus, pointing toward a presynaptic origin of this insufficiency. While these results show that release is optimized around 300 Hz, it is important to note that frequency-dependent limitation of release and presynaptic insufficiency probably occur at frequencies lower than reported here, because the results above apply to PF-activity as a bundle; in this experimental configuration inactivity of a particular fiber can be compensated for by activity from others, and unless all fibers are continuously active, equilibrium can be established at a higher level than would be possible for fibers independently
Summary
Understanding synaptic efficacy is a critical step toward unraveling the computational properties of a neuronal network. At rest they are rather silent, but following sensory activation GrCs display bursts of tens of action potentials with instantaneous frequencies up to 1 kHz (Isope and Barbour, 2002; Chadderton et al, 2004) As such GrCs may serve as a high-pass spatiotemporal filter, in which frequency dependent activity from MFs creates a time-window in which information can be relayed from MFs to PCs (D’Angelo and De Zeeuw, 2009; Mapelli et al, 2010; Solinas et al, 2010). When addressing the synaptic efficacy at the PF to PC input, the release probability (RP)
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