PT - JOURNAL ARTICLE AU - Antoine M. Valera AU - Frédéric Doussau AU - Bernard Poulain AU - Boris Barbour AU - Philippe Isope TI - Adaptation of Granule Cell to Purkinje Cell Synapses to High-Frequency Transmission AID - 10.1523/JNEUROSCI.3175-11.2012 DP - 2012 Feb 29 TA - The Journal of Neuroscience PG - 3267--3280 VI - 32 IP - 9 4099 - http://www.jneurosci.org/content/32/9/3267.short 4100 - http://www.jneurosci.org/content/32/9/3267.full SO - J. Neurosci.2012 Feb 29; 32 AB - The mossy fiber (MF)–granule cell (GC) pathway conveys multiple modalities of information to the cerebellar cortex, converging on Purkinje cells (PC), the sole output of the cerebellar cortex. Recent in vivo experiments have shown that activity in GCs varies from tonic firing at a few hertz to phasic bursts >500 Hz. However, the responses of parallel fiber (PF)–PC synapses to this wide range of input frequencies are unknown, and there is controversy regarding several frequency-related parameters of transmission at this synapse. We performed recordings of unitary synapses and combined variance–mean analysis with a carefully adapted extracellular stimulation method in young and adult rats. We show that, although the probability of release at individual sites is low at physiological calcium concentration, PF–PC synapses release one or more vesicles with a probability of 0.44 at 1.5 mm [Ca2+]e. Paired-pulse facilitation was observed over a wide range of frequencies; it renders burst inputs particularly effective and reproducible. These properties are primarily independent of synaptic weight and age. Furthermore, we show that the PF–PC synapse is able to sustain transmission at very high frequencies for tens of stimuli, as a result of accelerated vesicle replenishment and an apparent recruitment of release site vesicles, which appears to be a central mechanism of paired-pulse facilitation at this synapse. These properties ensure that PF–PC synapses possess a dynamic range enabling the temporal code of MF inputs to be transmitted reliably to the PC.