A stable proportion of Purkinje cell inputs from parallel fibers are silent during cerebellar maturation – pnas.org

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Edited by Huda Y. Zoghbi, Baylor College of Medicine, Houston, TX, and approved September 30, 2021 (received for review December 3, 2020)
Synapses connecting granule cells to Purkinje neurons are considered essential sites for learning in the cerebellum. Strikingly, most of them appear to be silent: they do not transmit any electrical information. This may relate to information storage capacity and reliability, which are expected to improve during postnatal maturation. Here, we quantify the proportion of silent synapses in mice by combining optogenetic mapping of synaptic inputs and Purkinje neuron patch-clamp recording. We show that this proportion remains stable between the stage immediately following the postnatal establishment of cerebellar circuitry and 3 wk later when cerebellar function has maturated, presumably as a result of natural learning processes. Our results suggest that information storage capacity and reliability are optimized early during cerebellar maturation.
Cerebellar Purkinje neurons integrate information transmitted at excitatory synapses formed by granule cells. Although these synapses are considered essential sites for learning, most of them appear not to transmit any detectable electrical information and have been defined as silent. It has been proposed that silent synapses are required to maximize information storage capacity and ensure its reliability, and hence to optimize cerebellar operation. Such optimization is expected to occur once the cerebellar circuitry is in place, during its maturation and the natural and steady improvement of animal agility. We therefore investigated whether the proportion of silent synapses varies over this period, from the third to the sixth postnatal week in mice. Selective expression of a calcium indicator in granule cells enabled quantitative mapping of presynaptic activity, while postsynaptic responses were recorded by patch clamp in acute slices. Through this approach and the assessment of two anatomical features (the distance that separates adjacent planar Purkinje dendritic trees and the synapse density), we determined the average excitatory postsynaptic potential per synapse. Its value was four to eight times smaller than responses from paired recorded detectable connections, consistent with over 70% of synapses being silent. These figures remained remarkably stable across maturation stages. According to the proposed role for silent synapses, our results suggest that information storage capacity and reliability are optimized early during cerebellar maturation. Alternatively, silent synapses may have roles other than adjusting the information storage capacity and reliability.
Author contributions: J.-P.K. and P.M. designed research; S.H., R.L., M. Lerat, M. Le, K.L., J.L., J.-P.K., and P.M. performed research; S.H., R.L., J.L., J.-P.K., and P.M. analyzed data; V.C. provided laboratory facilities; and V.C., J.L., J.-P.K., and P.M. wrote the paper.
The authors declare no competing interest.
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