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Integration of quanta in cerebellar granule cells during sensory processing

Abstract

To understand the computations performed by the input layers of cortical structures, it is essential to determine the relationship between sensory-evoked synaptic input and the resulting pattern of output spikes. In the cerebellum, granule cells constitute the input layer, translating mossy fibre signals into parallel fibre input to Purkinje cells1. Until now, their small size and dense packing1,2 have precluded recordings from individual granule cells in vivo. Here we use whole-cell patch-clamp recordings to show the relationship between mossy fibre synaptic currents evoked by somatosensory stimulation and the resulting granule cell output patterns. Granule cells exhibited a low ongoing firing rate, due in part to dampening of excitability by a tonic inhibitory conductance mediated by GABAA (γ-aminobutyric acid type A) receptors. Sensory stimulation produced bursts of mossy fibre excitatory postsynaptic currents (EPSCs) that summate to trigger bursts of spikes. Notably, these spike bursts were evoked by only a few quantal EPSCs, and yet spontaneous mossy fibre inputs triggered spikes only when inhibition was reduced. Our results reveal that the input layer of the cerebellum balances exquisite sensitivity with a high signal-to-noise ratio. Granule cell bursts are optimally suited to trigger glutamate receptor activation3,4,5 and plasticity6,7,8 at parallel fibre synapses, providing a link between input representation and memory storage in the cerebellum.

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Figure 1: Intrinsic membrane properties of granule cells in vivo.
Figure 2: Low spontaneous firing rates are enforced by tonic inhibition in vivo.
Figure 3: Evoked sensory responses in granule cells in vivo.
Figure 4: The relationship between mossy fibre input and granule cell output.

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Acknowledgements

We thank B. Clark, J. Davie, M. Farrant and A. Roth for comments. This work was supported by grants from the European Union (M.H.), Wellcome Trust (M.H. and T.W.M.), Gatsby Foundation (M.H.), NHMRC (T.W.M.) and by a UCL Graduate School Research Scholarship (P.C.). T.W.M. acknowledges the MPI für medizinische Forschung, Heidelberg, for support.

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Correspondence to Michael Häusser.

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Supplementary information

Supplementary Methods (DOC 29 kb)

Supplementary Figure 1

The relationship between bursting input and bursting output in cerebellar granule cells in vivo. (PDF 132 kb)

Supplementary Figure 2

Contribution of postsynaptic nonlinearities to granule cell integration in vivo. (PDF 151 kb)

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Chadderton, P., Margrie, T. & Häusser, M. Integration of quanta in cerebellar granule cells during sensory processing. Nature 428, 856–860 (2004). https://doi.org/10.1038/nature02442

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