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Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover

Abstract

Spillover of glutamate under physiological conditions has only been established as an adjunct to conventional synaptic transmission. Here we describe a pure spillover connection between the climbing fiber and molecular layer interneurons in the rat cerebellar cortex. We show that, instead of acting via conventional synapses, multiple climbing fibers activate AMPA- and NMDA-type glutamate receptors on interneurons exclusively via spillover. Spillover from the climbing fiber represents a form of glutamatergic volume transmission that could be triggered in a regionalized manner by experimentally observed synchronous climbing fiber activity. Climbing fibers are known to direct parallel fiber synaptic plasticity in interneurons, so one function of this spillover is likely to involve controlling synaptic plasticity.

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Figure 1: Putative climbing fiber responses show paired-pulse depression.
Figure 2: Purkinje cell and interneuron responses to common climbing fiber.
Figure 3: Climbing fiber inputs activate AMPA- and NMDA-type glutamate receptors.
Figure 4: The climbing fiber conductance is long lasting.
Figure 5: Interneurons are innervated by multiple climbing fibers.
Figure 6: mEPSCs of the climbing fiber could not be detected.
Figure 7: Blocking glutamate uptake potentiates the climbing fiber input.
Figure 8: The climbing fiber input is highly sensitive to block by low-affinity AMPA receptor antagonists.

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Acknowledgements

We thank H. Jörntell for help in identifying the climbing fiber input to interneurons; D. Colquhoun and A. Hawkes for showing us the test for comparing two Poisson rates; C. Mulle for the gift of GYKI 53655 and advice; D. Attwell, T. Otis and D. DiGregorio for comments on the manuscript; and C. Léna, A. Feltz, Y. Otsu and many other members of the Laboratoire de Neurobiologie for helpful discussion and comments on the manuscript. We gratefully acknowledge the support of the Agence Nationale de la Recherche, Fondation Fyssen (fellowship to G.S.), Centre National de la Recherche Scientifique and Ecole Normale Supérieure.

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Correspondence to Boris Barbour.

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Szapiro, G., Barbour, B. Multiple climbing fibers signal to molecular layer interneurons exclusively via glutamate spillover. Nat Neurosci 10, 735–742 (2007). https://doi.org/10.1038/nn1907

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