Glutamate release during LTD at cerebellar climbing fiber–Purkinje cell synapses

Abstract

It is widely thought that persistent, use-dependent alterations in synaptic strength such as long-term synaptic potentiation (LTP) and depression (LTD) underlie at least a portion of memory traces in the brain1,2, but the exact cellular locus of expression for these alterations remains to be determined. They could be expressed presynaptically as a decrease in transmitter release, postsynaptically as a decrease in the synaptic current evoked by a fixed delivery of transmitter, as an increase in the number of functional synaptic contacts, or by a combination of these mechanisms. Here we report that LTD at the climbing fiber–Purkinje cell synapse in rat cerebellum was not associated with changes in a synaptic cleft glutamate transient, indicating that this type of LTD is most likely expressed postsynaptically.

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Figure 1: The degree of blockade by the rapidly-dissociating AMPA receptor antagonist γ-DGG increased during paired-pulse depression (PPD, which involves a reduction of transmitter release) but not during long-term depression (LTD) of climbing-fiber EPSCs.
Figure 2: Postsynaptic reduction of synaptic transmission designed to mimic climbing-fiber LTD did not alter blockade by γ-DGG.

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Acknowledgements

The authors wish to thank D. Gurfel and R. Bock for technical assistance and D. Bergles, W. Zhang, J.H. Shin, A. Sdrulla and S. Morris for useful suggestions. This work was supported by MH51106 and MH01590 and the Develbiss Fund.

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Correspondence to David J. Linden.

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The authors declare no competing financial interests.

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Shen, Y., Hansel, C. & Linden, D. Glutamate release during LTD at cerebellar climbing fiber–Purkinje cell synapses. Nat Neurosci 5, 725–726 (2002). https://doi.org/10.1038/nn895

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