Abstract
Here we demonstrate that cerebellar stellate cells diffusionally isolate synaptically evoked signals in dendrites and are capable of input-specific synaptic plasticity. Sustained activity of parallel fibers induces a form of long-term depression that requires opening of calcium (Ca2+)-permeable AMPA-type glutamate receptors (CP-AMPARs) and signaling through class 1 metabotropic glutamate receptors (mGluR1) and CB1 receptors. This depression is induced by postsynaptic increases in Ca2+ concentration ([Ca2+]) and is limited to activated synapses. To understand how synapse-specific plasticity is induced by diffusible second messengers in aspiny dendrites, we examined diffusion of Ca2+ and small molecules within stellate cell dendrites. Activation of a single parallel fiber opened CP-AMPARs, generating long-lived Ca2+ transients that were confined to submicron dendritic stretches. The diffusion of Ca2+ was severely retarded due to interactions with parvalbumin and a general restriction of small molecule mobility. Thus stellate cell dendrites spatially restrict signaling cascades that lead from CP-AMPAR activation to endocannabinoid production and trigger the selective regulation of active synapses.
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Acknowledgements
We thank members of the Sabatini lab and W. Regehr for helpful discussions, and J. Corrie and D. Ogden for the gift of NPE-HPTS. This work was funded by the National Institutes of Neurological Disorders and Stroke (1 F31 NS049655-01) and Quan predoctoral fellowships to G.J.S.L., and a Burroughs Wellcome Fund Career Award, a Searle Scholar award, and McKnight Foundation Technological Innovations Awards to B.L.S.
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Supplementary information
Supplementary Fig. 1
Time course of an experiment showing the increase in failure rate after the induction of SCLTD. (PDF 191 kb)
Supplementary Fig. 2
Cyclopyazonic acid (CPA) abolishes caffeine-induced Ca2+ transients in cerebellar Purkinje cells. (PDF 3354 kb)
Supplementary Fig. 3
Summary of EPSC amplitudes in the tetanized and control pathways in the presence of the class 1 mGluR antagonist CPCCOEt (50 μM) (n = 7). (PDF 200 kb)
Supplementary Fig. 4
ΔG/Rsyn plotted against EPSC amplitude for 528 trials from the cells used in Figure 4 (n = 13 cells). (PDF 329 kb)
Supplementary Fig. 5
Analytical model of Ca2+ diffusion and clearance in SC dendrites. (PDF 616 kb)
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Soler-Llavina, G., Sabatini, B. Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells. Nat Neurosci 9, 798–806 (2006). https://doi.org/10.1038/nn1698
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DOI: https://doi.org/10.1038/nn1698
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