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Synapse-specific plasticity and compartmentalized signaling in cerebellar stellate cells

Nature Neuroscience volume 9, pages 798–806 (2006)Cite this article

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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Figure 1: Trains of stimuli induce input-specific LTD at the parallel fiber–to–stellate cell synapse.
Figure 2: SCLTD requires AMPAR-mediated postsynaptic Ca2+ increases and CB1 receptor activation.
Figure 3: Synaptically evoked Ca2+ transients in dendrites of cerebellar stellate cells.
Figure 4: Δ[Ca2+]syn is restricted to submicron dendritic regions.
Figure 5: CP-AMPARs mediate Δ[Ca2+]syn.
Figure 6: Mechanisms of Ca2+ compartmentalization in stellate cell dendrites.
Figure 7: Δ[Ca]syn remains compartmentalized during sustained synaptic activity.
Figure 8: The input specificity of LTD is maintained over short distances.

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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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  1. Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Gilberto J Soler-Llavina & Bernardo L Sabatini

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  1. Gilberto J Soler-Llavina
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Correspondence to Bernardo L Sabatini.

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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)

Supplementary Methods (PDF 309 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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