Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability

Bernardinelli, Yann; Randall, Jerome; Janett, Elia; Nikonenko, Irina; König, Stéphane; Jones, Emma Victoria; Flores, Carmen E.; Murai, Keith K.; Bochet, Christian G.; Holtmaat, Anthony; Muller, Dominique

doi:10.1016/j.cub.2014.06.025

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Journal article

Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability

Bernardinelli, Yann Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
Randall, Jerome Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
Janett, Elia Department of Chemistry, University of Fribourg, Switzerland
Nikonenko, Irina Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
König, Stéphane Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
Jones, Emma Victoria Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Research Institute of the McGill University Health Centre, Montreal General Hospital, Canada
Flores, Carmen E. Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
Murai, Keith K. Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Research Institute of the McGill University Health Centre, Montreal General Hospital, Canada
Bochet, Christian G. Department of Chemistry, University of Fribourg, Switzerland
Holtmaat, Anthony Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland
Muller, Dominique Department of Basic Neurosciences, Medical School, University of Geneva, Switzerland

04.08.2014

Published in:

Current Biology. - 2014, vol. 24, no. 15, p. 1679–1688

English Excitatory synapses in the CNS are highly dynamic structures that can show activity- dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca²⁺ elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca²⁺ events in astrocytes and PAP morphological dynamics remain unclear.Results In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability.Conclusions This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

Faculty

Faculté des sciences et de médecine

Department

Département de Chimie

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