title: Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability.
abstract: BACKGROUND
  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 Ca(2+) elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca(2+) 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.
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland. Electronic address: yann.bernardinelli@unige.ch.
authors.forename: Yann
authors.initials: Y
authors.lastname: Bernardinelli
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Jerome
authors.initials: J
authors.lastname: Randall
authors.affiliation: Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland.
authors.forename: Elia
authors.initials: E
authors.lastname: Janett
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Irina
authors.initials: I
authors.lastname: Nikonenko
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Stéphane
authors.initials: S
authors.lastname: König
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.
authors.forename: Emma Victoria
authors.initials: EV
authors.lastname: Jones
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Flores
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, Research Institute of the McGill University Health Centre, Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC H3G 1A4, Canada.
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
authors.affiliation: Department of Chemistry, University of Fribourg, Chemin du Musée 9, 1700 Fribourg, Switzerland.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bochet
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Anthony
authors.initials: A
authors.lastname: Holtmaat
authors.affiliation: Department of Basic Neurosciences, Medical School, University of Geneva, Rue Michel-Servet 1, 1211 Geneva 4, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Muller
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling; D005260:Female; D006624:Hippocampus / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D013003:Somatosensory Cortex / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D059008:Time-Lapse Imaging
chemical_list: D018094:Receptors, Metabotropic Glutamate