title: Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes.
abstract: Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sultan
authors.affiliation: Department of Biomedicine, Physiological Institute, University of Basel, Pestalozzistrasse 20, 4056 Basel, Switzerland.
authors.forename: Liyi
authors.initials: L
authors.lastname: Li
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moss
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Francesco
authors.initials: F
authors.lastname: Petrelli
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cassé
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Elias
authors.initials: E
authors.lastname: Gebara
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lopatar
authors.affiliation: CNRS UPR 3212, University of Strasbourg, Institute of Cellular and Integrative Neurosciences, 67084 Strasbourg, France.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Bezzi
authors.affiliation: Department of Biomedicine, Physiological Institute, University of Basel, Pestalozzistrasse 20, 4056 Basel, Switzerland.
authors.forename: Josef
authors.initials: J
authors.lastname: Bischofberger
authors.affiliation: University of Lausanne, Department of Fundamental Neurosciences, 9 rue du Bugnon, 1005 Lausanne, Switzerland. Electronic address: nicolas.toni@unil.ch.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology* / Q000648:ultrastructure; D047014:Clostridium botulinum type B / Q000235:genetics / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D027341:Excitatory Amino Acid Transporter 1; D005904:Glial Fibrillary Acidic Protein; D016194:Receptors, N-Methyl-D-Aspartate; D050600:SNARE Proteins; C493393:Slc1a3 protein, mouse; D013629:Tamoxifen; D012965:Sodium Chloride; D012694:Serine; D010751:Phosphopyruvate Hydratase