title: Synaptic Adhesion Molecules Regulate the Integration of New Granule Neurons in the Postnatal Mouse Hippocampus and their Impact on Spatial Memory.
abstract: Postnatal hippocampal neurogenesis induces network remodeling and may participate to mechanisms of learning. In turn, the maturation and survival of newborn neurons is regulated by their activity. Here, we tested the effect of a cell-autonomous overexpression of synaptic adhesion molecules on the maturation and survival of neurons born postnatally and on hippocampal-dependent memory performances. Families of adhesion molecules are known to induce pre- and post-synaptic assembly. Using viral targeting, we overexpressed three different synaptic adhesion molecules, SynCAM1, Neuroligin-1B and Neuroligin-2A in newborn neurons in the dentate gyrus of 7- to 9-week-old mice. We found that SynCAM1 increased the morphological maturation of dendritic spines and mossy fiber terminals while Neuroligin-1B increased spine density. In contrast, Neuroligin-2A increased both spine density and size as well as GABAergic innervation and resulted in a drastic increase of neuronal survival. Surprisingly, despite increased neurogenesis, mice overexpressing Neuroligin-2A in new neurons showed decreased memory performances in a Morris water maze task. These results indicate that the cell-autonomous overexpression of synaptic adhesion molecules can enhance different aspects of synapse formation on new neurons and increase their survival. Furthermore, they suggest that the mechanisms by which new neurons integrate in the postnatal hippocampus conditions their functional implication in learning and memory.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Marine
authors.initials: M
authors.lastname: Krzisch
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Fülling
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Jabinet
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Jan
authors.initials: J
authors.lastname: Armida
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Elias
authors.initials: E
authors.lastname: Gebara
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cassé
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Samia
authors.initials: S
authors.lastname: Habbas
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Volterra
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hornung
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, 9, rue du Bugnon, Lausanne, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Toni
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009483:Neuropsychological Tests; D065852:Spatial Memory / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015816:Cell Adhesion Molecules, Neuronal; D009419:Nerve Tissue Proteins; C093438:neuroligin 1; C098003:neuroligin 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: adult neurogenesis; hippocampus; plasticity; synaptic integration