title: Neuroligin-1 overexpression in newborn granule cells in vivo.
abstract: Adult-born dentate granule cells integrate into the hippocampal network, extend neurites and form synapses in otherwise mature tissue. Excitatory and inhibitory inputs innervate these new granule cells in a stereotyped, temporally segregated manner, which presents a unique opportunity to study synapse development in the adult brain. To examine the role of neuroligins as synapse-inducing molecules in vivo, we infected dividing neural precursors in adult mice with a retroviral construct that increased neuroligin-1 levels during granule cell differentiation. By 21 days post-mitosis, exogenous neuroligin-1 was expressed at the tips of dendritic spines and increased the number of dendritic spines. Neuroligin-1-overexpressing cells showed a selective increase in functional excitatory synapses and connection multiplicity by single afferent fibers, as well as an increase in the synaptic AMPA/NMDA receptor ratio. In contrast to its synapse-inducing ability in vitro, neuroligin-1 overexpression did not induce precocious synapse formation in adult-born neurons. However, the dendrites of neuroligin-1-overexpressing cells did have more thin protrusions during an early period of dendritic outgrowth, suggesting enhanced filopodium formation or stabilization. Our results indicate that neuroligin-1 expression selectively increases the degree, but not the onset, of excitatory synapse formation in adult-born neurons.
authors.affiliation: Portland VA Medical Center, Portland, Oregon, United States of America. schneler@ohsu.edu
authors.forename: Eric
authors.initials: E
authors.lastname: Schnell
authors.forename: Aesoon L
authors.initials: AL
authors.lastname: Bensen
authors.forename: Eric K
authors.initials: EK
authors.lastname: Washburn
authors.forename: Gary L
authors.initials: GL
authors.lastname: Westbrook
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D008979:Moloney murine leukemia virus / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C093438:neuroligin 1