Neuroligin-1 overexpression in newborn granule cells in vivo

PLoS One. 2012;7(10):e48045. doi: 10.1371/journal.pone.0048045. Epub 2012 Oct 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cells, Cultured
  • Dendritic Spines / metabolism
  • Dendritic Spines / physiology*
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism
  • Excitatory Postsynaptic Potentials / physiology
  • Genetic Vectors / genetics
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Hippocampus / physiology
  • Immunohistochemistry
  • Mice
  • Microscopy, Confocal
  • Moloney murine leukemia virus / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synapses / metabolism
  • Synapses / physiology*
  • Time Factors
  • Transduction, Genetic

Substances

  • Cell Adhesion Molecules, Neuronal
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • neuroligin 1