Increased dentate gyrus excitability in neuroligin-2-deficient mice in vivo

Cereb Cortex. 2011 Feb;21(2):357-67. doi: 10.1093/cercor/bhq100. Epub 2010 Jun 7.


The postsynaptic adhesion protein neuroligin-2 (NL2) is selectively localized at inhibitory synapses. Here, we studied network activity in the dentate gyrus of NL2-deficient mice following perforant path (PP) stimulation in vivo. We found a strong increase in granule cell (GC) excitability. Furthermore, paired-pulse inhibition (PPI) of the population spike, a measure for γ-aminobutyric acid (GABA)ergic network inhibition, was severely impaired and associated with reduced GABA(A) receptor (GABA(A)R)-mediated miniature inhibitory postsynaptic currents recorded from NL2-deficient GCs. In agreement with these functional data, the number of gephyrin and GABA(A)R clusters was significantly reduced in the absence of NL2, indicating a loss of synaptic GABA(A)Rs from the somata of GCs. Computer simulations of the dentate network showed that impairment of perisomatic inhibition is able to explain the electrophysiological changes observed in the dentate circuitry of NL2 knockout animals. Collectively, our data demonstrate for the first time that deletion of NL2 increases excitability of cortical neurons in the hippocampus of intact animals, most likely through impaired GABA(A)R clustering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / genetics
  • Action Potentials / physiology*
  • Animals
  • Animals, Newborn
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules, Neuronal / deficiency*
  • Computer Simulation
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology*
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Postsynaptic Potentials / genetics*
  • Gene Expression Regulation / genetics
  • In Vitro Techniques
  • Inhibition, Psychological
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Models, Neurological
  • Nerve Tissue Proteins / deficiency*
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Receptors, GABA-A / metabolism
  • Sodium Channel Blockers / pharmacology
  • Statistics, Nonparametric
  • Tetrodotoxin / pharmacology
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism


  • Carrier Proteins
  • Cell Adhesion Molecules, Neuronal
  • Excitatory Amino Acid Agonists
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Receptors, GABA-A
  • Sodium Channel Blockers
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • gephyrin
  • neuroligin 2
  • Tetrodotoxin
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-amino-5-phosphopentanoic acid
  • Valine