The dyslexia-associated gene DCDC2 is required for spike-timing precision in mouse neocortex

Biol Psychiatry. 2014 Sep 1;76(5):387-96. doi: 10.1016/j.biopsych.2013.08.018. Epub 2013 Oct 4.


Background: Variants in dyslexia-associated genes, including DCDC2, have been linked to altered neocortical activation, suggesting that dyslexia associated genes might play as yet unspecified roles in neuronal physiology.

Methods: Whole-cell patch clamp recordings were used to compare the electrophysiological properties of regular spiking pyramidal neurons of neocortex in Dcdc2 knockout (KO) and wild-type mice. Ribonucleic acid sequencing and reverse transcriptase polymerase chain reaction were performed to identify and characterize changes in gene expression in Dcdc2 KOs.

Results: Neurons in KOs showed increased excitability and decreased temporal precision in action potential firing. The RNA sequencing screen revealed that the N-methyl-D-aspartate receptor (NMDAR) subunit Grin2B was elevated in Dcdc2 KOs, and an electrophysiological assessment confirmed a functional increase in spontaneous NMDAR-mediated activity. Remarkably, the decreased action potential temporal precision could be restored in mutants by treatment with either the NMDAR antagonist (2R)-amino-5-phosphonovaleric acid or the NMDAR 2B subunit-specific antagonist Ro 25-6981.

Conclusions: These results link the function of the dyslexia-associated gene Dcdc2 to spike timing through activity of NMDAR.

Keywords: Dcdc2; Grin2B; dyslexia; excitability; neocortex; spike-time precision.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology
  • Action Potentials / physiology*
  • Animals
  • Dyslexia / genetics
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression
  • Membrane Potentials / physiology
  • Mice
  • Mice, Knockout
  • Microelectrodes
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neocortex / physiology*
  • Patch-Clamp Techniques
  • Phenols / pharmacology
  • Piperidines / pharmacology
  • Pyramidal Cells / physiology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Tissue Culture Techniques


  • DCDC2 protein, mouse
  • Excitatory Amino Acid Antagonists
  • Microtubule-Associated Proteins
  • NR2B NMDA receptor
  • Phenols
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Ro 25-6981
  • 2-Amino-5-phosphonovalerate