| First Author | Che A | Year | 2014 |
| Journal | Biol Psychiatry | Volume | 76 |
| Issue | 5 | Pages | 387-96 |
| PubMed ID | 24094509 | Mgi Jnum | J:245829 |
| Mgi Id | MGI:5921447 | Doi | 10.1016/j.biopsych.2013.08.018 |
| Citation | Che A, et al. (2014) The dyslexia-associated gene DCDC2 is required for spike-timing precision in mouse neocortex. Biol Psychiatry 76(5):387-96 |
| abstractText | 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. |
