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.
Key Words
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Article info
Publication history
Published online: October 07, 2013
Accepted:
August 22,
2013
Received in revised form:
August 6,
2013
Received:
June 18,
2013
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
