Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex

One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phone...

Full description

Saved in:
Bibliographic Details
Published in:Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2014-07, Vol.24 (7), p.1753-1766
Main Authors: Centanni, T M, Booker, A B, Sloan, A M, Chen, F, Maher, B J, Carraway, R S, Khodaparast, N, Rennaker, R, LoTurco, J J, Kilgard, M P
Format: Article
Language:English
Subjects:
Acoustic Stimulation - methods
Action Potentials - genetics
Action Potentials - physiology
Anesthesia
Animals
Animals, Newborn
Auditory Cortex - metabolism
Auditory Cortex - physiology
Cell Adhesion Molecules - deficiency
Cell Adhesion Molecules - genetics
Disease Models, Animal
Dyslexia - genetics
Dyslexia - physiopathology
Female
In Vitro Techniques
Male
Patch-Clamp Techniques
Rats
Rats, Transgenic
Rats, Wistar
Reaction Time - genetics
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Wakefulness
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:One in 15 school age children have dyslexia, which is characterized by phoneme-processing problems and difficulty learning to read. Dyslexia is associated with mutations in the gene KIAA0319. It is not known whether reduced expression of KIAA0319 can degrade the brain's ability to process phonemes. In the current study, we used RNA interference (RNAi) to reduce expression of Kiaa0319 (the rat homolog of the human gene KIAA0319) and evaluate the effect in a rat model of phoneme discrimination. Speech discrimination thresholds in normal rats are nearly identical to human thresholds. We recorded multiunit neural responses to isolated speech sounds in primary auditory cortex (A1) of rats that received in utero RNAi of Kiaa0319. Reduced expression of Kiaa0319 increased the trial-by-trial variability of speech responses and reduced the neural discrimination ability of speech sounds. Intracellular recordings from affected neurons revealed that reduced expression of Kiaa0319 increased neural excitability and input resistance. These results provide the first evidence that decreased expression of the dyslexia-associated gene Kiaa0319 can alter cortical responses and impair phoneme processing in auditory cortex.
ISSN:1047-3211
1460-2199
DOI:10.1093/cercor/bht028