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Cerebral cortex (New York, N.Y. : 1991)
Jul, 2014;24 (7): 1753-66.

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

T M Centanni, A B Booker, A M Sloan, F Chen, B J Maher, R S Carraway, N Khodaparast, R Rennaker, J J LoTurco, M P Kilgard
Author Information
  1. T M Centanni: School of Behavioral and Brain Sciences, University of Texas at Dallas.
  2. A B Booker: University of Connecticut.
  3. A M Sloan: School of Behavioral and Brain Sciences, University of Texas at Dallas.
  4. F Chen: University of Connecticut.
  5. B J Maher: University of Connecticut.
  6. R S Carraway: School of Behavioral and Brain Sciences, University of Texas at Dallas.
  7. N Khodaparast: School of Behavioral and Brain Sciences, University of Texas at Dallas.
  8. R Rennaker: School of Behavioral and Brain Sciences, University of Texas at Dallas.
  9. J J LoTurco: University of Connecticut.
  10. M P Kilgard: School of Behavioral and Brain Sciences, University of Texas at Dallas.
PMID: 23395846 DOI: 10.1093/cercor/bht028

Abstract

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.

Keywords

reading specific language impairment temporal processing timing

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Grants

  1. R01 MH056524/NIMH NIH HHS
  2. R01 DC010433/NIDCD NIH HHS
  3. R01 HD055655/NICHD NIH HHS
  4. P01 HD057853/NICHD NIH HHS
  5. HD055655/NICHD NIH HHS
  6. R01DC010433/NIDCD NIH HHS

MeSH Term

Acoustic Stimulation
Action Potentials
Anesthesia
Animals
Animals, Newborn
Auditory Cortex
Cell Adhesion Molecules
Disease Models, Animal
Dyslexia
Female
In Vitro Techniques
Male
Patch-Clamp Techniques
RNA, Small Interfering
Rats
Rats, Transgenic
Rats, Wistar
Reaction Time
Wakefulness

Chemicals

Cell Adhesion Molecules
RGD1307443 protein, rat
RNA, Small Interfering
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 7

Word Cloud

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