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, Brady Maher, R. S. Carraway, N. Khodaparast, R. Rennaker, J. J. LoTurco, M. P. Kilgard

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1753-1766
Number of pages14
JournalCerebral Cortex
Volume24
Issue number7
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Dyslexia
Auditory Cortex
Phonetics
Aptitude
RNA Interference
Genes
Speech Perception
Learning
Neurons
Mutation
Brain
Discrimination (Psychology)

Keywords

  • reading
  • specific language impairment
  • temporal processing
  • timing

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

Cite this

Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex. / Centanni, T. M.; Booker, A. B.; Sloan, A. M.; Chen, F.; Maher, Brady; Carraway, R. S.; Khodaparast, N.; Rennaker, R.; LoTurco, J. J.; Kilgard, M. P.

In: Cerebral Cortex, Vol. 24, No. 7, 2014, p. 1753-1766.

Research output: Contribution to journalArticle

Centanni, TM, Booker, AB, Sloan, AM, Chen, F, Maher, B, Carraway, RS, Khodaparast, N, Rennaker, R, LoTurco, JJ & Kilgard, MP 2014, 'Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex', Cerebral Cortex, vol. 24, no. 7, pp. 1753-1766. https://doi.org/10.1093/cercor/bht028
Centanni, T. M. ; Booker, A. B. ; Sloan, A. M. ; Chen, F. ; Maher, Brady ; Carraway, R. S. ; Khodaparast, N. ; Rennaker, R. ; LoTurco, J. J. ; Kilgard, M. P. / Knockdown of the dyslexia-associated gene Kiaa0319 impairs temporal responses to speech stimuli in rat primary auditory cortex. In: Cerebral Cortex. 2014 ; Vol. 24, No. 7. pp. 1753-1766.
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