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

• 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
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bht028

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.