Degraded neural and behavioral processing of speech sounds in a rat model of Rett syndrome

Neurobiol Dis. 2015 Nov:83:26-34. doi: 10.1016/j.nbd.2015.08.019. Epub 2015 Aug 28.

Abstract

Individuals with Rett syndrome have greatly impaired speech and language abilities. Auditory brainstem responses to sounds are normal, but cortical responses are highly abnormal. In this study, we used the novel rat Mecp2 knockout model of Rett syndrome to document the neural and behavioral processing of speech sounds. We hypothesized that both speech discrimination ability and the neural response to speech sounds would be impaired in Mecp2 rats. We expected that extensive speech training would improve speech discrimination ability and the cortical response to speech sounds. Our results reveal that speech responses across all four auditory cortex fields of Mecp2 rats were hyperexcitable, responded slower, and were less able to follow rapidly presented sounds. While Mecp2 rats could accurately perform consonant and vowel discrimination tasks in quiet, they were significantly impaired at speech sound discrimination in background noise. Extensive speech training improved discrimination ability. Training shifted cortical responses in both Mecp2 and control rats to favor the onset of speech sounds. While training increased the response to low frequency sounds in control rats, the opposite occurred in Mecp2 rats. Although neural coding and plasticity are abnormal in the rat model of Rett syndrome, extensive therapy appears to be effective. These findings may help to explain some aspects of communication deficits in Rett syndrome and suggest that extensive rehabilitation therapy might prove beneficial.

Keywords: Auditory processing; Cortex; Mecp2; Plasticity; Rett syndrome; Speech therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Cortex / physiopathology*
  • Auditory Perception / physiology*
  • Discrimination, Psychological / physiology
  • Disease Models, Animal
  • Evoked Potentials, Auditory
  • Female
  • Gene Knockout Techniques
  • Methyl-CpG-Binding Protein 2 / genetics
  • Neurons / physiology*
  • Noise
  • Phonetics*
  • Rats
  • Rats, Sprague-Dawley
  • Rett Syndrome / genetics
  • Rett Syndrome / physiopathology*

Substances

  • Mecp2 protein, mouse
  • Methyl-CpG-Binding Protein 2