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

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.

Shank3-deficient rats exhibit degraded cortical responses to sound.

Individuals with SHANK3 mutations have severely impaired receptive and expressive language abilities. While brain responses are known to be abnormal in these individuals, the auditory cortex response to sound has remained largely understudied. In this study, we document the auditory cortex response to speech and non-speech sounds in the novel Shank3-deficient rat model. We predicted that the auditory cortex response to sounds would be impaired in Shank3-deficient rats. We found that auditory cortex responses were weaker in Shank3 heterozygous rats compared to wild-type rats. Additionally, Shank3 heterozygous responses had less spontaneous auditory cortex firing and were unable to respond well to rapid trains of noise bursts. The rat model of the auditory impairments in SHANK3 mutation could be used to test potential rehabilitation or drug therapies to improve the communication impairments observed in individuals with Phelan-McDermid syndrome. Autism Res 2018, 11: 59-68. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Individuals with SHANK3 mutations have severely impaired language abilities, yet the auditory cortex response to sound has remained largely understudied. In this study, we found that auditory cortex responses were weaker and were unable to respond well to rapid sounds in Shank3-deficient rats compared to control rats. The rat model of the auditory impairments in SHANK3 mutation could be used to test potential rehabilitation or drug therapies to improve the communication impairments observed in individuals with Phelan-McDermid syndrome.