Degraded inferior colliculus responses to complex sounds in prenatally exposed VPA rats.

BACKGROUND: Individuals with autism spectrum disorders (ASD) often exhibit altered sensory processing and deficits in language development. Prenatal exposure to valproic acid (VPA) increases the risk for ASD and impairs both receptive and expressive language. Like individuals with ASD, rodents prenatally exposed to VPA exhibit degraded auditory cortical processing and abnormal neural activity to sounds. Disrupted neuronal morphology has been documented in earlier processing areas of the auditory pathway in VPA-exposed rodents, but there are no studies documenting early auditory pathway physiology. Therefore, the objective of this study is to characterize inferior colliculus (IC) responses to different sounds in rats prenatally exposed to VPA compared to saline-exposed rats. METHODS: In vivo extracellular multiunit recordings from the inferior colliculus were collected in response to tones, speech sounds, and noise burst trains. RESULTS: Our results indicate that the overall response to speech sounds was degraded in VPA-exposed rats compared to saline-exposed controls, but responses to tones and noise burst trains were unaltered. CONCLUSIONS: These results are consistent with observations in individuals with autism that neural responses to complex sounds, like speech, are often altered, and lays the foundation for future studies of potential therapeutics to improve auditory processing in the VPA rat model of ASD.

Degraded inferior colliculus responses to complex sounds in prenatally exposed VPA rats.

Background: Individuals with autism spectrum disorders (ASD) often exhibit altered sensory processing and deficits in language development. Prenatal exposure to valproic acid (VPA) increases the risk for ASD and impairs both receptive and expressive language. Like individuals with ASD, rodents prenatally exposed to VPA exhibit degraded auditory cortical processing and abnormal neural activity to sounds. Disrupted neuronal morphology has been documented in earlier processing areas of the auditory pathway in VPA-exposed rodents, but there are no studies documenting early auditory pathway physiology. Therefore, the objective of this study is to characterize inferior colliculus (IC) responses to different sounds in rats prenatally exposed to VPA compared to saline-exposed rats. Methods: Neural recordings from the inferior colliculus were collected in response to tones, speech sounds, and noise burst trains. Results: Our results indicate that the overall response to speech sounds was degraded in VPA-exposed rats compared saline-exposed controls, but responses to tones and noise burst trains were unaltered. Conclusions: These results are consistent with observations in individuals with autism that neural responses to complex sounds, like speech, are often altered, and lays the foundation for future studies of potential therapeutics to improve auditory processing in the VPA rat model of ASD.

Auditory Brainstem Responses Predict Behavioral Deficits in Rats with Varying Levels of Noise-Induced Hearing Loss.

Intense noise exposure is a leading cause of hearing loss, which results in degraded speech sound discrimination ability, particularly in noisy environments. The development of an animal model of speech discrimination deficits due to noise induced hearing loss (NIHL) would enable testing of potential therapies to improve speech sound processing. Rats can accurately detect and discriminate human speech sounds in the presence of quiet and background noise. Further, it is known that profound hearing loss results in functional deafness in rats. In this study, we generated rats with a range of impairments which model the large range of hearing impairments observed in patients with NIHL. One month after noise exposure, we stratified rats into three distinct deficit groups based on their auditory brainstem response (ABR) thresholds. These groups exhibited markedly different behavioral outcomes across a range of tasks. Rats with moderate hearing loss (30 dB shifts in ABR threshold) were not impaired in speech sound detection or discrimination. Rats with severe hearing loss (55 dB shifts) were impaired at discriminating speech sounds in the presence of background noise. Rats with profound hearing loss (70 dB shifts) were unable to detect and discriminate speech sounds above chance level performance. Across groups, ABR threshold accurately predicted behavioral performance on all tasks. This model of long-term impaired speech discrimination in noise, demonstrated by the severe group, mimics the most common clinical presentation of NIHL and represents a useful tool for developing and improving interventions to target restoration of hearing.