Shank3 mutations enhance early neural responses to deviant tones in dogs

Abstract

Both enhanced discrimination of low-level features of auditory stimuli and mutations of SHANK3 (a gene that encodes a synaptic scaffolding protein) have been identified in autism spectrum disorder patients. However, experimental evidence regarding whether SHANK3 mutations lead to enhanced neural processing of low-level features of auditory stimuli is lacking. The present study investigated this possibility by examining effects of Shank3 mutations on early neural processing of pitch (tone frequency) in dogs. We recorded electrocorticograms from wild-type and Shank3 mutant dogs using an oddball paradigm in which deviant tones of different frequencies or probabilities were presented along with other tones in a repetitive stream (standards). We found that, relative to wild-type dogs, Shank3 mutant dogs exhibited larger amplitudes of early neural responses to deviant tones and greater sensitivity to variations of deviant frequencies within 100 ms after tone onsets. In addition, the enhanced early neural responses to deviant tones in Shank3 mutant dogs were observed independently of the probability of deviant tones. Our findings highlight an essential functional role of Shank3 in modulations of early neural detection of novel sounds and offer new insights into the genetic basis of the atypical auditory information processing in autism patients.