Wu Liang, Mei Shuting, Yu Shan, Han Shihui, Zhang Yong Q
State Key Laboratory for Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Cereb Cortex. 2023 Oct 9;33(20):10546-10557. doi: 10.1093/cercor/bhad302.
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.
在自闭症谱系障碍患者中，已发现他们对听觉刺激的低层次特征辨别能力增强，同时还存在SHANK3（一种编码突触支架蛋白的基因）突变。然而，关于SHANK3突变是否会导致对听觉刺激低层次特征的神经处理增强，目前尚缺乏实验证据。本研究通过检测Shank3突变对犬类音高（音调频率）早期神经处理的影响，来探究这种可能性。我们使用奇偶数范式，从野生型和Shank3突变型犬类记录皮质电图，在该范式中，不同频率或概率的偏差音与其他音调（标准音）在重复序列中一起呈现。我们发现，相对于野生型犬类，Shank3突变型犬类对偏差音的早期神经反应幅度更大，并且在音调开始后100毫秒内对偏差频率变化的敏感度更高。此外，在Shank3突变型犬类中观察到的对偏差音增强的早期神经反应，与偏差音的概率无关。我们的研究结果突出了Shank3在调节对新声音的早期神经检测中的重要功能作用，并为自闭症患者非典型听觉信息处理的遗传基础提供了新的见解。
