The Autism ProSAP1/Shank2 mouse model displays quantitative and structural abnormalities in ultrasonic vocalisations
The Autism ProSAP1/Shank2 mouse model displays quantitative and structural abnormalities in ultrasonic vocalisations
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DOI：
10.1016/j.bbr.2013.08.031
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发表时间：
2013-11-01
影响因子：
2.7
通讯作者：
Bourgeron, Thomas
中科院分区：
文献类型：
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作者：
Ey, Elodie;Torquet, Nicolas;Bourgeron, Thomas
小鼠超声发声经常被用作推断自闭症谱系障碍（ASD）患者语音交流缺陷的范例。然而，这些发声的作用以及它们的发展、结构和信息内容在很大程度上仍然是未知的。在本研究中，我们深入表征了野生型小鼠及其ProSAP1/Shank2（-/-）幼鼠和成年鼠的超声发声发射，这些幼鼠缺乏ASD中突变的突触支架蛋白。我们假设ProSAP1/Shank2（-/-）小鼠的发声行为不仅在数量上与野生型幼崽的发声行为不同，而且在时间组织和声学结构上表现出更多的定性异常。我们首先量化了超声波发声的发射率，并使用马尔可夫模型分析了发声序列的组织。我们随后测量了每个超声波发声的持续时间和峰值频率特征，以表征它们的声学结构。在野生型小鼠中，我们发现超声波发声序列的组织水平很高，这表明在这个复杂的系统中有交流功能。在它们的使用和声学结构中发现了非常有限的显著的性别相关变化，即使在成年小鼠中也是如此。在成年ProSAP1/Shank2（-/-）小鼠中，我们发现了呼叫使用和超声发声结构的异常。ProSAP1/Shank2（-/-）雄性和雌性小鼠发出的声音较少，叫声分布不同，峰值频率较低。本研究提供了一个全面的框架来表征小鼠超声发声异常，并证实ProSAP1/Shank2（-/-）小鼠是研究交流缺陷的相关模型。(C) 2013年作者。Elsevier B.V.版权所有。
Mouse ultrasonic vocalisations have been often used as a paradigm to extrapolate vocal communication defects observed in patients with autism spectrum disorders (ASD). The role of these vocalisations as well as their development, structure and informational content, however, remain largely unknown. In the present study, we characterised in depth the emission of pup and adult ultrasonic vocalisations of wild-type mice and their ProSAP1/Shank2(-/-) littermates lacking a synaptic scaffold protein mutated in ASD. We hypothesised that the vocal behaviour of ProSAP1/Shank2(-/-) mice not only differs from the vocal behaviour of their wild-type littermates in a quantitative way, but also presents more qualitative abnormalities in temporal organisation and acoustic structure. We first quantified the rate of emission of ultrasonic vocalisations, and analysed the organisation of vocalisations sequences using Markov models. We subsequently measured duration and peak frequency characteristics of each ultrasonic vocalisation, to characterise their acoustic structure. In wild-type mice, we found a high level of organisation in sequences of ultrasonic vocalisations, suggesting a communicative function in this complex system. Very limited significant sex-related variations were detected in their usage and acoustic structure, even in adult mice. In adult ProSAP1/Shank2(-/-) mice, we found abnormalities in the call usage and the structure of ultrasonic vocalisations. Both ProSAP1/Shank2(-/-) male and female mice uttered less vocalisations with a different call distribution and at lower peak frequency in comparison with wild-type littermates. This study provides a comprehensive framework to characterise abnormalities of ultrasonic vocalisations in mice and confirms that ProSAP1/Shank2(-/-) mice represent a relevant model to study communication defects. (C) 2013 The Authors. Published by Elsevier B.V. All rights reserved.