Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome.
Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome.
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DOI：
10.1186/s11689-023-09496-8
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发表时间：
2023-07-29
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
--
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自闭症谱系障碍（ASD）包括一系列使人衰弱的症状，包括感觉功能障碍和语言发育迟缓。听觉时间加工对言语感知和语言发展至关重要。时间加工的异常发展可能是与ASD相关的语言障碍的原因。很少有人知道的时间处理的发展，在任何动物模型的ASD。在目前的研究中，我们量化了在脆性X综合征（FXS）的Fmr 1基因敲除（KO）小鼠模型中整个发育过程中的听觉时间处理，FXS是智力残疾和ASD相关行为的主要遗传原因。在清醒和自由活动的野生型（WT）和KO小鼠，使用硬膜外电极，我们记录了听觉事件相关电位（ERP）和听觉时间处理的间隙噪声听觉稳态反应（Gap-ASSR）的范例。在横截面设计中记录了三个不同年龄的小鼠：出生后（p）21，p30和p60。录音从听觉和额叶皮质获得。gap-ASSR需要潜在的神经发生器来同步对嵌入噪声中的不同宽度的间隙的响应，从而提供跨基因型和年龄组的时间处理的客观测量。我们目前的证据表明，额叶，但不是听觉，皮层显示出显着的时间处理赤字在p21和p30，与穷人的能力，相位锁定到快速的差距噪音。成年小鼠的两种基因型的时间处理相似。在Fmr 1 KO小鼠的听觉和额叶皮层中，ERP幅度更大，与FXS人类的ERP数据一致。这些数据表明，在Fmr 1基因敲除小鼠的时间处理发展的皮质区域特异性延迟。额叶皮层跟踪声音快速变化的能力的发育延迟可能会形成FXS的语言延迟，更广泛地说，在ASD中。
Autism spectrum disorders (ASD) encompass a wide array of debilitating symptoms, including sensory dysfunction and delayed language development. Auditory temporal processing is crucial for speech perception and language development. Abnormal development of temporal processing may account for the language impairments associated with ASD. Very little is known about the development of temporal processing in any animal model of ASD. In the current study, we quantify auditory temporal processing throughout development in the Fmr1 knock-out (KO) mouse model of Fragile X Syndrome (FXS), a leading genetic cause of intellectual disability and ASD-associated behaviors. Using epidural electrodes in awake and freely moving wildtype (WT) and KO mice, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (gap-ASSR) paradigm. Mice were recorded at three different ages in a cross sectional design: postnatal (p)21, p30 and p60. Recordings were obtained from both auditory and frontal cortices. The gap-ASSR requires underlying neural generators to synchronize responses to gaps of different widths embedded in noise, providing an objective measure of temporal processing across genotypes and age groups. We present evidence that the frontal, but not auditory, cortex shows significant temporal processing deficits at p21 and p30, with poor ability to phase lock to rapid gaps in noise. Temporal processing was similar in both genotypes in adult mice. ERP amplitudes were larger in Fmr1 KO mice in both auditory and frontal cortex, consistent with ERP data in humans with FXS. These data indicate cortical region-specific delays in temporal processing development in Fmr1 KO mice. Developmental delays in the ability of frontal cortex to follow rapid changes in sounds may shape language delays in FXS, and more broadly in ASD.
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