Sensory processing dysregulations as reliable translational biomarkers in SYNGAP1 haploinsufficiency
Sensory processing dysregulations as reliable translational biomarkers in SYNGAP1 haploinsufficiency
复制标题
感觉处理失调作为 SYNGAP1 单倍体不足的可靠翻译生物标志物
DOI：
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
G. Di Cristo
中科院分区：
文献类型：
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作者：
M. Carreno;Bidisha Chattopadhyaya;K. Agbogba;V. Côté;Siyan Wang;M. Lévesque;M. Avoli;J. Michaud;S. Lippé;G. Di Cristo
在与智力残疾相关的众多基因中，SYNGAP 1因其在患者中发现的功能丧失变体的频率和频率以及与其突变相关的广泛的共病疾病而脱颖而出。大多数探索Syngap 1单倍不足引起的小鼠模型病理生理学改变的研究都集中在认知问题和癫痫上，然而Syngap 1单倍不足是否以及在多大程度上改变了感觉知觉和处理尚不清楚。通过在清醒小鼠中进行EEG记录，我们确定了听觉和视觉处理的多个方面的特定改变，包括基线伽马振荡功率增加，刺激呈现后θ/伽马相位振幅耦合增加以及响应于不同感觉模态特定频率的异常神经夹带。我们还报告缺乏习惯性的重复听觉刺激和异常异常的声音检测。有趣的是，我们发现这些改变中的大多数也存在于人类患者中，因此使它们成为与SYNGAP 1/Syngap 1单倍不足相关的感觉加工改变的翻译生物标志物的强有力候选者。
Amongst the numerous genes associated with intellectual disability, SYNGAP1 stands out for its frequency and penetrance of loss-of-function variants found in patients, as well as the wide range of co-morbid disorders associated with its mutation. Most studies exploring the pathophysiological alterations caused by Syngap1 haploinsufficiency in mouse models have focused on cognitive problems and epilepsy, however whether and to what extent sensory perception and processing are altered by Syngap1 haploinsufficiency is less clear. By performing EEG recordings in awake mice, we identified specific alterations in multiple aspects of auditory and visual processing, including increased baseline gamma oscillation power, increased theta/gamma phase amplitude coupling following stimulus presentation and abnormal neural entrainment in response to different sensory modality-specific frequencies. We also report lack of habituation to repetitive auditory stimuli and abnormal deviant sound detection. Interestingly, we found that most of these alterations are present in human patients as well, thus making them strong candidates as translational biomarkers of sensory-processing alterations associated with SYNGAP1/Syngap1 haploinsufficiency.
影响因子：
13.9
作者：
Buzsáki G;Wang XJ
通讯作者：
Wang XJ
影响因子：
9.8
作者：
Hamdan, Fadi F.;Gauthier, Julie;Michaud, Jacques L.
通讯作者：
Michaud, Jacques L.
影响因子：
8.8
作者：
Hamm JP;Yuste R
通讯作者：
Yuste R