Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism.
Structural-functional connectivity deficits of neocortical circuits in the Fmr1 (-/y) mouse model of autism.
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DOI：
10.1126/sciadv.1500775
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发表时间：
2015-11
期刊：
影响因子：
13.6
通讯作者：
Frick A
中科院分区：
文献类型：
--
作者：
Haberl MG;Zerbi V;Veltien A;Ginger M;Heerschap A;Frick A
Fmr1 −/y小鼠新皮层的结构和功能连接表型支持自闭症的重要假设。脆性X综合征（FXS）是最常见的遗传性智力障碍，也是自闭症谱系障碍（ASD）的常见原因，其特征是感觉症状的高患病率。扰动的解剖连接的新皮层电路，导致其功能缺陷已被假设为有助于这些疾病的根本病因。我们通过探测FXS的Fmr1 −/y小鼠模型中局部和长程新皮层回路的功能和结构连接的改变来验证这一想法。为了实现这一点，我们结合了体内超高场扩散张量磁共振成像（MRI），功能性MRI和病毒示踪方法在成年小鼠。我们的研究结果表明，解剖超连接表型的初级视觉皮层（V1），但不成比例的低连接V1与其他新皮层区域。前脑前部和后部皮质下白色物质的结构完整性缺陷支持了这些结构数据。这些解剖学改变可能有助于观察到的功能解耦跨新皮层区域。因此，我们确定FXS作为一种“连接病”，提供了一个翻译模型，了解感觉处理缺陷和功能解耦的新皮质区FXS和ASD。
Structural and functional connectivity phenotype in the neocortex of Fmr1−/y mice supports a prominent hypothesis of autism. Fragile X syndrome (FXS), the most common inherited form of intellectual disability disorder and a frequent cause of autism spectrum disorder (ASD), is characterized by a high prevalence of sensory symptoms. Perturbations in the anatomical connectivity of neocortical circuits resulting in their functional defects have been hypothesized to contribute to the underlying etiology of these disorders. We tested this idea by probing alterations in the functional and structural connectivity of both local and long-ranging neocortical circuits in the Fmr1−/y mouse model of FXS. To achieve this, we combined in vivo ultrahigh-field diffusion tensor magnetic resonance imaging (MRI), functional MRI, and viral tracing approaches in adult mice. Our results show an anatomical hyperconnectivity phenotype for the primary visual cortex (V1), but a disproportional low connectivity of V1 with other neocortical regions. These structural data are supported by defects in the structural integrity of the subcortical white matter in the anterior and posterior forebrain. These anatomical alterations might contribute to the observed functional decoupling across neocortical regions. We therefore identify FXS as a “connectopathy,” providing a translational model for understanding sensory processing defects and functional decoupling of neocortical areas in FXS and ASD.