División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Sci Rep. 2022 Dec 23;12(1):22230. doi: 10.1038/s41598-022-26402-9.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose hallmarks are social deficits, language impairment, repetitive behaviors, and sensory alterations. It has been reported that patients with ASD show differential activity in cortical regions, for instance, increased neuronal activity in visual processing brain areas and atypical visual perception compared with healthy subjects. The causes of these alterations remain unclear, although many studies demonstrate that ASD has a strong genetic correlation. An example is Phelan-McDermid syndrome, caused by a deletion of the Shank3 gene in one allele of chromosome 22. However, the neuronal consequences relating to the haploinsufficiency of Shank3 in the brain remain unknown. Given that sensory abnormalities are often present along with the core symptoms of ASD, our goal was to study the tuning properties of the primary visual cortex to orientation and direction in awake, head-fixed Shank3 mice. We recorded neural activity in vivo in response to visual gratings in the primary visual cortex from a mouse model of ASD (Shank3 mice) using the genetically encoded calcium indicator GCaMP6f, imaged with a two-photon microscope through a cranial window. We found that Shank3 mice showed a higher proportion of neurons responsive to drifting gratings stimuli than wild-type mice. Shank3 mice also show increased responses to some specific stimuli. Furthermore, analyzing the distributions of neurons for the tuning width, we found that Shank3 mice have narrower tuning widths, which was corroborated by analyzing the orientation selectivity. Regarding this, Shank3 mice have a higher proportion of selective neurons, specifically neurons showing increased selectivity to orientation but not direction. Thus, the haploinsufficiency of Shank3 modified the neuronal response of the primary visual cortex.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社交缺陷、语言障碍、重复行为和感官改变。据报道，与健康受试者相比，ASD 患者的皮质区域表现出不同的活动，例如，视觉处理脑区的神经元活动增加和异常的视觉感知。尽管许多研究表明 ASD 具有很强的遗传相关性，但这些变化的原因仍不清楚。例如，由 22 号染色体上 Shank3 基因的一个等位基因缺失引起的 Phelan-McDermid 综合征。然而，大脑中 Shank3 单倍不足与神经元后果之间的关系尚不清楚。鉴于感觉异常通常与 ASD 的核心症状同时存在，我们的目标是研究清醒、头部固定的 Shank3 小鼠大脑中初级视觉皮层对朝向和方向的调谐特性。我们使用基因编码钙指示剂 GCaMP6f 在 Shank3 小鼠（ASD 小鼠模型）的初级视觉皮层中记录活体神经活动，通过颅窗用双光子显微镜进行成像。我们发现 Shank3 小鼠对漂移光栅刺激有更高比例的神经元反应，而野生型小鼠则较少。Shank3 小鼠对一些特定刺激的反应也增加了。此外，通过分析调谐宽度的神经元分布，我们发现 Shank3 小鼠的调谐宽度较窄，这通过分析方向选择性得到了证实。关于这一点，Shank3 小鼠有更高比例的选择性神经元，特别是对方向但不对方向有更高选择性的神经元。因此，Shank3 的单倍不足改变了初级视觉皮层的神经元反应。
