Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, GA 30332, USA.
Atlanta VA Center for Visual and Neurocognitive Rehabilitation, Decatur, GA 30033, USA.
Cereb Cortex. 2021 Jun 10;31(7):3462-3474. doi: 10.1093/cercor/bhab025.
Sensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity. There is conflicting evidence for this hypothesis from several recent studies of transgenic mouse models of ASD; crucially, none have measured activity from identified excitatory and inhibitory neurons during simultaneous impairments of sensory perception. Here, we directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while simultaneously measuring visual perceptual behavior in CNTNAP2-/- knockout (KO) mice. We observed quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. During these perceptual impairments, stimuli evoked more firing of inhibitory neurons and less firing of excitatory neurons, with reduced neural sensitivity to contrast. In addition, pervasive 3-10 Hz oscillations in superficial cortical layers 2/3 (L2/3) of KO mice degraded predictions of behavioral performance from neural activity. Our findings show that perceptual deficits relevant to ASD may be associated with elevated cortical inhibitory activity along with diminished and aberrant excitatory population activity in L2/3, a major source of feedforward projections to higher cortical regions.
感觉障碍是自闭症谱系障碍 (ASD) 的核心特征。这些障碍会影响视觉感知，并被假设为源于皮质兴奋性和抑制性活动的失衡。最近几项关于 ASD 转基因小鼠模型的研究对这一假设提供了相互矛盾的证据；至关重要的是，在同时存在感觉感知障碍的情况下，没有一项研究测量过鉴定出的兴奋性和抑制性神经元的活动。在这里，我们在初级视觉皮层 (V1) 中直接记录了假定的兴奋性和抑制性群体尖峰放电，同时测量了 CNTNAP2-/- 敲除 (KO) 小鼠的视觉感知行为。我们观察到 KO 小鼠在视觉感知的速度、准确性和对比度敏感度方面存在定量损伤。在这些感知障碍期间，刺激引发了更多的抑制性神经元放电和更少的兴奋性神经元放电，对对比度的神经敏感性降低。此外，KO 小鼠浅层皮质层 2/3 (L2/3) 中普遍存在的 3-10 Hz 振荡降低了神经活动对行为表现的预测。我们的发现表明，与 ASD 相关的感知缺陷可能与皮质抑制活性升高有关，同时 L2/3 中的兴奋性群体活动减弱和异常，这是向更高皮质区域的前馈投射的主要来源。
