Impaired Adaptation and Laminar Processing of the Oddball Paradigm in the Primary Visual Cortex of Fmr1 KO Mouse.

Both adaptation and novelty detection are an integral part of sensory processing. Recent animal oddball studies have advanced our understanding of circuitry underlying contextual processing in early sensory areas. However, it is unclear how adaptation and mismatch (MM) responses depend on the tuning properties of neurons and their laminar position. Furthermore, given that reduced habituation and sensory overload are among the hallmarks of altered sensory perception in autism, we investigated how oddball processing might be altered in a mouse model of fragile X syndrome (FX). Using silicon probe recordings and a novel spatial frequency (SF) oddball paradigm, we discovered that FX mice show reduced adaptation and enhanced MM responses compared to control animals. Specifically, we found that adaptation is primarily restricted to neurons with preferred oddball SF in FX compared to WT mice. Mismatch responses, on the other hand, are enriched in the superficial layers of WT animals but are present throughout lamina in FX animals. Last, we observed altered neural dynamics in FX mice in response to stimulus omissions. Taken together, we demonstrated that reduced feature adaptation coexists with impaired laminar processing of oddball responses, which might contribute to altered sensory perception in FX syndrome and autism.

适应和新奇检测都是感觉处理不可或缺的一部分。近期的动物奇异刺激研究增进了我们对早期感觉区域中情境处理相关神经回路的理解。然而，尚不清楚适应和错配（MM）反应如何取决于神经元的调谐特性及其层状位置。此外，鉴于习惯化减弱和感觉过载是自闭症中感觉感知改变的特征之一，我们研究了在脆性X综合征（FX）小鼠模型中奇异刺激处理可能如何改变。利用硅探针记录和一种新颖的空间频率（SF）奇异刺激范式，我们发现与对照动物相比，FX小鼠表现出适应减弱和MM反应增强。具体而言，我们发现与野生型（WT）小鼠相比，FX小鼠的适应主要局限于对奇异刺激空间频率有偏好的神经元。另一方面，错配反应在野生型动物的浅层富集，但在FX动物的整个层状结构中都存在。最后，我们观察到FX小鼠在刺激缺失时神经动力学发生改变。综上所述，我们证明了特征适应减弱与奇异刺激反应的层状处理受损同时存在，这可能导致FX综合征和自闭症中的感觉感知改变。