The Optokinetic Reflex as a Tool for Quantitative Analyses of Nervous System Function in Mice: Application to Genetic and Drug-Induced Variation

The optokinetic reflex (OKR), which serves to stabilize a moving image on the retina, is a behavioral response that has many favorable attributes as a test of CNS function. The OKR requires no training, assesses the function of diverse CNS circuits, can be induced repeatedly with minimal fatigue or adaptation, and produces an electronic record that is readily and objectively quantifiable.
We describe a new type of OKR test apparatus in which computer-controlled visual stimuli and streamlined data analysis facilitate a relatively high throughput behavioral assay. We used this apparatus, in conjunction with infrared imaging, to quantify basic OKR stimulus-response characteristics for C57BL/6J and 129/SvEv mouse strains and for genetically engineered lines lacking one or more photoreceptor systems or with an alteration in cone spectral sensitivity. A second generation (F2) cross shows that the characteristic difference in OKR frequency between C57BL/6J and 129/SvEv is inherited as a polygenic trait. Finally, we demonstrate the sensitivity and high temporal resolution of the OKR for quantitative analysis of CNS drug action.
These experiments show that the mouse OKR is well suited for neurologic testing in the context of drug discovery and large-scale phenotyping programs.

视动反射（optokinetic reflex, OKR）是一种能够使运动图像在视网膜上保持稳定的行为反应，其作为中枢神经系统（Central Nervous System, CNS）功能检测手段具备诸多优良特性。该反射无需预先训练，可评估多样化的中枢神经环路功能，能够以极低的疲劳度与适应成本反复诱导，并可生成易于客观量化的电子记录。
本研究介绍了一款新型视动反射检测装置，其搭载计算机控制的视觉刺激系统与精简高效的数据分析流程，可实现相对高通量的行为学检测。研究结合红外成像技术，利用该装置对C57BL/6J、129/SvEv两种小鼠品系，以及缺失一种或多种光感受器系统、或视锥细胞光谱敏感性发生改变的基因工程小鼠品系的基础视动反射刺激-响应特征进行了量化分析。通过第二代（F2）杂交实验证实，C57BL/6J与129/SvEv小鼠间视动反射频率的特征性差异以多基因性状的方式遗传。最后，本研究验证了视动反射在中枢神经系统药物作用定量分析中的敏感性与高时间分辨率特性。
上述实验结果表明，小鼠视动反射非常适用于药物研发与大规模表型分析项目中的神经学检测场景。