Makowiecki Kalina, Garrett Andrew, Clark Vince, Graham Stuart L, Rodger Jennifer
Experimental and Regenerative Neurosciences School of Animal Biology, The University of Western Australia, Crawley WA, Australia.
Australian School Advanced Medicine Macquarie University, New South Wales, Australia.
Transl Vis Sci Technol. 2015 Apr 28;4(2):15. doi: 10.1167/tvst.4.2.15. eCollection 2015 Apr.
Visual evoked potentials (VEPs) are widely used to objectively assess visual system function in animal models of ophthalmological diseases. Although use of chronically implanted electrodes is common in longitudinal VEP studies using rodent models, reliability of recordings over time has not been assessed. We compared VEPs 1 and 7 days after electrode implantation in the adult mouse. We also examined stimulus-independent changes over time, by assessing electroencephalogram (EEG) power and approximate entropy of the EEG signal.
Stainless steel screws (600-μm diameter) were implanted into the skull overlying the right visual cortex and the orbitofrontal cortex of adult mice (C57Bl/6J, = 7). Animals were reanesthetized 1 and 7 days after implantation to record VEP responses (flashed gratings) and EEG activity. Brain sections were stained for glial activation (GFAP) and cell death (TUNEL).
Reliability analysis, using intraclass correlation coefficients, showed VEP recordings had high reliability within the same session, regardless of time after electrode implantation and peak latencies and approximate entropy of the EEG did not change significantly with time. However, there was poorer reliability between recordings obtained on different days, and a significant decrease in VEP amplitudes and EEG power. This amplitude decrease could be normalized by scaling to EEG power (within-subjects). Furthermore, glial activation was present at both time points but there was no evidence of cell death.
These results indicate that VEP responses can be reliably recorded even after a relatively short recovery period but decrease response peak amplitude over time. Although scaling the VEP trace to EEG power normalized this decrease, our results highlight that time-dependent cortical excitability changes are an important consideration in longitudinal VEP studies.
This study shows changes in VEP characteristics over time in chronically implanted mice. Thus, future preclinical longitudinal studies should consider time in addition to amplitude and latency when designing and interpreting research.
视觉诱发电位（VEP）被广泛用于客观评估眼科疾病动物模型中的视觉系统功能。尽管在使用啮齿动物模型的纵向VEP研究中，长期植入电极很常见，但尚未评估记录随时间的可靠性。我们比较了成年小鼠电极植入后1天和7天的VEP。我们还通过评估脑电图（EEG）功率和EEG信号的近似熵，研究了随时间变化的与刺激无关的变化。
将不锈钢螺钉（直径600μm）植入成年小鼠（C57Bl/6J，n = 7）右侧视觉皮层和眶额叶皮层上方的颅骨中。在植入后1天和7天对动物再次进行麻醉，以记录VEP反应（闪烁光栅）和EEG活动。对脑切片进行胶质细胞活化（GFAP）和细胞死亡（TUNEL）染色。
使用组内相关系数进行的可靠性分析表明，VEP记录在同一次实验中具有高可靠性，无论电极植入后的时间如何，EEG的峰值潜伏期和近似熵均未随时间显著变化。然而，不同日期获得的记录之间可靠性较差，并且VEP振幅和EEG功率显著降低。通过按EEG功率进行缩放（受试者内），可以使这种振幅降低正常化。此外，在两个时间点均存在胶质细胞活化，但没有细胞死亡的证据。
这些结果表明，即使在相对较短的恢复期后，也可以可靠地记录VEP反应，但反应峰值振幅会随时间降低。尽管将VEP轨迹按EEG功率进行缩放可使这种降低正常化，但我们的结果强调，在纵向VEP研究中，随时间变化的皮质兴奋性变化是一个重要的考虑因素。
本研究显示了长期植入小鼠中VEP特征随时间的变化。因此，未来的临床前纵向研究在设计和解释研究时，除了振幅和潜伏期外，还应考虑时间因素。
