Increased threshold of short-latency motor evoked potentials in transgenic mice expressing Channelrhodopsin-2

• Published in: PloS one Vol. 12; no. 5; p. e0178803
• Main Authors: Wu, Wei, Xiong, Wenhui, Zhang, Ping, Chen, Lifang, Fang, Jianqiao, Shields, Christopher, Xu, Xiao-Ming, Jin, Xiaoming
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.05.2017; Public Library of Science (PLoS)
• Subjects: Action potential; Acupuncture; Amplitudes; Animals; Assessments; Biology; Biology and Life Sciences; Brain research; Brain stem; Channelrhodopsins; Cortex (motor); Current injection; Electric Stimulation; Electrical stimuli; Electrodes; Evoked potentials; Evoked Potentials, Motor; Excitability; Firing; Genes; Genetic aspects; Genetic engineering; Genetically modified mice; Health aspects; Injection; Laboratory animals; Latency; Magnetic fields; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Morphology; Motor evoked potentials; Motor task performance; Nervous system; Neural networks; Neurons; Neurosciences; Patch-Clamp Techniques; Pyramidal cells; Pyramidal tracts; Research and Analysis Methods; Reticulospinal tract; Reticulospinal tracts; Rhodopsin; Rodents; Surgery; Transcranial magnetic stimulation; Transcription; Transgenic animals; Transgenic mice; Traumatic brain injury; Walking; Indiana; United States > US; Indianapolis Indiana; Kentucky
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0178803

Transgenic mice that express channelrhodopsin-2 or its variants provide a powerful tool for optogenetic study of the nervous system. Previous studies have established that introducing such exogenous genes usually does not alter anatomical, electrophysiological, and behavioral properties of neurons in these mice. However, in a line of Thy1-ChR2-YFP transgenic mice (line 9, Jackson lab), we found that short-latency motor evoked potentials (MEPs) induced by transcranial magnetic stimulation had a longer latency and much lower amplitude than that of wild type mice. MEPs evoked by transcranial electrical stimulation also had a much higher threshold in ChR2 mice, although similar amplitudes could be evoked in both wild and ChR2 mice at maximal stimulation. In contrast, long-latency MEPs evoked by electrically stimulating the motor cortex were similar in amplitude and latency between wild type and ChR2 mice. Whole-cell patch clamp recordings from layer V pyramidal neurons of the motor cortex in ChR2 mice revealed no significant differences in intrinsic membrane properties and action potential firing in response to current injection. These data suggest that corticospinal tract is not accountable for the observed abnormality. Motor behavioral assessments including BMS score, rotarod, and grid-walking test showed no significant differences between the two groups. Because short-latency MEPs are known to involve brainstem reticulospinal tract, while long-latency MEPs mainly involve primary motor cortex and dorsal corticospinal tract, we conclude that this line of ChR2 transgenic mice has normal function of motor cortex and dorsal corticospinal tract, but reduced excitability and responsiveness of reticulospinal tracts. This abnormality needs to be taken into account when using these mice for related optogenetic study.