Optogenetics stimulates nerve reorganization in the contralesional anterolateral primary motor cortex in a mouse model of ischemic stroke.

ABSTRACT

The anterolateral motor cortex of rodents is an important motor auxiliary area, and its function is similar to that of the premotor area in humans. Activation and inhibition of the contralesional anterolateral motor cortex (cALM) have been shown to have direct effects on motor behavior. However, the significance of cALM activation and inhibition in the treatment of stroke remains unclear. This study investigated the role of optogenetic cALM stimulation in a mouse model of cerebral stroke. The results showed that 21-day optogenetic cALM inhibition, but not activation, improved neurological function. In addition, optogenetic cALM stimulation substantially altered dendritic structural reorganization and dendritic spine plasticity, as optogenetic cALM inhibition resulted in increased dendritic length, number of dendritic spines, and number of perforated synapses, whereas optogenetic activation led to an increase in the number of multiple synapse boutons and the number of dendritic intersections. Furthermore, RNA-seq analysis showed that multiple biological processes regulated by the cALM were upregulated immediately after optogenetic cALM inhibition, and that several immediate-early genes (including cFOS, Erg1, and Sema3f) were expressed at higher levels after optogenetic inhibition than after optogenetic activation. These results were confirmed by quantitative reverse transcription-polymerase chain reaction. Finally, immunofluorescence analysis showed that the c-FOS signal in layer V of the primary motor cortex in the ischemic hemisphere was higher after optogenetic cALM activation than it was after optogenetic cALM inhibition. Taken together, these findings suggest that optogenetic cALM stimulation promotes neural reorganization in the primary motor cortex of the ischemic hemisphere, and that optogenetic cALM inhibition and activation have different effects on neural plasticity. The study was approved by the Experimental Animal Ethics Committee of Fudan University (approval No. 201802173S) on March 3, 2018.