Author: Houben, T.; Loonen, I.C.; Baca, S.M.; Schenke, M.; Meijer, J.H.; Ferrari, M.D.; Terwindt, G.M.; Voskuyl, R.A.; Charles, A.; van den Maagdenberg, A.M.; Tolner, E.A.
Description: Cortical spreading depression, which plays an important role in multiple neurological disorders, has been studied primarily with experimental models that use highly invasive methods. We developed a relatively non-invasive optogenetic model to induce cortical spreading depression by transcranial stimulation of channelrhodopsin-2 ion channels expressed in cortical layer 5 neurons. Light-evoked cortical spreading depression in anesthetized and freely behaving mice was studied with intracortical DC-potentials, multi-unit activity and/or non-invasive laser Doppler flowmetry, and optical intrinsic signal imaging. In anesthetized mice, cortical spreading depression induction thresholds and propagation rates were similar for invasive (DC-potential) and non-invasive (laser Doppler flowmetry) recording paradigms. Cortical spreading depression-related vascular and parenchymal optical intrinsic signal changes were similar to those evoked with KCl. In freely behaving mice, DC-potential and multi-unit activity recordings combined with laser Doppler flowmetry revealed cortical spreading depression characteristics comparable to those under anesthesia, except for a shorter cortical spreading depression duration. Cortical spreading depression resulted in a short increase followed by prolonged reduction of spontaneous active behavior. Motor function, as assessed by wire grip tests, was transiently and unilaterally suppressed following a cortical spreading depression. Optogenetic cortical spreading depression induction has significant advantages over current models in that multiple cortical spreading depression events can be elicited in a non-invasive and cell type-selective fashion.
Subject Headings: Action Potentials/physiology; Anesthesia; Animals; Bacterial Proteins/genetics; Behavior, Animal/physiology; Cerebrovascular Circulation/physiology; Channelrhodopsins; Cortical Spreading Depression/physiology; Female; Laser-Doppler Flowmetry; Luminescent Proteins/genetics; Male; Mice, Transgenic; Optogenetics; Photic Stimulation; Recombinant Fusion Proteins/genetics; Behavior; electrophysiology; non-invasive; optogenetics; vascular dynamics
Keywords: Optogenetic induction of cortical spreading depression in anesthetized and freely behaving mice
Publication year: 2017
Journal or book title: Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Volume: 37
Issue: 5
Pages: 1641-1655
Find the full text :Â https://journals.sagepub.com/doi/pdf/10.1177/0271678X16645113
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Type: Journal Article
Serial number: 2641