Cortical pain induced by optogenetic cortical spreading depression: from whole brain activity mapping

BACKGROUND: Cortical spreading depression (CSD) is an electrophysiological event underlying migraine aura. Traditional CSD models are invasive and often cause injuries. The aim of the study was to establish a minimally invasive optogenetic CSD model and identify the active networks after CSD using whole-brain activity mapping. METHODS: CSD was induced in mice by light illumination, and their periorbital thresholds and behaviours in the open field, elevated plus-maze and light-aversion were recorded. Using c-fos, we mapped the brain activity after CSD. The whole brain was imaged, reconstructed and analyzed using the Volumetric Imaging with Synchronized on-the-fly-scan and Readout technique. To ensure the accuracy of the results, the immunofluorescence staining method was used to verify the imaging results. RESULTS: The optogenetic CSD model showed significantly decreased periorbital thresholds, increased facial grooming and freezing behaviours and prominent light-aversion behaviours. Brain activity mapping revealed that the somatosensory, primary sensory, olfactory, basal ganglia and default mode networks were activated. However, the thalamus and trigeminal nucleus caudalis were not activated. CONCLUSIONS: Optogenetic CSD model could mimic the behaviours of headache and photophobia. Moreover, the optogenetic CSD could activate multiple sensory cortical regions without the thalamus or trigeminal nucleus caudalis to induce cortical pain.