Cell type-specific contribution to the initiation of cortical spreading depolarization in the mouse

Cortical spreading depolarization (CSD) is a wave of transient depolarization in the neuronal and glial cells and plays a role in the pathophysiological process implicated in a number of diseases, including migraine aura, ischemic stroke and traumatic brain injury. Despite its clinical significance, the cellular mechanism underlying the initiation of CSD remains unclear. Since the mammalian cerebral cortex consists of excitatory pyramidal cells and diverse types of inhibitory interneurons, addressing their roles would be of primary importance in understanding CSD generation. In the current study, we showed the differential temporal dynamics of three cell types in the murine cortex upon the initiation of CSD using electrophysiological and histological analyses. Results showed upregulation of the firing rate with reduced spike-local field potential (LFP) coherence of all cell types in the slow wave range in the hemisphere ipsilateral to the CSD without affecting them in the contralateral hemisphere. Specifically, upon initiation of CSD, fast spiking (FS) interneurons were actively involved in local network activity with increased spike-LFP coherence in the gamma range and led a quasi-synchronous activation of the cortical neurons by showing a preceding increase of the firing activity over the other cell types. Histological analysis showed that these activated FS cells were localized in the cortical layers III and IV. These results highlighted the roles of the FS inhibitory interneuron and its interaction with the other types of cells upon the generation of CSD.