Unilateral cortical spreading depression affects sleep need and induces molecular and electrophysiological signs of synaptic potentiation in vivo.

Cortical spreading depression (CSD) is an electrophysiological phenomenon first described by Leao in 1944 as a suppression of spontaneous electroencephalographic activity, traveling across the cerebral cortex. In vitro studies suggest that CSD may induce synaptic potentiation. One recent study also found that CSD is followed by a non-rapid eye movement (NREM) sleep duration increase, suggesting an increased need for sleep. Recent experiments in animals and humans show that the occurrence of synaptic potentiation increases subsequent sleep need as measured by larger slow wave activity (SWA) during NREM sleep, prompting the question whether CSD can affect NREM SWA. Here, we find that, in freely moving rats, local CSD induction increases corticocortical evoked responses and strongly induces brain derived neurotrophic factor (BDNF) in the affected cortical hemisphere but not in the contralateral one, consistent with synaptic potentiation in vivo. Moreover, for several hours after CSD, large slow waves occur in the affected hemisphere during rapid eye movement sleep and quiet waking but disappear during active exploration. Finally, we find that CSD increases NREM sleep duration and SWA, the latter specifically in the affected hemisphere. These effects are consistent with an increase in synaptic strength triggered by CSD, although nonphysiological phenomena associated with CSD may also play a role.