Effect of cortical spreading depression on synaptic transmission in rat hippocampus

Abstract

There is a relationship between migraine aura and amnesic attack. Cortical spreading depression (CSD), a phenomenon underlying migraine attack, may be responsible for hippocampus-related symptoms. However, the precise role of CSD on hippocampal activity has not been examined. The present study aimed to investigate the alteration of hippocampal synaptic plasticity and basal synaptic transmission induced by CSD. Furthermore, this study also aimed to examine whether capsaicin could modulate hippocampal plasticity that was altered by CSD. Male Wistar rats were divided into CSD and control groups. Repetitive CSDs were induced in vivo by topical application of solid KCl. Forty-five minutes later, the ipsilateral hippocampus was removed, and hippocampal slices were prepared for a series of in vitro electrophysiological studies. After CSD induction, SD waves also appeared in the hippocampus. Repetitive CSDs led to a decrease in the magnitude of long-term potentiation (LTP) in the hippocampus. CSD also reduced hippocampal synaptic efficacy, as shown by a reduction of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor responses. In contrast, postsynaptic N-methyl-D-aspartate (NMDA) receptor responses remained unchanged. Furthermore, there were no changes in paired-pulse profiles between the groups, indicating that CSD did not induce any presynaptic alterations. Despite unaltered NMDA receptor responses, CSD elevated the ratio of GluN2A to GluN2B subunit of NMDA receptor (Glu2A/B ratio). Moreover, capsaicin administration recovered LTP that was suppressed by CSD. These findings suggest that a reduction of postsynaptic AMPA receptor responses and an increase of Glu2A/B ratio are the mechanisms responsible for impaired hippocampal LTP induced by CSD. This impaired LTP could be improved by capsaicin.