Involvement of AMPA receptors in CSD-induced impairment of LTP in the hippocampus.

Objective: To investigate the alteration of hippocampal long-term plasticity and basal synaptic transmission induced by repetitive cortical spreading depressions (CSDs).

Background: There is a relationship between migraine aura and amnesia attack. CSD, a state underlying migraine attacks, may be responsible for hippocampus-related symptoms. However, the precise role of CSD on hippocampal activity has not been investigated.

Methods: 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 electrophysiological studies.

Results: Repetitive CSDs led to a decrease in the magnitude of long-term potentiation in the hippocampus. CSD also reduced hippocampal synaptic efficacy, as shown by a reduction in post-synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses. In contrast, the post-synaptic N-methyl-d-aspartate receptor responses remained unchanged. In addition, there were no changes in paired-pulse profiles between the groups, indicating that CSD did not induce any presynaptic alterations.

Conclusion: These findings suggest that a reduction of post-synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor responses is the mechanism responsible for impaired hippocampal long-term potentiation induced by CSD.