The infusion of an NMDA antagonist into perirhinal cortex suppresses amygdala-kindled seizures

The seizure-modulating role of N-methyl-D-aspartate (NMDA) receptors located in several limbic areas was investigated. Amygdala-kindled rats were microinfused with the selective NMDA-receptor antagonist 2-amino-5-phosphonovalerate (APV, 1 microliter, 70 nmol) or artificial cerebrospinal fluid (ACSF) applied through a cannula located in either the amygdala or perirhinal, pyriform or deep prepyriform cortices. APV infused into the stimulation site raised the threshold for seizure generation. Surprisingly, APV infused into perirhinal cortex, but not into other regions, also dramatically suppressed behavioural seizures and afterdischarges (AD) elicited 5 min after the infusion. If stimulus intensities were markedly elevated however, the seizure suppression was overcome. This latter effect was reversible and repeatable, as seizures and AD were reliably reinstated when these animals were stimulated after infusion with ACSF. A similar effect, whereby perirhinal infusions blocked seizure activity, was also demonstrated in an animal kindled from the olfactory bulb and in one kindled from the perforant path. These results suggest that NMDA receptors located in the perirhinal cortex may play a major role in the modulation of AD activity elicited from more distal brain regions. Furthermore, activation of perirhinal cortex may be a critical requirement for the generation of amygdala-stimulated AD in the kindled animal.