Piriform cortex is a seizurogenic focus

Considerable evidence, particularly in the last five years, has spotlighted PC as a key seizurogenic site in the cerebral cortex and dysfunction of this area may play an important role in temporal lobe epilepsy. Systemic injection of muscarinic receptor agonists or acetylcholinesterase inhibitors produces robust, sustained seizure activity in PC. Several recent studies have demonstrated that PC is the first cortical or subcortical forebrain structure to exhibit increased c-fos expression, a marker for elevated neuronal activity, after convulsive doses of pilocarpine or the irreversible acetylcholinesterase 

Abbreviations PC, piriform cortex mAChR, muscarinic cholinergic receptor nAChR, nicotinic cholinergic receptor alpha and beta adrenergic receptors D, dopamine receptors 5-HT,a and S-HTj /o serotonin receptors NMDA, N-methyl-D-Aspartate receptor AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazolepropi-onic acid receptor GABAa/b, gamma aminobutyric acidreceptor XX, receptor present, receptor not present NR, receptor not present or not studied. 

Gale and colleagues (Halonen et al. 1994) have recently identified key relay sites involved in the spread of seizures triggered in deep prepyriform cortex to other forebrain structures. These studies found that microinjections of muscimol or non-NMDA receptor antagonists into posterior PC or the dorsally adjacent perirhinal cortex prevented the propagation of seizures from rostral PC. 

The role of NMDA receptors in seizure generation in PC is less clear. Microinjection of an NMDA receptor antagonist into PC was reported to prevent seizures induced by systemic injection of pilocarpine (Millan et al. 1986). However, later studies by the same group (Millan et al. 1988) found that microinjection of NMDA into PC did not increase seizure susceptibility to subconvulsive doses of pilocarpine and, paradoxically, prevented seizures induced by a convulsive dose of pilocarpine. 

Interestingly, intact afferent input to PC from the olfactory bulb appears to be required for the initiation of seizures in PC. Olfactory bulb deafferentation (bulbectomy) protects against pilocarpine-induced seizures and increases the dose of KA infused into PC necessary to produce seizures (Millan et al. 1988). 

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