Seizure-like discharges induced by 4-aminopyridine in the olfactory system of the in vitro isolated guinea pig brain

Purpose: The study of the interactions leading to network- or region-specific propagation of seizures is crucial to understand ictogenesis. We have recently found that systemic (arterial) application of the potassium channel blocker, 4-aminopyridine (4AP), induces different and independent seizure activities in olfactory and in limbic structures. Here, we have characterized the network and cellular features that support 4AP-induced seizure-like events in the olfactory cortex.

Methods: Simultaneous extracellular recordings were performed from the piriform cortex, the entorhinal cortex, the olfactory tubercle, and the amygdala of the in vitro isolated guinea pig brain preparation. Intracellular, sharp electrode recordings were obtained from neurons of different layers of the region of ictal onset, the piriform cortex. Seizure-like discharges were induced by both arterial perfusion and local intracortical injections of 4AP.

Key findings: Arterial application of 4AP induces independent seizure activities in limbic and olfactory cortices. Both local applications of 4AP and cortico-cortical disconnections demonstrated that region-specific seizure-like events initiated in the primary olfactory cortex and propagate to anatomically related areas. Seizures induced by arterial administration of 4-AP are preceded by runs of fast activity at circa 30-40 Hz and are independently generated in the hemispheres. Simultaneous extracellular and intracellular recordings in the piriform cortex revealed that the onset of seizure correlates with (1) a gradual amplitude increase of fast activity runs, (2) a large intracellular depolarization with action potential firing of superficial layer neurons, and (3) no firing in a subpopulation of deep layers neurons. During the ictal event, neuronal firing was abolished for 10-30 s in all neurons and gradually restored and synchronized before seizure termination.

Significance: Our data show that olfactory neuronal networks sustain the generation of seizure-like activities that are independent from those observed in adjacent and connected limbic cortex regions. The data support the concept that functionally and anatomically hard-wired networks generate region-specific seizure patterns that could be substrates for system epilepsy.