Hypersynchronous ictal onset in the perirhinal cortex results from dynamic weakening in inhibition

Abstract

We obtained field, K(+) selective and "sharp" intracellular recordings from the rat entorhinal (EC) and perirhinal (PC) cortices in an in vitro brain slice preparation to identify the events occurring at interictal-to-ictal transition during 4-aminopyridine application. Field recordings revealed interictal- (duration: 1.1 to 2.2s) and ictal-like (duration: 31 to 103s) activity occurring synchronously in EC and PC; in addition, interictal spiking in PC increased in frequency shortly before the onset of ictal oscillatory activity thus resembling the hypersynchronous seizure onset seen in epileptic patients and in in vivo animal models. Intracellular recordings with K-acetate+QX314-filled pipettes in PC principal cells showed that spikes at ictal onset had post-burst hyperpolarizations (presumably mediated by postsynaptic GABAA receptors), which gradually decreased in amplitude. This trend was associated with a progressive positive shift of the post-burst hyperpolarization reversal potential. Finally, the transient elevations in [K(+)]o (up to 4.4mM from a base line of 3.2mM) - which occurred with the interictal events in PC - progressively increased (up to 7.3mM) with the spike immediately preceding ictal onset. Our findings indicate that hypersynchronous seizure onset in rat PC is caused by dynamic weakening of GABAA receptor signaling presumably resulting from [K(+)]o accumulation.

Keywords: 4-Aminopyridine; Ictogenesis; Inhibition; Perirhinal cortex; Seizure onset; [K(+)](o).