Blockade of in vitro ictogenesis by low-frequency stimulation coincides with increased epileptiform response latency

• Published in: Journal of neurophysiology Vol. 114; no. 1; pp. 21 - 28
• Main Authors: Kano, Toshiyuki, Inaba, Yuji, D'Antuono, Margherita, Biagini, Giuseppe, Levésque, Maxime, Avoli, Massimo
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.07.2015
• Series: Neurobiology of Deep Brain Stimulation
• Subjects: 4-Aminopyridine; Amygdala - drug effects; Amygdala - physiopathology; Animals; Call for Papers; Cerebral Cortex - drug effects; Cerebral Cortex - physiopathology; Disease Models, Animal; Electric Stimulation - methods; Electric Stimulation Therapy - methods; Epilepsy; GABA-B Receptor Antagonists - pharmacology; Male; Rats, Sprague-Dawley; Receptors, GABA-B - metabolism; Time Factors; Tissue Culture Techniques; repetitive stimulation; amygdala; ictogenesis; perirhinal cortex
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00248.2015

Low-frequency stimulation, delivered through transcranial magnetic or deep-brain electrical procedures, reduces seizures in patients with pharmacoresistant epilepsy. A similar control of ictallike discharges is exerted by low-frequency electrical stimulation in rodent brain slices maintained in vitro during convulsant treatment. By employing field and "sharp" intracellular recordings, we analyzed here the effects of stimuli delivered at 0.1 or 1 Hz in the lateral nucleus of the amygdala on ictallike epileptiform discharges induced by the K(+) channel blocker 4-aminopyridine in the perirhinal cortex, in a rat brain slice preparation. We found that 1) ictal events were nominally abolished when the stimulus rate was brought from 0.1 to 1 Hz; 2) this effect was associated with an increased latency of the epileptiform responses recorded in perirhinal cortex following each stimulus; and 3) both changes recovered to control values following arrest of the 1-Hz stimulation protocol. The control of ictal activity by 1-Hz stimulation and the concomitant latency increase were significantly reduced by GABAB receptor antagonism. We propose that this frequency-dependent increase in latency represents a short-lasting, GABAB receptor-dependent adaptive mechanism that contributes to decrease epileptiform synchronization, thus blocking seizures in epileptic patients and animal models.