Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

Abstract

The hippocampus plays a primary role in temporal lobe epilepsy, a common form of partial epilepsy in adults. Recent studies, however, indicate that extrahippocampal areas such as the perirhinal and insular cortices represent important participants in this epileptic disorder. By employing field potential recordings in the in vitro 4‐aminopyridine model of temporal lobe epilepsy, we have investigated here the contribution of glutamatergic and GABAergic signaling to epileptiform activity in these structures. First, we provide evidence of epileptiform synchronicity between the perirhinal and insular cortices, and resolve some pharmacological and network mechanisms involved in sustaining the interictal‐ and ictal‐like discharges recorded there. Second, we report that in the absence of ionotropic glutamatergic transmission, GABAergic networks produce synchronous potentials that spread between the perirhinal and insular cortices. Finally, we have established that such activity is modulated by activating µ‐opioid receptors. Our findings support clinical and experimental evidence concerning the involvement of the perirhinal and insular cortex networks in temporal lobe epilepsy, and provide observations that may impact research focussing on the role of the insular cortex in nociception.

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…As illustrated in Fig. 14, the role of GABA A receptor-mediated inhibition to in vitro ictogenesis is further supported by the ability of drugs that interfere with GABAergic transmission to abolish ictal discharges induced by 4AP in several limbic structures (Avoli et al, , 1996aLopantsev and Avoli, 1998a;Benini et al, 2003;Sudbury and Avoli, 2007). Similar evidence has been reported in other in vitro models of epileptiform synchronization.…”

“…This evidence has later been confirmed in hippocampus-entorhinal cortex slices (Avoli et al, 1996a) and in brain slice preparations that included the entorhinal and perirhinal cortices (de Guzman et al, 2004) (Fig. 7A), the amygdala (Benini et al, 2003), the insular cortex (Sudbury and Avoli, 2007), or the cingulate cortex (Panuccio et al, 2009). …”

“…In addition, these glutamatergic independent interictal events are abolished by GABA A receptor antagonists (Fig. 8D) as well as by the μ-opioid receptor agonist [D-ala 2 , N-Me-Phe 4 , Gly 5 -ol]-enkephalin (DAGO) (Avoli et al, 1996a,b;Sudbury and Avoli, 2007;Panuccio et al, 2009) (Fig. 10B).…”

“…Slow interictal events induced by 4AP are minimally affected by the application of NMDA receptor antagonists, and surprisingly, continue to occur in the presence of NMDA and non-NMDA glutamatergic receptor antagonists. This type of glutamatergic-independent synchronous activity can be recorded from practically any limbic structures maintained in the brain slice (Avoli et al, 1996aBenini et al, 2003;Sudbury and Avoli, 2007;Panuccio et al, 2009) as well as in the isolated guinea pig brain (Uva et al, 2009). It has also been reported that the rate of occurrence of these GABAergic spikes are not influenced by modulating metabotropic glutamate receptor activity (Salah and Perkins, 2008).…”

“…In these experiments, CA3-driven interictal discharges disclosed by bath application of 4AP, are often restrained to the hippocampus proper only (see Section 5.1). However, following application of the GABA A receptor antagonist picrotoxin these epileptiform discharges become more robust and spread to distant areas such as the enthorinal cortex (Benini and Avoli, 2005) or even the insular cortex (Sudbury and Avoli, 2007). As illustrated in Fig.…”