Kindling of claustrum and insular cortex: comparison to perirhinal cortex in the rat

Abstract

The perirhinal cortex has recently been implicated in the kindling of limbic generalized seizures. The following experiments in rats tested the selectivity of the perirhinal cortex's epileptogenic properties by comparing its kindling profile with those of the adjacent insular cortex, posterior (dorsolateral) claustrum and amygdala. The first experiment examined the kindling and EEG profiles, and found that both the claustrum and insular cortex demonstrated rapid epileptogenic properties similar to the perirhinal cortex, including very rapid kindling rates and short latencies to convulsion. Furthermore, electrical stimulation of all three structures led to a two-phase progression through stage-5 seizures which had characteristics of both neocortical and amygdaloid kindling. In a second experiment rats were suspended in a harness to allow for more detailed documentation of both forelimb and hindlimb convulsions. With this procedure we were able to detect subtle yet unique differences in convulsion characteristics from each of the kindled sites and stage-5 seizure phases. Some of these convulsive parameters were correlated with changes in FosB/DeltaFosB protein and BDNF mRNA expression measured two hours after the last convulsion. Overall, it appears that the perirhinal cortex is not unique in its property of rapid epileptogenesis. Moreover, the posterior claustrum exhibited the fastest kindling and most vigorous patterns of clonus, suggesting that it may be even more intimately associated with the motor substrates responsible for limbic seizure generalization than is the perirhinal cortex.

Epileptiform synchronization in the rat insular and perirhinal cortices in vitro

“…Given these trends, the PC has been proposed to be part of a pathway that amplifies and rapidly propagates seizure activity to motor and 13 cortical areas, giving rise to secondary generalized convulsive seizures (Kelly and Mclntyre, 1996;Mclntyre and Kelly, 2000). Interestingly, studies that compared kindling rates among the PC and the IC demonstrated similar kindling profiles (Kodama et aL, 2001;Mohapel et aL, 2001) implying that the IC may also be hyperexcitable and important in producing kindled seizures.…”

“…In addition, PC kindling produces generalized motor seizures after relatively few stimulation trials, implying that it acts as a primary route for seizure propagation from limbic to neocortical structures Kelly and Mclntyre, 1996;Sato et al, 1998;Barnes et al, 2005). Interestingly, the IC exhibits comparable kindling rates to the PC, and presents similar EEG profiles during kindled seizures (Kodama et al, 2001;Mohapel et al, 2001). Furthermore, the RAIC is a principle target for PC efferents (Delatour and Witter, 2002).…”

“…Kindling rate, the number of stimulation trials required to produce full motor seizures, has often been used as an assessment of the importance of a structure in seizure-generating circuits (Kelly and Mclntyre, 1996;Morimoto et al, 2004). The PC has been shown in numerous cases to be the fastest to kindle among ail structures tested, and with extremely short latencies between stimulus delivery and motor convulsion Mohapel et al, 1996;Sato et al, 1998;Mohapel et aL, 2001;Barnes et al, 2005; for recent reviews see Kelly and Mclntyre, 1996;Mclntyre and Kelly, 2000). Further, les ions in the PC prevent the development of kindled seizures, lending more support for its importance in epileptogenesis (Kelly and Mclntyre, 1996;Mclntyre and Kelly, 2000).…”

Impaired Activation of CA3 Pyramidal Neurons in the Epileptic Hippocampus

“…Volume 7,2005 in neuronal populations that are activated by seizures (Morris et al, 2000;Mohapel et al, 2001). Hippocampal-EC slices close to those studied in the IOS experiments were immunostained with two different FosB/∆FosB antibodies and analyzed 3 wk after pilocarpine (n = 28) or saline (n = 19) injection.…”

“…In particular, we studied hippocampal-EC slices employing intrinsic optical signal (IOS) imaging that provides information on the spatiotemporal patterns of neuronal activity (MacVicar and Hochman, 1991;Andrew et al, 1996;Jarvis et al, 1999;Weissinger et al, 2005) and thus can be used to monitor the onset and propagation of epileptiform synchronization (D'Arcangelo et al, 2001(D'Arcangelo et al, , 2005. In addition, taking advantage of FosB/∆FosB-related protein induction in neurons participating to seizures (Morris et al, 2000;Mohapel et al, 2001), we compared the in vitro findings with the ex vivo patterns of network activity identified in pilocarpine-treated epileptic rats. Both techniques provided evidence for functional downregulation of the CA3 subfield, although other hippocampal regions appeared to be hyperactive.…”