Perirhinal cortex hyperexcitability in pilocarpine‐treated epileptic rats

Abstract

The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and agematched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABA A receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy.

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

“…Such a mechanism has been reported in the hippocampus and EC layers II/III (Bekenstein and Lothman, 1993;Williams et al, 1993;Sloviter, 1987;Doherty and Dingledine, 2001;Sloviter et al, 2003;Kumar and Buckmaster, 2006). Experiments performed in pilocarpine-treated rats have also demonstrated that pharmacologically isolated, GABA A receptor-mediated IPSPs have more positive reversal potentials in neurons recorded in vitro from the epileptic subiculum, peirhinal cortex and amygdala (de Guzman et al, 2006;Benini and Avoli, 2005;Benini et al, 2011); these data often correlated with reduced levels of mRNA expression and immunoreactivity of the neuron-specific cotransporter KCC2. In line with the view that altered homeostasis of intracellular [Cl − ] is associated with epileptogenesis, NKCC1 mRNA and proteins in the mouse CA1 subfiled are up-regulated up to 45 days following pilocarpine-induced status epilepticus, while KCC2 is down-regulated (Li et al, 2008).…”

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

“…The parahippocampal gyrus, particularly the anterior entorhinal and perirhinal regions, plays an important role in the generation and propagation of temporal lobe seizures (Bernasconi et al , 2000; Wennberg et al , 2002; Bartolomei et al , 2005; Benini et al , 2011). Parahippocampal diffusion alterations have been reported in patients with TLE using DTI techniques (McDonald et al , 2008; Yogarajah et al , 2008; Ahmadi et al , 2009; Keller et al , 2012).…”

Pathophysiogenesis of Mesial Temporal Lobe Epilepsy: Is Prevention of Damage Antiepileptogenic?

“…These alterations are caused by a reduction in the expression of potassium-chloride transporter member 5 along with a decrease number of parvalbumin-positive interneurons in subiculum, perirhinal and insular cortices [63, 97, 98]. …”