Selective changes in inhibition as determinants for limited hyperexcitability in the insular cortex of epileptic rats

The insular cortex (IC) is involved in the generalization of epileptic discharges in temporal lobe epilepsy (TLE), while seizures originating in IC can mimic the epileptic phenotype seen in some TLE patients. Few studies have however addressed the changes occurring in the IC in TLE animal models. Here, we analyzed the immunohistochemical and electrophysiological properties of IC networks in non-epileptic control and pilocarpine-treated epileptic rats. Neurons identified with a neuron-specific nuclear protein antibody showed similar counts in the two types of tissue but parvalbumin- and neuropeptide Y-positive interneurons were significantly decreased (parvalbumin, approx. -35%; neuropeptide Y, approx. -38%; P<0.01) in the epileptic IC. Non-adapting neurons were more frequently seen in the epileptic IC during intracellular injection of depolarizing current pulses. In addition, single-shock electrical stimuli elicited network-driven epileptiform responses in 87% of epileptic and in 22% of non-epileptic control neurons (P<0.01) but spontaneous postsynaptic potentials had similar amplitude, duration and intervals of occurrence in the two groups. Finally, pharmacologically isolated, GABAA receptor-mediated inhibitory postsynaptic potentials had more negative reversal potential (P<0.01) and higher peak conductance (P<0.05) in epileptic tissue. These data reveal moderate increased network excitability in the IC of pilocarpine-treated epileptic rats. We propose that such limited degree of hyperexcitability originates from loss of parvalbumin- and neuropeptide Y-positive interneurons that is compensated by an increased drive for GABAA receptor-mediated inhibition.