Submitted on November 17, 2005
Accepted on December 22, 2005
ALTERED INHIBITION IN LATERAL AMYGDALA NETWORKSIN A RAT MODEL OF TEMPORAL LOBE EPILEPSY
Ruba Benini1 and Massimo Avoli2*
1 Departments of Neurology & Neurosurgery, and of Physiology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada
2 Departments of Neurology & Neurosurgery, and of Physiology, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Dipartimento di Fisiologia Umana e Farmacologia, Universita di Roma, Rome, Italy
* To whom correspondence should be addressed. E-mail: massimo.avoli{at}mcgill.ca.
Clinical and experimental evidence indicates that the amygdala is involved in limbic seizures observed in patients with temporal lobe epilepsy. Here, we used simultaneous field and intracellular recordings from horizontal brain slices obtained from pilocarpine-treated rats and age-matched non-epileptic controls (NEC) to shed light on the electrophysiological changes that occur within the lateral nucleus (LA) of the amygdala. No significant differences in LA neuronal intrinsic properties were observed between pilocarpine-treated and NEC tissue. However, spontaneous field activity could be recorded in the LA of 21% of pilocarpine-treated slices but never from NECs. At the intracellular level, this network activity was characterized by robust neuronal firing and was abolished by glutamatergic antagonists. In addition, we could identify in all pilocarpine-treated LA neurons: (i) large amplitude depolarizing postsynaptic potentials (PSPs), and (ii) a lower incidence of spontaneous hyperpolarizing PSPs as compared with NECs. Single-shock stimulation of LA networks in the presence of glutamatergic antagonists revealed a biphasic IPSP in both NEC and pilocarpine-treated tissue. The reversal potential of the early GABAA-receptor mediated component, but not of the late GABAB-receptor mediated component, was significantly more depolarized in pilocarpine-treated slices. Furthermore, the peak conductance of both fast and late IPSP components had significantly lower values in pilocarpine-treated LA cells. Finally, paired-pulse stimulation protocols in the presence of glutamatergic antagonists revealed a less pronounced depression of the second IPSP in pilocarpine-treated slices as compared to NEC. Altogether, these findings suggest that alterations in both pre- and postsynaptic inhibitory mechanisms contribute to synaptic hyperexcitability of LA networks in epileptic rats.
