Altered Inhibition in Lateral Amygdala Networks in a Rat Model of Temporal Lobe Epilepsy

Ruba Benini, Massimo Avoli
2006 Journal of Neurophysiology  
Benini, Ruba and Massimo Avoli. Altered inhibition in lateral amygdala networks in a rat model of temporal lobe epilepsy. . 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 nonepileptic controls (NECs) to shed light on the electrophysiological changes that
more » ... cur 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: 1) large amplitude depolarizing postsynaptic potentials (PSPs) and 2) 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 inhibitory PSP (IPSP) in both NECs and pilocarpine-treated tissue. The reversal potential of the early GABA A receptor-mediated component, but not of the late GABA B receptormediated 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 compared with NECs. Altogether, these findings suggest that alterations in both pre-and postsynaptic inhibitory mechanisms contribute to synaptic hyperexcitability of LA networks in epileptic rats. Address for reprint requests and other correspondence: M. Avoli, 3801 University, I. Cellular pathology of amygdala neurons in human temporal lobe epilepsy. Acta Neuropathol (Berl) 106: 99 -106, 2003. Asprodini EK, Rainnie DG, and Shinnick-Gallagher P. Epileptogenesis reduces the sensitivity of presynaptic gamma-aminobutyric acidB receptors on glutamatergic afferents in the amygdala. J Pharmacol Exp Ther 262: 1011-1021, 1992. Behr J, Gebhardt C, Heinemann U, and Mody I. Kindling enhances kainate receptor-mediated depression of GABAergic inhibition in rat granule cells. Eur J Neurosci 16: 861-867, 2002. Ben-Ari Y, Cherubini E, Corradetti R, and Gaiarsa JL. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol 416: 303-325, 1989. Benini R, D'Antuono M, Pralong E, and Avoli M. Involvement of amygdala networks in epi-leptiform synchronization in vitro. Neuroscience 120: 75-84, 2003. Callahan PM, Paris JM, Cunningham KA, and Shinnick-Gallagher P. Decrease of GABA-immunoreactive neurons in the amygdala after electrical kindling in the rat. Brain Res 555: 335-339, 1991. Cartmell J and Schoepp DD. Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem 75: 889 -907, 2000. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, and Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32: 778 -782, 1991. Cavalheiro EA, Silva DF, Turski WA, Calderazzo-Filho LS, Bortolotto ZA, and Turski L. The susceptibility of rats to pilocarpine-induced seizures is age-dependent. Brain Res 465: 43-58, 1987. Cohen I, Navarro V, Clemenceau S, Baulac M, and Miles R. On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298: 1418 -1421, 2002. Connors BW and Prince DA. Effects of local anesthetic QX-314 on the membrane properties of hippocampal pyramidal neurons. J Pharmacol Exp Ther 220: 476 -481, 1982.
doi:10.1152/jn.01217.2005 pmid:16381802 fatcat:yuba5lu7uzgrzcbkvtumucxpl4