Loss of Long-Lasting Potentiation Mediated by Group III mGluRs in Amygdala Neurons in Kindling-Induced Epileptogenesis

Volker Neugebauer , N. Bradley Keele , and Patricia Shinnick-Gallagher Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, Texas 77555-1031 Neugebauer, Volker, N. Bradley Keele, and Patricia Shinnick-Gallagher. Loss of long-lasting potentiation mediated by group III mGluRs in amygdala neurons in kindling-induced epileptogenesis. J. Neurophysiol. 78: 3475-3478, 1997. Long-lasting modifications of synaptic transmission can be induced in the amygdala by electrical stimulation as done in the long-term potentiation (LTP) model of learning and memory and the kindling model of epilepsy. The present study reports for the first time a long-lasting potentiation (LLP) of synaptic transmission that is induced pharmacologically by the activation of group III metabotropic glutamate receptors (mGluRs) in basolateral amygdala (BLA) neurons. In whole cell voltage-clamp mode, BLA neurons were recorded in brain slices from control rats and rats with amygdala-kindled seizures. The group III mGluR agonist L -2-amino-4-phosphonobutyrate ( L -AP4, 10 µM) induced LLP of monosynaptic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the lateral amygdala (maximum 258 ± 50% of predrug control; means ± SE) in control ( n = 7) but not in kindled neurons( n = 6). LLP was measured 15 min after the superfusion of L -AP4, lasted for >45 min, and was not accompanied by postsynaptic membrane changes. L -AP4 induced LLP was prevented by the group III mGluR antagonist (S)-2-methyl-2-amino-4-phosphonobutyrate (MAP4; 100 µM, n = 6) but not the group II mGluR antagonist (2S,3S,4S)-2-methyl-2-carboxycyclopropylglycine (MCCG; 100 µM, n = 3). LLP was not observed after superfusion of the group II mGluR agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine ( L -CCG; 1.0 and 10 µM) in either control ( n = 13) or kindled ( n = 10) neurons. If the underlying mechanisms and the functional significance of pharmacologically induced LLP are similar to those of LTP, the loss of L -AP4 induced LLP in kindled neurons may be a neurobiological correlate of learning and memory deficits in kindled animals and long-term alterations of brain functions in patients with epilepsies.