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.
APStracts 4:207N, 1997.
ABSTRACT
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 which 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 æM) induced LLP of monosynaptic EPSCs evoked by electrical stimulation in the lateral amygdala (maximum 258ñ50 % of predrug control) 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 æM, n=6) but not the group II mGluR antagonist (2S,3S,4S)-2-methyl-2-carboxycyclopropyl)glycine (MCCG; 100 æM, 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 æM) 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. 

Received 21 April 1997; accepted in final form 22 August 1997.
APS Manuscript Number J318-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997