Evidence for postsynaptic induction and expression of NMDA receptor independent LTP. Lawrence M. Grover. Department of Physiology, Marshall University School of Medicine, Huntington, WV 25755-9340
APStracts 4:346N, 1997.
ABSTRACT
Whole cell/patch clamp and extracellular field potential recordings were used to study the induction and expression of NMDA receptor independent LTP in area CA1 of the in vitro rat hippocampus. Induction of N-methyl-D-aspartate (NMDA) receptor independent long-term potentiation (LTP) was prevented by manipulations which inhibited postsynaptic depolarization during tetanic stimulation: direct hyperpolarization of postsynaptic neurons, and bath application of an _à_-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate receptor antagonist. NMDA receptor independent LTP was also blocked by intracellular application of the lidocaine derivative, QX-314, to CA1 pyramidal neurons. These results complement the previous findings that NMDA receptor independent LTP is inhibited by postsynaptic injections of the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; Grover and Teyler 1990), and is also inhibited by an L-type voltage- dependent calcium channel antagonist (nifedipine; Grover and Teyler 1990; Cavus and Teyler 1996). Collectively, these data make a strong case for the postsynaptic induction of this form of LTP. This paper also provides evidence for postsynaptic expression of NMDA receptor independent LTP. In an experiment where AMPA and NMDA receptor mediated EPSPs were isolated pharmacologically, LTP was found for only the AMPA receptor mediated EPSPs. In a separate experiment, paired-pulse facilitation (PPF) was measured during NMDA receptor independent LTP. Although there was an initial decrease in PPF, suggesting a posttetanic increase in the probability of glutamate release, the change in PPF decayed within 30-40 min of the tetanic stimulation, while the magnitude of the LTP was constant over this same time period. In addition, the LTP, but not the corresponding change in PPF, was blocked by the metabotropic glutamate receptor (mGluR) antagonist (ñ)-_à_-methyl-4-carboxyphenylglycine (MCPG). These results are most easily accounted for by a selective increase in postsynaptic AMPA receptor function, but one type of presynaptic modification -- an increase in the number of release sites without an overall change in the probability of release -- could also account for these results (assuming that the level of glutamate release prior to LTP induction fully saturated NMDA, but not AMPA, receptors). One possible presynaptic modification, an increase in axon excitability, was ruled out by analysis of the presynaptic fiber volley, which was not increased at any time following LTP induction. 

Received 10 April 1997; accepted in final form 24 November 1997.
APS Manuscript Number J289-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 December 1997