THE EXPRESSION OF LTP BY AMPA AND/OR NMDA RECEPTORS IS DETERMINED BY THE EXTENT OF NMDA RECEPTORS ACTIVATION DURING THE TETANUS. Aniksztejn, Laurent, and Yehezkel Ben-Ari. INSERM U29, H[circumflex]opital de Port-Royal, 123 Bld de Port-Royal, 75014 Paris (France).
APStracts 2:0231N, 1995.
SUMMARY AND CONCLUSIONS
1) We have tested, in CA1 hippocampal slices, the hypothesis that the expression of LTP by AMPA and/or NMDA receptors depends upon the degree of NMDA receptors activation during the tetanus. 2) Slices were perfused in an ACSF containing glycine (1 [mu]M), bicuculline (5[mu]M) and a low Mg 2+ concentration (0.3 mM). To measure the AMPA and NMDA receptor mediated field EPSP (fEPSP A and fEPSP N respectively), we have used the following procedure: control fEPSP A was first measured; 6-cyano-7-nitroquinoxaline- 2,3-dione (CNQX, 10 [mu]M ) was then added and fEPSP N was evoked. CNQX was washed and once control fEPSP A was recorded, the Schaffer collaterals were tetanized at a weak or a strong intensity. The slope of fEPSP A was measured for 30-45 min followed by that of fEPSP N after the application of CNQX. 3) At a weak intensity (T W , which corresponds to a fEPSP A of around 0.3 mV of amplitude and no fEPSP N ), the tetanic stimulation generated LTP of fEPSP A (58.7 +/- 8.1% mean +/- SEM, n=9) but no significant potentiation of the fEPSP N (11.2 +/- 2.2 %, n=9). These values were significantly different (p < 0.05 ANOVA analysis, Fisher test) 4) In 9 out of 13 slices, tetanic stimulation of strong intensity (T S , intensity corresponding to a fEPSP N of around 0.3 mV of amplitude) generated LTP of fEPSP N (89.1 +/- 17.2 %) but not of fEPSP A (9.44 +/- 2.8 % ) . In the 4 remaining slices the tetani induce LTP of both fEPSP A and fEPSP N (81.7 +/- 14.7% and 101 +/- 35.6%, respectively, both values were not significantly different). 5) We then examined the effects of decreasing fEPSP N by 50 % in LTP generated by T S and T W . In the presence of 7- Chlorokynurenate 7Cl - -Kyn (6[mu]M) (n = 6), an antagonist of the allosteric glycine site of the NMDA receptors, T S generated LTP of fEPSP A (63.2 +/- 8.2 %) but not of fEPSP N (12.6 +/- 4.0 %). Both values were significantly different.T W still evoked LTP of fEPSP A but of smaller magnitude ( 29.8 +/- 6.3%, n = 8) than the one obtained in the absence of the antagonist (58.7 +/- 8.1%). Both values were significantly different. 7) The present observation suggests that: i) LTP of fEPSP A has a lower threshold than that of fEPSP N i.e. stronger activation of NMDA receptors during the tetani is required to induce LTP of fEPSP N than the one required for inducing LTP of fEPSP A ; ii) there is a bell-shaped relationship between the degree of activation of NMDA receptors during the tetani and the magnitude of LTP of the fEPSP A : tetani that generate LTP of fEPSP N have a low probability to induce LTP of fEPSP A . We suggest that AMPA and NMDA components are potentiated through 2 different presumably postsynaptic processes. 

Received 27 July 1995; accepted in final form 27 July 1995.
APS Manuscript Number J169-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.