COMPARING LONG-TERM DEPRESSION WITH PHARMACOLOGICALLY INDUCED SYNAPTIC ATTENUATIONS IN YOUNG-RAT HIPPOCAMPI

Field excitatory postsynaptic potentials (EPSPs) were recorded in the CA1 region of hippocampal slices from 12-18-day-old rats. The isolated N-methyl-D-aspartate (NMDA) receptor mediated field EPSP as well as t he composite field EPSP of both NMDA and alpha-amino-3-hydroxy-5-methy lisoxazolepropionic acid (AMPA) receptor mediated components were obta ined in low Mg2+ solutions with 10 mu M or 1 mu M of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), respectively. The isolated AMPA receptor mediated held EPSP was obtained either in normal Mg2+ solution or in a low Mg2+ solution in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid. The wave forms of the field EPSPs were studied and the effect of long-term depr ession (LTD) on these waveforms was compared with the effects of sever al pharmacological agents that attenuate the synaptic efficacy. It was shown that LTD occurred without changes in the waveforms of isolated AMPA and NMDA EPSPs. Reducing the number of release sites by lowering the stimulus strength or reducing the probability of transmitter relea se by an adenosine agonist N-6-cyclohexyladenosine both mimicked the L TD-induced changes. Partial blockade of the AMPA receptors was also wi thout effect on the waveforms of isolated AMPA EPSPs. In contrast, par tial blockade of the NMDA receptors in several different ways resulted in waveform changes. A similar result could be inferred from experime nts using composite field EPSPs. The synaptic attenuation caused by a partial blockade of NMDA receptors therefore appears to differ mechani stically from that involved in LTD, arguing against a postsynaptic loc us of the modification involved in LTD. However, directly testing for alterations in transmitter release using the open channel blacker of N MDA receptors MK-801 failed in revealing such presynaptic changes duri ng LTD. Our results therefore suggest that LTD might be due to a coord inated pre- and postsynaptic change instead of distinct pre- or postsy naptic modifications. (C) 1997 Wiley-Liss, Inc.