SPATIAL-LEARNING WITHOUT NMDA RECEPTOR-DEPENDENT LONG-TERM POTENTIATION

HIPPOCAMPAL lesions impair spatial learning in the watermaze(1). Drugs that antagonize N-methyl-D-aspartate (NMDA)-receptor activity, which is required for long-term potentiation (LTP) at various hippocampal sy napses(2-4), block LTP and impair watermaze learning(4-6). This has le d to the hypothesis that NMDA receptors, through their involvement in LTP, may be necessary for spatial(4-11) and other forms of learning(12 ,13). We examined this hypothesis using NPC17742 5S-2-amino-4,5-(1,2-c yclohexyl)-7-phosphonoheptano acid), a potent and specific antagonist of NMDA receptors(14-17). Here we report that NPC17742 completely bloc ked dentate gyrus LTP but did not prevent normal spatial learning in r ats that had been made familiar with the general task requirements by non-spatial pretraining. Although these results do not rule out a cont ribution of NMDA-mediated dentate LTP to spatial learning, they indica te that this form of LTP is not required for normal spatial learning i n the watermaze.