NMDA processes mediate anterograde amnesia of contextual fear conditioning induced by hippocampal damage: immunization against amnesia by context preexposure.

Hippocampal lesions in rats produce both a retrograde and an anterograde amnesia of contextual fear conditioning. The present experiments examined the anterograde deficit in context conditioning. The deficit produced by electrolytic hippocampal lesions was apparent when training occurred on 7, 14, or 28 days following surgery, confirming the durability of the amnesia. The role of the hippocampus in context conditioning may be related to an NMDA (N-methyl-D-aspartate) receptor-mediated process. Both NMDA hippocampal lesions and intrahippocampal administration of an NMDA antagonist produced anterograde amnesia. Animals preexposed to the conditioning context 28 days prior to hippocampal lesioning were protected from the deficit normally produced by the lesions. Thus, the hippocampus must form a contextual representation during preexposure that is subsequently stored elsewhere. Once formed this representation of the context can be associated with an unconditional stimulus.