Memory disorders are probably the most common symptom after any process that disrupts normal medial temporal lobe functioning. The most severe form of disorder involves the loss of ability to form new memories (anterograde amnesia) and the loss of memories from before the damage (retrograde amnesia). Three experiments with rats are proposed which address fundamental properties of the neural mechanisms of retrograde amnesia. The first evaluates the temporal dependence of retrograde amnesia produced by nearly complete, selective hippocampal formation damage caused by multiple microinjections of N-methyl-Daspartate. Using both a between- and within-subject design, we evaluate the severity of retrograde amnesia for 4 types of information, spatial map, contextual conditioning, configural discriminations, and socially transmitted diet preference. Several intervals between training and hippocampal damage are sampled, between 1 and 64 weeks. Further, we independently test the effects of memory reactivations and subject age at the time of remote learning. Second, we compare the selectivity of the retrograde deficits with anterograde deficits for certain types of information. Anterograde amnesia affects declarative/relational/configural information and not nondeclarative/nonrelational/elemental information. Using variants of 4 tasks involving Morris water task, Pavlovian fear conditioning, socially transmitted diet preference, and transverse patterning we examine this distinction in retrograde amnesia after hippocampal damage. Third, we compare the retrograde gradients and the task specificity with different extents of hippocampal damage, using varying numbers of NMDA microinjections and colchicine dentate gyrus microinjections. The comparisons will address the hypotheses that temporal gradients in retrograde amnesia are related to the amount of spared hippocampal circuitry and that dentate gyrus circuitry contributes only at the time of initial memory acquisition. The results bear upon fundamental aspects of hippocampal dependent, long-term memory consolidation theories and will delineate a more precise role for the hippocampus formation in long-term memory.
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