Recent accounts suggest that the hippocampal system critically supports two central characteristics of episodic memory: the ability to establish and maintain representations for the salient relationships between experienced events (relational representation) and the capacity to flexibly manipulate memory (flexible memory expression). To test this proposal in monkeys, intact controls and subjects with bilateral aspiration lesions of the entorhinal cortex were trained postoperatively on two standard memory tasks, delayed nonmatchingto-sample (DNMS) and two-choice object discrimination (OD) learning, and three procedures intended to emphasize relational representation and flexible memory expression: a paired associate (PA) task, a transitive inference (TI) test of learning and memory for hierarchical stimulus relationships, and a spatial delayed recognition span (SDRS) procedure. The latter assessments each included critical "probe" tests that asked monkeys to evaluate the relationships among previously learned stimuli presented in novel combinations. Subjects with entorhinal cortex lesions scored as accurately as controls on all phases of DNMS and OD, procedures that can be solved on the basis of memory for individual stimuli. In contrast, experimental monkeys displayed deficits relative to controls on all phases of the PA, TI, and SDRS tasks that emphasized the flexible manipulation of memory for the relationships between familiar items. Together, the findings support the conclusion that the primate hippocampal system critically enables the relational organization of declarative memory.

We have recently suggested that certain effects of perirhinal cortex removals in monkeys can be attributed to the lesion compromising complex configural representations of visual stimuli. On this view, monkeys with perirhinal cortex lesions will be impaired on acquisition of discrimination problems that possess high "feature ambiguity," that is, those in which many of the same features belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous problems includes "configural" discrimination problems in which all features are ambiguous. In the present study, we tested control monkeys and monkeys with bilateral lesions of perirhinal cortex on a configural discrimination problem, the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using complex 2-dimensional visual stimuli. In addition, we investigated the effects of lesions to another structure that has been implicated in configural learning, the hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were facilitated, on acquisition of the transverse-patterning task. These data do not provide support for mass action theories of medial temporal lobe function, which cannot account for the opposing effects of the 2 lesions. These results are, however, compatible with a view that perirhinal cortex, and not the hippocampus, contains complex configural representations of visual stimuli critical to the solution of the transverse-patterning task.

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Previous studies have shown that perirhinal cortex lesions in monkeys impair visual discriminations with a high degree of "feature ambiguity," a property of visual discriminations that can emerge when features are a part of both rewarded and unrewarded stimuli. The effects of damage to the hippocampus on these perirhinal-dependent feature-ambiguous tasks are, however, unknown. Prominent theories of medial temporal lobe function predict similar effects of perirhinal cortex and hippocampal lesions on cognitive tasks. In contrast, our hypothesis is that perirhinal cortex, and not the hippocampus, is important for nonspatial complex feature-ambiguous discriminations. We sought to distinguish between these competing theories in a straightforward way, by testing rhesus monkeys with hippocampal lesions on the same feature-ambiguous tasks shown previously to depend on perirhinal cortex. It was found that hippocampal lesions had no effects on any of these tasks. The findings support the perceptual-mnemonic/feature conjunction model of perirhinal cortex function, and provide further evidence for heterogeneity of function within the putative medial temporal lobe memory system.

ABSTRACT:We describe a method for making selective lesions of the hippocampus in macaque monkeys, using a magnetic resonance imaging (MRI)-guided stereotaxic approach in which the excitotoxin N-methyl-Daspartic acid (NMDA) is injected at intervals along a single needle track that extends longitudinally through the rostrocaudal extent of the hippocampus. Procedures were conducted on six rhesus monkeys (Macaca mulatta) and were assessed with either in vivo MRI (n ‫؍‬ 3) or postmortem microscopic examination of the tissue after standard histological processing of the brains (n ‫؍‬ 3). Based on our extensive experience with the standard stereotaxic procedure in which ibotenic acid (IBO) is injected via the dorsal approach, we report that the new method provides a viable and potentially advantageous alternative to the standard procedure.