Hippocampus is required for paired associate memory with neither delay nor trial uniqueness

Abstract

Cued retrieval of memory is typically examined with delay when testing hippocampal functions, as in delayed matching-to-sample tasks. Equally emphasized in the literature, on the other hand, is the hippocampal involvement in making arbitrary associations. Paired associate memory tasks are widely used for examining this function. However, the two variables (i.e., delay and paired association) were often mixed in paired associate tasks, and this makes it difficult to localize the cognitive source of deficits with hippocampal perturbation. Specifically, a few studies have recently shown that rats can learn arbitrary paired associations between certain locations and nonspatial items (e.g., object or flavor) and later can retrieve the paired location when cued by the item remotely. Such tasks involve both (1) delay between sampling the cue and retrieving the target location and (2) arbitrary association between the cueing object and its paired location. Here, we tested whether delay was necessary in a cued paired associate task by using a task in which no delay existed between object cueing and the choice of its paired associate. Moreover, fixed associative relationships between the cueing objects and their paired locations were repeatedly used, thus involving no trial-unique association. Nevertheless, inactivations of the dorsal hippocampus with muscimol severely disrupted retrieval of paired associates, whereas the same manipulations did not affect discriminating individual objects or locations. The results powerfully demonstrate that the hippocampus is inherently required for retrieving paired associations between objects and places, and that delay and trial uniqueness of the paired associates are not necessarily required. © 2012 Cold Spring Harbor Laboratory Press.