Dentate gyrus is necessary for disambiguating similar object-place representations.

Objects are often remembered with their locations, which is an important aspect of event memory. Despite the well-known involvement of the hippocampus in event memory, detailed intrahippocampal mechanisms are poorly understood. In particular, no experimental evidence has been provided in support of the role of the dentate gyrus (DG) in disambiguating such events, even though computational models suggest otherwise. In the current study, rats encountered multiple objects in different locations and were required to discriminate the object-place paired associates for reward. Specifically, two different objects appeared in one of two locations (arms in a radial maze) that were relatively close to each other. Different objects were rewarded depending on the arm in which the objects appeared. The rats with colchicine-based, dorsal DG (dDG) lesions showed severe and sustained impairment in disambiguating the objects compared with controls (Experiment 1). The dDG-lesioned rats were normal, however, in discriminating four different objects presented (Experiment 2) in the same locations as in Experiment 1. Finally, when the two different objects used in Experiment 1 were presented at two remote locations (Experiment 3) involving less overlap between arm-associated contextual cues, the dDG-lesioned animals showed initial deficits in discriminating the objects, but gradually relearned the task, in contrast to the sustained deficits observed in Experiment 1. These results collectively suggest that the DG is necessary when the similarity is maximal between object-place paired associates due to overlapping object and/or spatial information, whereas its role becomes minimal as the overlap in either object or spatial information decreases.

The roles of the medial prefrontal cortex and hippocampus in a spatial paired-association task.

Although the roles of both the hippocampus and the medial prefrontal cortex (mPFC) have been suggested in a spatial paired-associate memory task, both areas were investigated separately in prior studies. The current study investigated the relative contributions of the hippocampus and mPFC to spatial paired-associate learning within a single behavioral paradigm. In a novel behavioral task, a pair of different objects appeared repeatedly across trials, but in different arms in a radial maze, and different rules were associated with those arms for reward. Specifically, in an "object-in-place" arm, the rat was required to choose a particular object associated with the arm. In a "location-in-place" arm, the animal was required to choose a certain within-arm location (ignoring the object occupying the location). Compared to normal animals, rats with ibotenic acid-based lesions in the hippocampus showed an irrecoverable impairment in performance in both object-in-place and location-in-place arms. When the mPFC was inactivated by muscimol (GABA(A) receptor agonist) in the normal animals with intact hippocampi, they showed the same severe impairment as seen in the hippocampal lesioned rats only in object-in-place arms. The results confirm that the hippocampus is necessary for a biconditional paired-associate task when space is a critical component. The mPFC, however, is more selectively involved in the object-place paired-associate task than in the location-place paired-associate task. The current task powerfully demonstrates an experimental situation in which both the hippocampus and mPFC are required and may serve as a useful paradigm for investigating the neural mechanisms of object-place association.