Disconnection of the hippocampal-perirhinal cortical circuits severely disrupts object-place paired associative memory.

The hippocampus and the perirhinal cortex (PR) are reciprocally connected both directly and indirectly via the entorhinal cortex. Although it has been hypothesized that the two regions should have intimate functional interactions with each other on the basis of the anatomical connectivity, many lesion studies have demonstrated functional dissociations instead between the hippocampus and PR. To show a tight functional relationship between the two regions, we used reversible inactivation techniques targeting both the hippocampus and PR within subjects, combined with a biconditional memory task in which the rat must consider information about objects and their locations. Specifically, rats were implanted with two sets of bilateral cannulas into the hippocampus and PR, and were tested in an object-place paired-associate task in a radial maze. While alternating between two arms, the rats were required to choose one of the objects exclusively associated with a given arm for food. Bilateral muscimol (MUS) injections into either the hippocampus or PR equally produced chance level performance. When a functional disconnection procedure was used to disrupt the interaction between the hippocampus and PR, contralateral MUS injections into the hippocampus and PR resulted in severe impairment in performance. However, inactivating the hippocampus and PR ipsilaterally did not affect the performance. In a simple object discrimination task, the same functional disconnection protocol with MUS did not affect the performance. The results powerfully demonstrate that the hippocampus, the PR, and their functional interactions are all indispensable when objects and their spatial locations must be processed at the same time.