Trial-unique, delayed nonmatching-to-location (TUNL): a novel, highly hippocampus-dependent automated touchscreen test of location memory and pattern separation.

The hippocampus is known to be important for learning and memory, and is implicated in many neurodegenerative diseases. Accordingly many animal models of learning and memory focus on hippocampus-dependent tests of location learning and memory. These tests often use dry mazes or water mazes; however automated testing in operant chambers confers many advantages over such methods. Some automated tests of location memory, such as delayed nonmatching-to-position (DNMTP) have, however, fallen out of favor following the discovery that such tasks can be solved using mediating behaviors that can bridge the delay and reduce the requirement for memory per se. Furthermore some researchers report that DNMTP performance may not always require the hippocampus. Thus, in an attempt to develop a highly hippocampus-dependent automated test of location memory that elicits fewer mediating behaviors, we have developed a trial-unique nonmatching-to-location (TUNL) task, carried out in a computer-automated touchscreen testing apparatus. To test the efficacy of this assay, rats with lesions to the hippocampus, or a sham lesion control group, were tested under a variety of conditions. Both groups were able to perform well at a delay of 1s, but the lesion group was highly impaired when tested at a 6s delay. Moreover, animals with lesions of the hippocampus showed a greater impairment when the distance between the locations was reduced. This result indicates that TUNL can be used to investigate both memory across a delay, and spatial pattern separation (the ability to disambiguate similar spatial locations). Performance-enhancing mediating behaviors during the task were found to be minimal. Thus, the TUNL task has the potential to serve as a powerful tool for the study of the neurobiology of learning and memory.