The Development of an Object-Recognition Task for Rats and the Evaluation of the Internal Validity of the Novel-Object-Preference Test

Object-recognition—the ability to discriminate the familiarity of previously presented stimuli—is assessed in laboratory rats using the delayed nonmatching-to-sample (DNMS) task and the novel-object-preference (NOP) test. The DNMS task provides a fairly precise measure of a rat’s object-recognition abilities, however, it suffers from certain drawbacks. In particular, rats require extensive training and it cannot be used to assess memory for objects following periods lasting longer than several minutes. For these reasons, most researchers have abandoned it in favour of the NOP test. The NOP test is easy to use, as it relies on measuring a rat’s natural tendency to spend more time investigating a novel object over a familiar one when both are presented in a familiar context. Some concerns have been raised, however, regarding the internal validity of the NOP test. Accordingly, the goal of the present thesis was to develop a new object-recognition task that addresses the known limitations of the existent tests. A secondary goal of the thesis was to evaluate rats’ performance on the new task to that on the NOP test as a means to validate the latter. The first experiment describes rats’ performance on the new task –the modified DNMS (mDNMS) task. Rats required significantly fewer trials to learn the nonmatching rule compared to conventional DNMS tasks, and their scores showed good test re-test reliability. The same rats’ exhibited significant novelty-preference scores on the NOP test, however their scores showed poor test re-test reliability and were not significantly correlated with mDNMS scores. The latter finding suggests that the two tasks may not tax similar underlying cognitive processes. In the experiment presented in Chapter 3, memory for objects was assessed following delays lasting 72 hr, 3 weeks, and ~45 weeks on both the mDNMS task and NOP test. Rats successfully discriminated between novel and sample objects on the mDNMS task following all three delays, however, the same rats failed to exhibit significant novelty preferences following all three delays on the NOP test. These findings reveal that the mDNMS task can be used to assess long-term memory for objects, and that a failure to exhibit a novelty preference may not necessarily reflect the status of object-recognition memory. Next, we assessed rats’ performance on the mDNMS task and NOP test following surgical lesions made to either the hippocampus (HPC) or perirhinal cortex (PRh)—two brain areas implicated in object-recognition memory. Neither HPC nor PRh lesions failed to disrupt performance on the mDNMS task, but rats with PRh lesions failed to display a novelty preference on the NOP test. The discrepancy in the PRh rats’ performance on both tasks further adds to concerns regarding the internal validity of the NOP test, such that a lack of novelty preference is not necessarily indicative of an object-recognition memory impairment. The final experiment focused on refining the mDNMS task to include an additional behavioural measure—latency to make a choice. We incorporated a Go/No-go procedure and found that latency to make a choice provided a more sensitive measure of object-recognition memory than choice-accuracy on the test. Collectively, these findings confirmed the utility of the mDNMS task as a means to gauge object-recognition memory in rats. The results also highlight the limitations of the NOP test, and raise concerns regarding the internal validity of it as a means to measure object-recognition abilities in rats.

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