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The development of a rat model of brain-damage-produced amnesia

University of British Columbia

The nonrecurring-items delayed nonmatching-to-sample (DNMS) task is an integral part of contemporary monkey models of brain-damage-produced amnesia. This thesis began the development of a comparable rat model of brain-damage-produced amnesia. First, a DNMS task for rats was designed by adapting key features of the monkey task. Then, the rat DNMS task was studied in three experiments; each assessed the comparability of the rat DNMS task to the monkey DNMS task. Experiment 1 determined the rate at which the rat DNMS task is learned and the asymptotic level at which it is performed, Experiment 2 assessed the memory abilities that it taps, and Experiment 3 investigated the brain structures that are involved i n its performance. In Experiment 1, rats were trained on the DNMS task and their performance was assessed at retention delays of 4, 15, 60, 120, and 600 s. All of the rats learned the DNMS task, and their performance was comparable to that commonly reported for monkeys in terms of both the rate at which they acquired the nonmatching rule at a brief retention delay and their asymptotic accuracy at delays of up to 120 s. These results establish that rats can perform a DNMS task that closely resembles the monkey DNMS task and that they can approximate the level of performance that is achieved by monkeys. Experiment 2 examined the effects of distraction during the retention delay on the DNMS performance of rats. Rats were tested at retention delays of 60 s. On half of the trials, the rats performed a distraction task during the retention delay; on the other half, they did not. Consistent with findings from monkeys and humans, distraction during the retention delay disrupted the DNMS performance of rats. This suggests that similar memory abilities are involved in the DNMS performance of rats, monkeys, and humans. Experiment 3 investigated the effects of separate and combined bilateral lesions of the hippocampus and the amygdala on DNMS performance in pretrained rats. Rats were tested both before and after surgery at retention delays of 4, 15, 60, 120, and 600 s. Each experimental rat received bilateral lesions of the hippocampus, amygdala, or both. There were no significant differences among the three experimental groups, and the rats in each of the three experimental groups were significantly impaired, in comparison to no-surgery control rats, only at the 600-s delay. In contrast, rats that had sustained inadvertent entorhinal and perirhinal cortex damage during surgery displayed profound D N M S deficits. These results parallel the results of recent studies of the neural basis of DNMS in monkeys. They suggest that, in contrast to one previously popular view, neither the hippocampus nor the amygdala play a critical role in the DNMS of pretrained animals and that the entorhinal and perirhinal cortex are critically involved. On the basis of these findings, it appears that the rat DNMS task may prove to be a useful component of rat models of brain-damage-produced amnesia. This conclusion is supported by the preliminary results of several experiments that are currently employing the task.

Thesis/Dissertation

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2008-12-23

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http://hdl.handle.net/2429/3293

Psychology

University of British Columbia

UBCV

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