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.

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. / Arts, Faculty of / Psychology, Department of / Graduate

Food-caching birds like black-capped chickadees offer unique advantages for studying neural processes underlying episodic memory. Chickadees exhibit prodigious memories—they can cache thousands of food items throughout their environment and use memory to navigate back to these hidden food stores. Additionally, their hippocampal circuit is simplified relative to that of mammals, containing far fewer inputs and outputs. However, little work had been done to understand the neural processes underlying these animal’s memory abilities. This thesis details several projects that aimed to better establish food-caching birds as an animal model of memory for systems neuroscience. In Chapter 2, we described the creation of behavioral tasks to utilize the chickadees’ natural memory behavior. Here, we monitored chickadees’ behavior while they cached food into a grid of sites covered by rubber flaps. We then applied probabilistic modeling to examine how different strategies guided birds’ choices during caching and retrieval. Chickadees used memories of the contents of individual cache sites in a context-dependent manner, avoiding sites that contained food during caching and returning to those same sites during retrieval. These results demonstrate memory flexibility in an animal in a tractable spatial paradigm. In Chapter 3, we asked whether the bird brain had a region that was similar to the entorhinal cortex. We found that the dorsal lateral hippocampal formation (DL/CDL), one of the main inputs to the chickadee hippocampus, sharded marked anatomical and physiological similarities to the mammalian entorhinal cortex. We first used retrograde and anterograde tracing to examine the connectivity between DL/CDL and the hippocampus, as well as DL and the rest of the pallium. We found that the topographic patterns of DL/CDL input were similar to those of the mammalian entorhinal cortex. We next examined the physiology of DL, using 1-photon calcium imaging to monitor neural activity while birds performed a random foraging task. Like the entorhinal cortex, DL contained multi-field ‘grid-like’ spatial neurons, as well as border cells, head direction cells and speed-tuned cells. Collectively, these results establish DL/CDL as an entorhinal cortex analog. In Chapter 4, we expanded the anatomical analysis to examine all of the inputs to the hippocampal formation. We varied our injections of retrograde tracers along the hippocampal long and transverse axes to examine if, like in mammals, there were topographic input patterns along these major axes. We found many patterns in input that were highly reminiscent of mammalian connectivity: like in rodents, visual pallial input preferentially innervated the septal portion of the hippocampus, while amygdala input preferentially targeted the temporal portion. These results further solidify the homology between the mammalian and avian hippocampal formations. Collectively, through these sets of experiments, we have laid the groundwork for studying the black-capped chickadee in a modern neuroscience context.