The protein synthesis inhibitors cycloheximide and anisomycin were administered during training in an attempt to block the consolidation of the memory for a morphine conditioned place preference. The systemic injection of 2.5mg/kg of cycloheximide post-training failed to block consolidation, though there was a trend towards an attenuated preference, however cycloheximide produced a conditioned place aversion if paired with one compartment. To examine the effect of more complete protein synthesis inhibition and reduce the aversive effects, the less toxic protein synthesis inhibitor anisomycin was infused into the lateral ventricles of the brain either pre-, post- or 3 hours following training. Post-training infusions of anisomycin blocked the formation of a conditioned place preference, while pre-training and 3 hours post-training infusions showed no significant effect over two conditioning pairings. It was concluded that drug conditioning in the place preference paradigm requires protein synthesis for memory consolidation as do other learning paradigms.

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Memory refers to the retention of learned information or experiences in the brain. It is known that interference of certain brain functions immediately after training or memory reactivation can cause memory loss (i.e. amnesia). The post-training process is called consolidation and the post reactivation process is called reconsolidation. However, it remains unclear as to: (1) whether appetitive, goal-directed memories undergo reconsolidation, (2) whether overtrained memories undergo reconsolidation, (3) what the nature of amnesia is (i.e. whether it represents storage or retrieval impairment), (4) how to test the nature of amnesia, and (5) whether the brain uses the same mechanism for a new learning and from a second learning. This thesis, composed of five manuscripts, aims to answer these questions. In the first manuscript, the model of incentive learning of appetitive outcomes in instrumental conditioning was used. Protein synthesis inhibitor (PSI) was infused into lateral and basal amygdala (LBA) after the new incentive learning and after the reactivation of the memory. The results show that appetitive memories in controlling goal-directed behaviors underwent consolidation and reconsolidation in the LBA. In the second manuscript, rats were overtrained with auditory fear conditioning and received intra-LBA PSI infusions after memory reactivation. The results show that only old, but not recent, overtrained auditory fear memories underwent reconsolidation. This suggests overtraining sets a boundary condition on memory reconsolidation. Further results showed dorsal hippocampus and intra-LBA NR2B-subunit containing N-methyl-D-aspartic acid receptors (NMDAr) were involved in this boundary condition. In the third manuscript, the unresolved debate about the nature of amnesia was reviewed from a historical perspective and the suggestions on reconciling this issue are proposed. In the fourth manuscript, a new approach was used to test the nature of amnesia in contextual fear conditioning. Because NMDAr blockade impairs a new learning but not a second learning, it is predicted that if a memory is not stored then the second learning should be impaired by NMDAr blockade. The results suggest amnesia of contextual fear memory caused by intra-dorsal hippocampus (dH) PSI infusion represents a storage impairment which gives a different result from extinction induced irretrievability. In the fifth manuscript , the aim is to identify the brain mechanism for the second learning as the previous manuscript suggests it is different from the first learning mechanism. The results show that the first, but not the second learning required voltage-dependent calcium channels and activation in dH. The second learning was impaired by intra-dH or ventral hippocampus (vH) inactivation only when the protein synthesis in the other portion of hippocampus was blocked after training. This suggests while the first learning by default requires dH, the second learning can be acquired through a functional dH or vH. In summary, this thesis extends memory research from consolidating a new learning to characterizing the reconsolidation of appetitive and overtrained memory to consolidating a second learning which will lead to a more complete description of memory process.

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The aim of these experiments was to investigate learning and memory extensively in two nonverbal domains (olfactory and visual), and to determine similarities and differences in the function of the neural substrates that subserve these modalities. Two complementary methodological approaches were taken: (1) examination of learning and retention in patients with resection from left (LR) or right (RR) temporal lobe, and (2) study of brain function via Positron Emission Tomography (PET) of healthy subjects during memory processing. / Two parallel recognition tests were developed (one olfactory, one visual) that examined memory at three stages: following a single exposure to test stimuli, after four exposures, and following a 24hr delay interval. In the olfactory patient study, LR and RR groups performed significantly worse than the healthy control subjects, with no difference between the patient groups; thus suggesting a lack of hemispheric superiority for this task. The PET study of healthy individuals supported the bilateral participation of piriform cortex during olfactory recognition. The results from these two studies, along with findings from animal work, suggest that the piriform cortices may play a role in odor memory processing, not simply in perception. / On the face memory task, LR and RR patients showed different results. Only RR patients were impaired, while LR patients did not perform differently from controls. This unique face learning paradigm was sensitive to right temporal lobe damage, and correctly classified patients by side of resection with a sensitivity rate of 82% and specificity rate of 79%, suggesting its possible utility as a clinical tool. PET face memory findings indicated greater participation of fusiform regions during long-term recognition, and greater right prefrontal activity during short-term recognition, when these conditions are directly compared to each other. / Finally, PET was used to study the same healthy subjects performing parallel odor and face working-memory tasks, focusing on regions previously shown to be important for working memory. Results revealed similar regions of activation in dorsolateral prefrontal cortex in the two modalities. This indicates an overlap in the brain regions that process olfactory and visual information when the same cognitive manipulations are being carried out online.

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 objective of this thesis was to test the idea that medial thalamic nuclei are part of a "memory circuit" in the brain. Rats received lesions of the anterior (ANT) or medial dorsal (MD) thalamic nuclei and were tested on two spatial tasks, a nonspatial configural task, and spontaneous and amphetamine-induced acitivity. The thalamic rats were impaired on the spatial and conifural tasks, ans some of the thalamic groups were slightly hyperactive after administration of amphertamine. The deficits were not large and could not be unequivocally attributed to the ANT or MD damage. The results question the role of the ANT or MD in the behaviors studied. It is suggested that the deficits obtained after thalamic damage may be nonspecific and it is concluded that the results do not support the notion that thalamic structures have a primary role in memory. / xi, 187 leaves : ill., plates ; 29 cm.