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Issued also as Thesis (Ph. D.)--University of Michigan. / An experiment in maze learning, developed with fifteen albino rats. Bibliography: p. 64-65.

Issued also as thesis (PH. D.) University of Michigan. / An experiment in maze learning, developed with fifteen albino rats. "References": p. 64-65.

The purpose of this experiment was to compare traditional frontal pole lesions (FP) with lesions of the median dorsal nucleus projection (MDNP) described by Leonard. First, a comparison was made on the retention of spatial discrimination learning and the new learning of spatial discrimination reversals between these two groups of frontally lesioned rats. It was hypothesized that the most severe deficits in spatial reversal learning would be shown in rats receiving MDNP lesions since this area of the rat cortex appears to be homologous to the frontal cortex of higher species according to Leonard’s results. Second, activity was measured on two post-operative occasions, before and after the reversal learning tasks, in both a familiar and an unfamiliar environment.

The present thesis examined extinction of conditioned fear in the developing rat. In the adult rat, the hippocampus is thought to be important for the context-specificity of extinction. Because the hippocampus is a late-maturing structure, it was hypothesised that context-modulation of extinction may be different across development. The first series of experiments investigated reinstatement of extinguished fear in the developing rat (Chapter 2). The results showed that P24 rats exhibited context-specific reinstatement. On the other hand, P17 rats did not exhibit reinstatement of extinguished fear following a US reminder treatment. The failure to see reinstatement in P17 rats was not due to the reminder treatment being ineffective in these rats because the same treatment alleviated spontaneous forgetting in rat this age. The second series of experiments then examined the renewal effect and GABAergic involvement in extinction in P24 and P17 rats (Chapter 3). It was observed that P24 rats displayed renewal whereas P17 rats did not. Also, pre-test injection of FG7142 recovered extinguished fear in P24 rats but not in P17 rats, even across a range of doses. This failure to see any FG7142 effect on extinction in P17 rats was not due to the lack of responsiveness to this drug in these rats because FG7142 was found to be effective in alleviating spontaneous forgetting in rats this age. The third series of experiments then examined the effect of temporary inactivation of the amygdala on extinction and re-extinction in the developing rat (Chapter 4). It was observed that extinction retention is impaired in both P24 and P17 rats if the amygdala is inactivated during extinction training. Interestingly, when a CS that had been previously extinguished and then re-trained was re-extinguished, re-extinction was amygdala-independent if initial extinction occurred at 24 days of age but amygdala-dependent if initial extinction occurred at 17 days of age. That is, amygdala involvement in re-extinction was dissociated across development. Taken together, these experiments provide strong evidence for fundamental differences in mechanisms underlying fear extinction across development. The implications of the findings were discussed in light of the theoretical and neural models of extinction.

The present thesis examined extinction of conditioned fear in the developing rat. In the adult rat, the hippocampus is thought to be important for the context-specificity of extinction. Because the hippocampus is a late-maturing structure, it was hypothesised that context-modulation of extinction may be different across development. The first series of experiments investigated reinstatement of extinguished fear in the developing rat (Chapter 2). The results showed that P24 rats exhibited context-specific reinstatement. On the other hand, P17 rats did not exhibit reinstatement of extinguished fear following a US reminder treatment. The failure to see reinstatement in P17 rats was not due to the reminder treatment being ineffective in these rats because the same treatment alleviated spontaneous forgetting in rat this age. The second series of experiments then examined the renewal effect and GABAergic involvement in extinction in P24 and P17 rats (Chapter 3). It was observed that P24 rats displayed renewal whereas P17 rats did not. Also, pre-test injection of FG7142 recovered extinguished fear in P24 rats but not in P17 rats, even across a range of doses. This failure to see any FG7142 effect on extinction in P17 rats was not due to the lack of responsiveness to this drug in these rats because FG7142 was found to be effective in alleviating spontaneous forgetting in rats this age. The third series of experiments then examined the effect of temporary inactivation of the amygdala on extinction and re-extinction in the developing rat (Chapter 4). It was observed that extinction retention is impaired in both P24 and P17 rats if the amygdala is inactivated during extinction training. Interestingly, when a CS that had been previously extinguished and then re-trained was re-extinguished, re-extinction was amygdala-independent if initial extinction occurred at 24 days of age but amygdala-dependent if initial extinction occurred at 17 days of age. That is, amygdala involvement in re-extinction was dissociated across development. Taken together, these experiments provide strong evidence for fundamental differences in mechanisms underlying fear extinction across development. The implications of the findings were discussed in light of the theoretical and neural models of extinction.

There is a prevalent assumption in the recognition memory literature that the terms “novelty” and “familiarity” are words ascribed to differing extremities of a single memory strength continuum. The aim of the current thesis was to integrate experimental methodologies across human and rodents to further investigate novelty processing at both a cognitive and neural level, and assess whether it is dissociable from familiarity processing. This dissociation was questioned at a cognitive level in human participants in Experiments 1 to 3 and at a neural level in rats in Experiment 4 and 5. Participants were found to differentially assess novelty and familiarity when making confidence judgements about the mnemonic status of an item (Experiment 1). Additionally, novelty and familiarity processing for questioned items were found to be dissimilarly affected by the presence of a concurrent item of varying mnemonic statuses (Experiment 2 and 3). The presence of a concurrent familiar item did not impact novelty processing in the perirhinal cortex (Experiment 4 and 5), yet disrupted the neural networks established to be differentially engaged by novelty and familiarity (Experiment 5). These findings challenge the assumption that the terms “novelty” and “familiarity” relate to a single recognition memory process. Finally, to allow integration of the findings from the human and rodent experiments, the relationship between measures or recognition memory obtained from spontaneous object recognition (SOR) task in rats and recognition memory measures estimated from signal-detection based models of recognition memory in humans was investigated (Experiment 6 and 7). This revealed that novelty preference in the SOR was positively correlated to measures of recognition memory sensitivity, but not bias. Thus, this thesis argues for the future inclusion of a novelty as a dissociable process from familiarity in our understanding of recognition memory, and for the integrations of experimental methodologies used to test recognition memory across species.

Indiana University-Purdue University Indianapolis (IUPUI) / Assessments of delay discounting in rodent lines bidirectionally selected for home cage intake and preference of alcohol have had mixed findings. The current study sought to examine if delay discounting related differentially to alcohol seeking versus and alcohol drinking, two processes underlying alcohol intake and preference. Three strains of rats were utilized to answer this question Long Evans (LE), high alcohol drinking rats (HAD2), and alcohol preferring P rats. All strains were compared in an adjusting amount delay discounting task. Operant self-administration of alcohol was then assessed in the sipper tube model, and finally home cage drinking was assessed in a 24 hour 2 bottle choice paradigm. In the delay discounting it was found that the P rats were steeper discounters than both the LE and HAD2. In the sipper tube model, P rats displayed higher levels of seeking than both the HAD2s and the LE, but both the P rats and the HAD2s had higher intakes than the LE. During 24 hour home cage access, the P rats and the HAD2s had higher intake and preference for alcohol than the LE, but were not different from each other. These results show that increased discounting of delayed rewards tracks with appetitive processes versus consummatory factors and home cage intake of alcohol. This builds on prior findings using selected line pairs by providing an explanation for discordant results, and supports the hypotheses that increased delay discounting is an intermediate phenotype that predisposes individuals to alcohol use disorders.