Over the past five decades spatial behavior has been a subject of research interest in psychology and neuroscience, in part based on philosophical theories of mental spatial representations. In order to continue uncovering the facts regarding spatial behavior, the focus of this thesis was on the contribution of entry point and visual inputs to the organization of exploratory locomotion and spatial representation in the rat. Despite the contribution of the hippocampus to spatial abilities, the exploratory locomotion is still visually organized in rats with damage to the hippocampus. On the other hand, recent studies have demonstrated a contribution of visual areas to the spatial ability of the rat. Nevertheless, the contribution of visual cortex to the organization of exploratory locomotion has not been studied in an open field. The experiments in this thesis were designed to characterize the organization of exploratory locomotion to the point of entry and/or visual cues. Rats were started from the edge or center of an open table near or on which a salient object could be placed. The main findings were that rats organized their exploratory locomotion to their point of entry and modified their behavior as they encountered objects. Also, rats with damage to visual cortex displayed an extra-attachment to the visual objects and in contrast to controls did not expand their exploratory locomotion with time. The results are discussed with respect to the centrality of the entry point in the organization of exploratory locomotion and the neural network that control visual exploration in the rat. / xiii, 220 leaves : ill. ; 29 cm. --

The present thesis investigates the effects of lesions to several hypothesized learning and memory systems on the morphine conditioned cue preference on the radial maze. Lesions of the structures thought to be centered to learning systems: the lateral nucleus of amygdala, fornix/fimbria, anterior dorsal striatum and posterior dorsal striatum, were made, In Experiment One, each structure was lesioned separately. Only lesions of the lateral nucleus of amygdala blocked morphine CCP learning. In Experiment Two, rats with combined lesions of fornix/fimbria and dorsal striatum, the lateral nucleus of amygdala and fornix/fimbria, as well as the lateral nucleus of amygdala and dorsal striatum were all impaired on morphine CCP. All of the rats with combined lesions were impaired in this CCP learning. These findings suggest that the lateral nucleus of amygdala is necessary for the morphine CCP. Participation of dorsal striatum or fornix/fimbria is also required. Some hypotheses about the interactions among the structures are discussed.

The experiments reported in the present dissertation investigated the contribution of the mammillary region to several classes of learning and memory: spatial memory, nonspatial memory, and conditioned aversion learning. It was demonstrated that such lesions impair performance on tasks that require memory for spatial information but that the deficit depends on both the amount of damage within the region as well as the degree of difficulty of the task. A dissociation in the effect of such lesions on performance of comparable spatial and nonspatial memory tasks was shown. In contrast to the severe deficits observed on spatial memory tasks, the acquisition and retention of a complex nonspatial memory task was not impaired after extensive damage to the mammillary region. Such lesions also did not impair performance on two conditioned aversion tasks. These experiments suggest that the mammillary region may be selectively involved in spatial learning and memory. The relevance of these findings to Korsakoff's syndrome is discussed.

Attentional set-shifting tasks, consisting of multiple stages of discrimination learning, have been widely used in animals and humans to investigate behavioural flexibility. However, there are several learning criteria (e.g., 6-correct-choice-in-a-row, or 10-out- of-12-correct) by which a subject might be judged to have learned a discrimination. Furthermore, the currently frequentist approach does not provide a detailed analysis of individual performance. In this PhD study, a large set of archival data of rats performing a 7-stage intra-dimensional/extra-dimensional (ID/ED) attentional set- shifting task was analysed, using a novel Bayesian analytical approach, to estimate each rat's learning processes over its trials within the task. The analysis showed that the Bayesian learning criterion may be an appropriate alternative to the frequentist n- correct-in-a-row criterion for studying performance. The individual analysis of rats' behaviour using the Bayesian model also suggested that the rats responded according to a number of irrelevant spatial and perceptual information sources before the correct stimulus-reward association was established. The efficacy of the Bayesian analysis of individual subjects' behaviour and the appropriateness of the Bayesian learning criterion were also supported by the analysis of simulated data in which the behavioural choices in the task were generated by known rules. Additionally, the efficacy was also supported by analysis of human behaviour during an analogous human 7-stage attentional set-shifting task, where participants' detailed learning processes were collected based on their trial-by-trial oral report. Further, an extended Bayesian approach, which considers the effects of feedback (correct vs incorrect) after each response in the task, can even help infer whether individual human participants have formed an attentional set, which is crucial when applying the set-shifting task to an evaluation of cognitive flexibility. Overall, this study demonstrates that the Bayesian approach can yield additional information not available to the conventional frequentist approach. Future work could include refining the rat Bayesian model and the development of an adaptive trial design.

Schizophrenia is a neuropsychological disorder in which the neural systems which regulate attention allocation, primarily the dorsolateral prefrontal cortex, are dysfunctional, resulting in deficient gating of attention to irrelevant inputs from the environment. This sensory processing dysfunction hinders goal-directed behaviour to the extent that the subsequent cognitive deficits of schizophrenia prevent many chronic patients from leading normal lives. It is the onus of neuroscience to understand the nature of deficits induced by the disorder, thus providing target mechanisms for remediation of those deficits in patients. To accomplish this, manipulations in rats with relevance to schizophrenia are examined in assays with translation to human neurobiology and behaviour. In this thesis, three manipulations with relevance to schizophrenia, were examined for attentional regulation in the attentional set-shifting task, and similar assays, to determine how different forms of schizophrenia-related pathology influence attentional regulation and behavioural flexibility. The foremost findings of the experiments herein were that manipulations inducing schizophrenia-related neurobiology, resulted in impaired performance in extradimensional set-shifting and reversal learning. These deficits were found following: acute inhibition of the mPFC in adult rats, in adult rats who had been exposed to a glutamate receptor antagonist during the neonatal period of development, and/or in adult rats who had gestational disruption of neuron proliferation. Across all three manipulations, a clear behavioural pattern of deficient sensory gating, evidenced by responding to irrelevant stimuli during the set-shifting task was found. These findings suggest that at the core of the cognitive deficits in schizophrenia is the ‘loosening of associations' such that patients suffer the inability to regulate attention, and limit sensory processing to relevant information. The subsequent aberrant learning about irrelevant information then impairs performance during goal-directed behaviours.

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Since hunger drive is often used as a motivating factor in animal learning experimentation, it was decided to determine the effects of marihuana extract distillate on the eating behavior of rats. Carlini and Kramer (1965) found marihuana extract injections to have a faciliatory effect upon maze performance. They suggested that facilitation could have resulted from and increase in hunger drive. However, if the dosage level is high, this effect may last for a short time and be followed by a disinterest in food. Scheckel et al. (1968) report that some monkeys, at very high dosage levels of tetrahydrocannabinol starved to death in post-drug depressions. Human studies indicate some increased hunger or "taste enhancement" (Grinspoon, 1968; Hollister, et al., 1968; Ames, 1958). Ss were 20 male and 20 female adult Sprague-Dawley albino rats, maintained in home cages with ad-lib food and water. Each animal was assigned to one of five groups so that each group contained four males and four females. Each group received one dosage level of the drug throughout the entire experiment. Three dosage levels and two controls were used. Food deprivation levels of ad-lib, 12, 24, and 48 hours were assigned according to a balanced Latin square design. The drug, marihuana extract distillate, was administered through an intraesophogeal tube and hypodermic syringe. The study was divided into two parts, each of four weeks' duration. In the first, after administration of the frug, the animals immediately were placed into a cage with a known amount of food present. The food was weighed after three and 24 hours to determine the amount of food eaten. The second experiment in the study repeats all proc3edures except animals were not given food until 1/2-hour after the drug was administered. Results show an inverse relationship between dosage level of marihuana extract distillate and amount of food eaten. Effects of dosage level, hours of deprivation, sex, latency of food preparation, and the possibility of tolerance or increased sensitivity to the drug are discussed.

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