This thesis assessed the impacts of acute and chronic phase-shifting on learning and memory in male and female rats. Previous research has revealed impaired retention immediately following circadian disruption and on the acquisition of new associations. However, whether behaviour resumes normality following circadian re-entrainment is unresolved. Following circadian re-entrainment, retention of pre-phase-shift acquired associations on Morris water task (MWT) and a visual discrimination task designed on the 8-arm radial maze were tested. Subsequently, an extradimensional set shift (EDS) using the 8-arm radial maze was performed. Acute circadian disruption negatively impacted retention in males and females, but only male rats without running wheels exhibited impairment following chronic phase-shifting on MWT performance. Retention on the visual discrimination task was impaired following chronic, but not acute, circadian disruption. Chronic, but not acute, phase-shifting negatively impacted performance on the EDS. Generally, phase-shifting produced differential negative impacts on cognitive function in rats. / xiv, 181 leaves : ill. (some col.) ; 29 cm

Conventional cylinder test measures have limited sensitivity in determining hemiparkinson rat forelimb use asymmetry and approximating substantia nigra (SN) dopaminergic neuron loss. This thesis investigates which cylinder test measures of hemiparkinson rat forelimb use asymmetry best predict methamphetamine-induced rotation and extent of dopaminergic neuron loss. Long-Evans rats were cylinder-tested after unilateral 1-methyl-4-phenylpyridinium (MPP+)-induced SN dopamine depletion. Time and count of numerous forepaw wall contact patterns were documented for MPP+ hemiparkinson rats and sham-operated controls using frame-by-frame video analysis, then regressed against methamphetamine-induced rotation and tyrosine hydroxylase-positive neuron depletion. Severely dopamine-asymmetric rats initiated movements slower and less often with the contralateral-to-lesion forepaw, indicating that the cylinder test may be used to assess Parkinson Disease motor impairments of bradykinesia and akinesia. Several new time and count asymmetry measures may improve cylinder test sensitivity to hemiparkinson-specific forelimb use asymmetries. / xi, 103 leaves : ill. ; 29 cm.

This thesis investigates the role of the hippocampus in object memory. Currently, the role of the hippocampus in object recognition is unclear, with some studies demonstrating a delay-dependent impairment after hippocampal damage, others showing no impairment. The present thesis used the novel object recognition task and its variants to investigate various types of object memory in hippocampal lesion rats. In the first study, impairments were observed in discriminating object order and associating objects with contexts, while no impairment was observed in novel object recognition. In the second study, it was found that encountering another object shortly prior to or after encountering a target object impairs the recognition of the target object. In a control procedure, encountering a novel context either shortly before or after encountering the target object did not impair object recognition. In sum, in the absence of the hippocampus, object memory becomes vulnerable to interference, rendering rats unable to discern memories of multiple objects. The present thesis concludes that the hippocampus discriminates multiple objects via pattern separation. A stimulus-response model relating the role of the hippocampus to object memory is proposed. / vii, 150 leaves : ill. ; 29 cm. --

The current work explores the behavioural and anatomical consequences of unilateral neonatal bulbectomy (OBX) in male and female rats at postnatal day 1 (PI) and P10. In adulthood the animals underwent a battery of motor and cognitive tests, and diffuse effects of early brain injury on the development of behavior were found. Disturbing olfactory sense input during development affected motor output. Rats normally display an equal distribution of right or left paw preference. In this study, both OBX sexes showed a shifted paw preference to the ipsilesional side, and forelimb deficits were found in a skilled reaching task. Lesion animals also showed enhanced performance on a visually driven spatial cognitive test. Cross-modal compensatory changes may be responsible. Morphological changes within the cerebral cortex are described, including bulbar changes, enlarged but fewer glomeruli, smaller accessory olfactory bulb, decreased downstream connectivity, and a rostral shift of the forebrain toward the olfactory bulb. Changes to the lateral cortex were found in both intact and lesion hemispheres, along with dendritic changes in the forelimb reaching area. Cellular regeneration within the lesion bulb was indicated. Changed shape and relative size increases compared to the intact bulb were found. BrdU labeling showed increased mitotic activity in P10 lesion animals. These findings demonstrate that the impact of olfactory injury during early development goes well beyond odor perception and discrimination, and that olfactory inputs during development significantly contribute to the development of the neocortex. / xix, 195 leaves : ill. (some col.) ; 29 cm.

Adult neurogenesis is a fundamental feature of mammalian nervous systems. Curiously, neurogenesis in the dentate gyrus is typically regarded as homogenous. This thesis challenges that view, and reports the discovery and characterization of a novel region of the dentate gyrus that consistently lacks basal neurogenesis. We demonstrate that this area, referred to as the neurogenically quiescent zone, represents approximately 1.5% of the total volume of the dentate gyrus, and that its location is invariant among animals. This region contains several critical cell types and molecular factors that are known to be critical to the neurogenic niche, including stem cells. We also present data that attempt to conceptualize the existence of this region in the context of early agerelated declines in neurogenesis. Finally, we demonstrate that, under some behavioural conditions, neurogenesis can be induced in this region, suggesting that, under basal conditions, it may simply lack the presence of pro-neurogenic factors. / xvi, 125 leaves : ill. ; 29 cm. --

The hippocampus and non-hippocampal long-term memory systems each have the capacity to learn and express contextual fear memory. How these systems interact during learning and remembering revolves around hippocampal mediated interference, where the hippocampus dominates for both the acquisition and expression of long-term memory. Hippocampal interference during learning can be overcome by modifying learning parameters such that learning is distributed across multiple independent sessions. The standard view of the role of the hippocampus in long-term memory retrieval is that it is temporally limited, where recently acquired memory is dependent on hippocampal function though as a memory ages, dependency is transferred to other memory systems by a process called systems consolidation. Distributed training demonstrates that learning parameters create a memory that is resistant to hippocampal damage. We find little evidence to support temporally based systems consolidation, and present data that supports the view that if the hippocampus is initially involved in learning a memory, it will always be necessary for accurate retrieval of that memory. A critical assessment of the rat literature revealed that initial memory strength, and/or lesion techniques might be responsible for the few studies that report temporally graded retrograde amnesia using contextual fear conditioning. Our experiments designed to directly test these possibilities resulted in flat gradients, providing further evidence that the hippocampus plays a permanent role in long-term memory retrieval. We propose and assess alternatives to the standard model and conclude that a dual store model is most parsimonious within the presented experiments and related literature. Interactions of the hippocampus and non-hippocampal systems take place at the time of learning and remembering, and are persistent over time. / xvi, 161 leaves : ill. (some col.) ; 29 cm

This thesis examines both behavioral and anatomical effects of prenatal exposure of Valproic Acid (VPA) on Long Evans rats. Tactile stimulation (TS) is then used to investigate its’ effect on remediating any abnormalities VPA may produce. Several behavioral tests were done to assess the behavioral effects of VPA and TS. It was found that VPA had an effect of many of the tasks, whereas, TS had almost none with the exception of an effect on females in the elevated plus maze. However, anatomical data showed that TS had a profound effect on neuronal branch order, cell complexity, and spine density in pyramidal neurons in the medial prefrontal cortex, the orbitofrontal cortex and the amygdala. Where VPA decreased the above in all of these areas, TS increased neuronal complexity in the aforementioned structures. This study demonstrates that prenatal exposure to VPA is a viable model of autism in rats and that TS has significant anatomical effects in these animals as well as in control animals / xi, 98 leaves; 29 cm

NMDA receptor antagonists such as Ketamine and PCP are potent psychoactive drugs used recreationally. This class of drug induces a number of phenomena in humans similar to those associated with schizophrenia including reduced selective attention, altered working memory, thought disorders and hallucinations. These psychotomimetic drugs have thus been used as a longstanding model to study this disease in animals. Importantly, such animal models allow for recording of brain activity using invasive techniques that are inappropriate in humans. Previous electrophysiological studies have shown that MK-801, a potent non-competitive NMDA receptor antagonist, increases gamma-frequency oscillations and produces a state of disinhibition in the prefrontal cortex of rats wherein the activity of putative excitatory pyramidal neurons increases while the activity of putative inhibitory interneurons decreases. These features are relevant to schizophrenia because molecular evidence suggests dysfunction of inhibitory cortical interneurons, while electroencephalographic recordings show altered gamma-frequency oscillations in this disease. It has been hypothesized that the disinhibited cortical state produces “noisy” information processing, but this has not been directly observed in the interaction of neuronal firing in either humans or animal models. We therefore tested this hypothesis by examining the synchronization of neural activity in the NMDA receptor antagonist model of schizophrenia. We used high-density electrophysiological recordings in the medial prefrontal cortex of freely moving rats before and after systemic injection of MK-801. Analysis of these recordings revealed that drug administration: (i) increases gamma power in field potentials in a manner dissociated from increased locomotion; (ii) does not change the gamma power in multi-unit activity; (iii) decreases spike synchronization among putative pyramidal neurons in the gamma range (30ms), and despite of this it (iv) does not change the synchronization between gamma-range field potentials or between sum-of-spikes and field potentials. These effects in synchronization may be revealing of potent cognitive effects associated with NMDA receptor antagonism, and may reflect impaired communication processing hypothesized to occur in schizophrenia. / xi, 42 leaves : ill. ; 29 cm

No description available.

No description available.