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. --

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

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This series of experiments used the multiple learning and memory systems hypothesis of the mammalian nervous system to investigate the possibility that the amygdala, dorsal striatum, and hippocampal systems might, in certain situations, interact to produce behavior in the normal animal. Using variations of the conditioned-cue preference (CCP) task, evidence is presented showing that context-specific information acquired by the hippocampus interferes with acquisition of amygdala-based stimulus-reward learning. It was also demonstrated that there are amygdala-, dorsal striatum-, and hippocampus-based forms of place learning and that cue ambiguity and movement are important factors determining which of these learning and memory systems gain behavioral control in place learning situations. These findings provide evidence for interactions among learning and memory systems and implicate the amygdala and dorsal striatum in some types of non-hippocampal based place learning using distal cues.

This study investigated the neural correlates of memory for human nonlinguistic emotional vocalizations as a function of individual differences in trait anxiety and depression. 20 healthy subjects (female; aged 18-30) free from neurological impairments or psychiatric illness underwent MRI scanning to obtain T1 structural images of their brain, and participated in a subsequent behavioral memory task outside the scanner. Volumetry of the hippocampus and amygdala was performed using a validated protocol. We found emotional vocalizations were better remembered than neutral ones, with performance for negative better than positive. Memory performance for emotional items was associated with hippocampal volume, with no association between memory and I amygdala volume detected. Differences in anxiety or depression had no influence on memory or volume. These results lay the groundwork for future functional neuroimaging work to investigate the neural correlates of memory, personality, and brain structure volume in healthy and clinical populations.

<p> <p>&nbsp / </p> </p> <p align="left">This study utilized large-scale gene expression data to define the regulatory networks of genes expressing in the hippocampus to which multiple disease pathologies may be associated. Specific aims were: ident i fy key regulatory transcription factors (TFs) responsible for observed gene expression patterns, reconstruct transcription regulatory networks, and prioritize likely TFs responsible for anatomically restricted gene expression. Most of the analysis was restricted to the CA3 sub-region of Ammon&rsquo / s horn within the hippocampus. We identified 155 core genes expressing throughout the CA3 sub-region and predicted corresponding TF binding site (TFBS) distributions. Our analysis shows plausible transcription regulatory networks for twelve clusters of co-expressed genes. We demonstrate the validity of the predictions by re-clustering genes based on TFBS distributions and found that genes tend to be correctly assigned to groups of previously identified co-expressing genes with sensitivity of 67.74% and positive predictive value of 100%. Taken together, this study represents one of the first to merge anatomical architecture, expression profiles and transcription regulatory potential on such a large scale in hippocampal sub-anatomy.</p>

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A word-generation experiment explored the relative contributions of the left temporal neocortex and the left hippocampal region to verbal recall. Patients with large hippocampal excisions (LTH) were impaired in immediate recall of synonyms, whereas those with small hippocampal excisions (LTh) were not. Both groups were impaired in immediate recall of rhymes, and in delayed recall of both synonyms and rhymes. A nonverbal associative-learning task, where the stimulus-items came from a visual continuum, also resulted in a deficit for the LTH (but not the LTh) group. Patients with right temporal lobectomy performed both tasks normally. On an absolute-judgement task involving the accurate numbering of a set of six individually-presented rectangles, only the groups of patients with large hippocampal excisions were impaired, regardless of side of lesion. These findings support the view that the temporal neocortex is important for gaining access to information in semantic memory, whereas the hippocampal region is essential for the temporary storage of new information beyond the span of immediate memory.