Understanding the process of associative learning between environmental stimuli and cocaine is essential for the prevention of drug-use relapse and long-term treatment of cocaine dependence. Based on contemporary learning theories, empirical studies using natural rewards have shown that cognitive factors, such as uncertainty and prediction errors, play an important role in the process of reward associative learning. Uncertainty is the lack of an accurate predictor for reward while prediction error is defined as the discrepancy between expected and received reward. In this dissertation, we focused on the role of uncertainty and prediction error in cocaine-associative learning. Olfactory and visual cues during self-administration/conditioning sessions were used to induce cocainereward expectation and uncertainty in operant trained catheterized Sprague Dawley rats. The influence of cue-induced uncertainty and prediction error on nucleus accumbens dopamine (NAcc DA) following self-administration of cocaine and saline in these conditioned animals was then measured using in-vivo microdialysis. Results showed that cocaine-stimulated NAcc DA was enhanced in the presence of cues signaling cocaine reward uncertainty (Uncertainty) as compared to animals expecting to get cocaine (Certainty). Also omission of expected cocaine reward (Prediction Error) resulted in a significant depression of NAcc DA levels below baseline. Recently diazepam (a positive GABAA modulator) has been shown to disrupt cocaine-induced LTP and it has been suggested that this disruption can block the acquisition of drug-associated memories. We therefore hypothesized that diazepam-pretreatment during conditioning sessions would disrupt the learned responses to cocaine and saline in the presence of cue-induced uncertainty and prediction error. Our results show that diazepam pretreatment duringconditioning sessions, blocked the differential cocaine-stimulated NAcc DA response to cue-induced certainty and uncertainty. Moreover, on omission of expected cocaine reward (Prediction Error) there was no significant depression of NAcc DA below baseline. The findings of this dissertation thus highlight the importance of cognitive factors (uncertainty and prediction errors) in the process of cocaine-associative learning. They also provide a platform to further explore the influence of these factors on other neuroadaptations during cocaine-associative learning, which will help us develop effective behavioral and pharmacological therapies to prevent drug-use relapse.

Paired comparison models in loglinear form are generalised linear models and can be fitted using the IWLS algorithm. Unfortunately, the design matrices can become very large and thus a method is needed to reduce computational load (relating to both space and time). This paper discusses an algorithm for fitting loglinear paired comparison models in the presence of many nuisance parameters which is based on partition rules for symmetric matrices and takes advantage of the special structure of the design matrix in Poisson loglinear models. The algorithm is implemented as an R function. Some simple examples illustrate its use for fitting both paired comparison models and (multinomial) logit models. (author's abstract) / Series: Research Report Series / Department of Statistics and Mathematics

Our knowledge of how Arctic freshwater ecosystems will respond to continued climate change and variability is fundamentally limited by logistical difficulties of such remote research, resulting in relatively sparse long-term baseline data on these systems. This research applies a unique paired-watershed approach (i.e., two similar, adjacent lakes and catchments) to help address these limitations, which provided an opportunity to identify how broad-scale factors are filtered or modified by site-specific characteristics. My first main objective was to document the seasonal hydrochemical variability of runoff and influences on lake chemistry. Both lakes appear to be relatively insensitive to seasonal hydroclimatic variability, largely because periods of high discharge were also characterized by lower concentrations of dissolved and particulate matter, but also because of the relatively long lake water turnover time that suggests the effects of climatic and environmental changes would be felt later in these systems than in lakes and ponds with smaller lake volumes. My second objective was to investigate spatial and temporal trends in the lake diatom communities in order to refine subsequent paleoenvironmental reconstructions. A critical aspect of this objective was testing how faithfully the whole lake diatom community was represented in deep lake surface sediments where sediment cores are routinely collected. Most differences between the two lakes were largely accounted for with micro-environmental conditions associated with the specific sampling location. Also, both lakes exhibited a degree of disconnection between littoral benthic and profundal zones that manifested as an under-representation of the benthic community in deep lake surface sediments, with implications for paleoenvironmental interpretations. Finally, I present a multi-proxy record of environmental conditions in adjacent lakes spanning the period from pre-industrial times. Biogeochemical records reflected major changes in lake primary productivity and terrestrial organic matter accumulation beginning prior to 1950 in both lakes, pointing to profound environmental changes that culminated with the establishment of an appreciable diatom community in both lakes in the 1980s. Differences in the timing of changes between the two lakes point to differing threshold capacities to external forcings, and suggest that East Lake’s response to post-industrial climate change is advanced compared to West Lake. / Thesis (Ph.D, Geography) -- Queen's University, 2011-10-26 09:34:01.144

The number of non-parasitic (brook) lamprey species in the genus Lampetra is underestimated since isolated populations are generally considered one species due to their relatively conserved body form. The phylogeographic and phylogenetic structure was estimated among and within Lampetra species along the Pacific coast of North America (presumed to represent Lampetra richardsoni; L. pacifica – which is currently regarded as a junior synonym of L. richardsoni; L. ayresii; and L. hubbsi) using up to three mitochondrial and three nuclear genetic markers. These data show that L. richardsoni as currently recognized is polyphyletic when lampreys (some of which show up to 8 K2P% sequence divergence) from Siuslaw River and Fourmile Creek (Oregon) and Mark West, Paynes, and Kelsey creeks (California) are included; Lampetra pacifica is a valid species; the population from Kelsey Creek almost certainly represents a new species; and those from Siuslaw, Fourmile, and Mark West may also be distinct species.

The ubiquitin proteasome system (UPS) depends on three enzymes called E1, E2, and E3 to ubiquitinate proteins and several isopeptidases to de-ubiquitinate them. Ubiquitination serves as a post-translational modification that either tags proteins for degradation by the proteasome or serves to modulate their function. This dynamic system plays a role in synaptic plasticity and dysfunction of the UPS is associated a variety of neurodegenerative diseases. In this study, three inhibitors the UPS, ziram, clasto-lactacystin β-lactone (lactacystin) and G5 were employed to illuminate involvement of the UPS in long-term and short term plasticity in area CA1 of rat hippocampal slices. Ziram, lactacystin and G5 inhibits the E1 ubiquitin-activating enzyme, the proteasome and isopeptidases, respectively. It was found that UPS inhibition enhanced long-term plasticity, by specifically increasing the magnitude of long-term depression (LTD) and altered short term plasticity, measured with paired pulse facilitation (PPF), to varying degrees. These findings establish that the UPS may play a regulatory role in LTD and PPF, and the changes in PPF further indicate that the UPS may be acting presynaptically. Overall, the results suggest ubiquitination and proteasome-mediated proteolysis are important in both long-term and short-term plasticity.

The number of non-parasitic (brook) lamprey species in the genus Lampetra is underestimated since isolated populations are generally considered one species due to their relatively conserved body form. The phylogeographic and phylogenetic structure was estimated among and within Lampetra species along the Pacific coast of North America (presumed to represent Lampetra richardsoni; L. pacifica – which is currently regarded as a junior synonym of L. richardsoni; L. ayresii; and L. hubbsi) using up to three mitochondrial and three nuclear genetic markers. These data show that L. richardsoni as currently recognized is polyphyletic when lampreys (some of which show up to 8 K2P% sequence divergence) from Siuslaw River and Fourmile Creek (Oregon) and Mark West, Paynes, and Kelsey creeks (California) are included; Lampetra pacifica is a valid species; the population from Kelsey Creek almost certainly represents a new species; and those from Siuslaw, Fourmile, and Mark West may also be distinct species.

No description available.

Diencephalic amnesia is thought to be the result of damage to a single thalamic structure that is responsible for the memory impairment. However, an alternative view is that different thalamic structures contribute to the memory impairment in subtly different ways. Paired-associate learning is one important measure of learning and memory that is highly sensitive to disruption in people with amnesia or dementia. The current study will investigate the influence of lesions to two thalamic subregions, the anterior thalamic nuclei (AT) and the lateral thalamic nuclei (LT) in an object-odour paired associate learning task. Each of these subregions has been suggested by the literature as critical for amnesia after thalamus injury. The current study does not involve a place/ space component. Both AT and LT lesions caused impairments in the object-odour paired associate task, but not in the simple discrimination tasks. The results of this study provide new evidence to suggest that the anterior thalamic region may be responsible for more than spatial memory processing. This result is inconsistent with those of Aggleton & Brown (1999) that consider the AT to be part of an 'extended hippocampal system'. The deficits observed from LT lesions in this study provide new insight into the lateral thalamic region's role in pattern processing.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 56-58).

Thesis (Ph. D.)--UCLA, 2008. / Vita. Description based on print version record. Includes bibliographical references (leaves 197-220).