In the study of navigation, frequently it is assumed that navigation is accomplished using either an allocentric strategy based on a cognitive map, or an egocentric strategy based on stimulus response associations. Further, it is frequently assumed that individual navigators, or even entire genders, are only capable of navigating by one strategy or the other. The present study investigated whether individuals or genders were limited to a particular navigational strategy and whether both strategies might be learned or used at the same time. In the present study, undergraduate students were tested in a virtual Morris water maze that was modified to allow successful and efficient navigation using either an allocentric or an egocentric strategy. Learning trials on which the participants had to learn the location of the platform were alternated with probe trials on which participants would show which strategy they were using. At the end of testing, participants were given a series of tests to determine what knowledge they had acquired and which strategies they were capable of using. Results indicated that: a) most people preferred to navigate egocentrically in this maze, but some preferred to navigate allocentrically, b) people tended to use an egocentrically strategy first, but it was not a necessary step to learning to navigate allocentrically, c) people were better at their preferred strategy, d) people learned information about their non-preferred strategy, and e) those who preferred to navigate egocentrically could nevertheless learn to navigate allocentrically. Surprisingly, all of these results were true for both men and women, although women tended to prefer egocentric navigation at a higher rate than men, and men outperformed women when forced to navigate allocentrically. These results suggest it may be too simple to think of navigators as being capable of only a single navigational strategy or of learning only one strategy at a time. / Graduate

Opioid medications are medicine's best weapon against severe intractable pain, but prolonged use of these medications can be complicated by side effects like tolerance and mental clouding which, themselves, can be disabling. The present study examined the independent and combined effects of inflammatory pain and opioid medication on spatial memory for a well learned task in Sprague-Dawley rats. The Hargreaves method was used to verify the pain state of the animals after complete Freund's adjuvant injection and morphine treatment. Whereas pain had little effect on spatial memory, morphine had profound detrimental effects that persisted beyond the analgesic effectiveness of the drug. However, morphine-induced cognitive deficits were absent when morphine was provided to animals in chronic pain. Also, analgesic tolerance was significantly attenuated in these animals. Taken together, these results suggest that chronic pain activates a neural mechanism that antagonizes the unwanted effects of opioids.

No description available.

Anxiety disorders are one of the most prevalent mental disorders in the world. While normal anxiety serves as an important protective mechanism, pathological anxiety characteristic of an anxiety disorder is both maladaptive and disruptive. The majority of studies have focused on the neurotransmitter systems associated with the actions of known anxiety drugs. This focus may likely limit the exploration of mechanisms underlying anxiety disorders. This project aims to examine changes in gene expression that may underlie higher or lower levels of inherent anxiety. Using a well-established behavior test for anxiety, the elevated plus maze, we identified male Wistar rats exhibiting inherently high- or low-anxiety levels. Brain regions known to mediate anxiety, the amygdala, hippocampus and nucleus accumbens, were dissected and total mRNA isolated. The mRNA was converted to cDNA via reverse transcription-polymerase chain reaction (RT-PCR). Then, the cDNA was used in suppression subtractive hybridization, a technique used to compare two complete populations of cDNAs and identify cDNAs that are upregulated in one population in relation to the other. In this project suppression subtractive hybridization was used to compare high- and low-anxiety cDNA populations. The upregulated cDNAs were amplified in a PCR reaction that enables rare transcripts to be identified. The PCR products from the suppression subtractive hybridization were cloned and used to create two cDNA libraries for high- and low-anxiety related genes. These clones were sequenced to show over 1000 genes upregulated in high- and low-anxiety. The gene list was then subjected to bioinformatic analysis to identify one candidate to be studied in further detail. <p>The prion protein was identified as a potential candidate. Examination of the literature sparked an interest in studying other prion-like proteins, more specifically the cytoplasmic polyadenylation element binding protein (CPEB). The CPEB protein is a potent regulator of mRNA translation in both mature oocytes and the adult brain. While unphosphorylated the CPEB protein keeps specific mRNAs dormant in the cytoplasm. In its phosphorylated form CPEB catalyzes polyadenylation of the mRNA, leading to protein synthesis. p*PCR was used to show the presence of CPEB mRNA transcripts in the rat hippocampus. CPEB protein expression was examined in the brain samples isolated from control, high- and low-anxiety rats. It was found that CPEB was significantly upregulated in high- and low-anxiety rats compared to control. The protein expression of an upstream kinase, Aurora A kinase, and a downstream target, Calcium/Calmodulin Dependent Kinase II (CaMKII), was also investigated. The results from Aurora A kinase were inconclusive. CaMKII, on the other hand, was significantly upregulated in high-anxiety over both control and low-anxiety. These results suggest that CPEB may catalyze increased translation of mRNAs in high-anxiety while acting as a repressor of those same mRNAs in low-anxiety. <p>Recent studies have suggested that CPEB protein plays an important role in synaptic plasticity. The regulation of synaptic plasticity, and its impact on learning and memory, is believed to be a key mechanism behind the maintenance of anxiety disorders. Therefore the results of this study suggest a new molecular mechanism in the development of anxiety disorders.

Anxiety disorders are one of the most prevalent mental disorders in the world. While normal anxiety serves as an important protective mechanism, pathological anxiety characteristic of an anxiety disorder is both maladaptive and disruptive. The majority of studies have focused on the neurotransmitter systems associated with the actions of known anxiety drugs. This focus may likely limit the exploration of mechanisms underlying anxiety disorders. This project aims to examine changes in gene expression that may underlie higher or lower levels of inherent anxiety. Using a well-established behavior test for anxiety, the elevated plus maze, we identified male Wistar rats exhibiting inherently high- or low-anxiety levels. Brain regions known to mediate anxiety, the amygdala, hippocampus and nucleus accumbens, were dissected and total mRNA isolated. The mRNA was converted to cDNA via reverse transcription-polymerase chain reaction (RT-PCR). Then, the cDNA was used in suppression subtractive hybridization, a technique used to compare two complete populations of cDNAs and identify cDNAs that are upregulated in one population in relation to the other. In this project suppression subtractive hybridization was used to compare high- and low-anxiety cDNA populations. The upregulated cDNAs were amplified in a PCR reaction that enables rare transcripts to be identified. The PCR products from the suppression subtractive hybridization were cloned and used to create two cDNA libraries for high- and low-anxiety related genes. These clones were sequenced to show over 1000 genes upregulated in high- and low-anxiety. The gene list was then subjected to bioinformatic analysis to identify one candidate to be studied in further detail. <p>The prion protein was identified as a potential candidate. Examination of the literature sparked an interest in studying other prion-like proteins, more specifically the cytoplasmic polyadenylation element binding protein (CPEB). The CPEB protein is a potent regulator of mRNA translation in both mature oocytes and the adult brain. While unphosphorylated the CPEB protein keeps specific mRNAs dormant in the cytoplasm. In its phosphorylated form CPEB catalyzes polyadenylation of the mRNA, leading to protein synthesis. p*PCR was used to show the presence of CPEB mRNA transcripts in the rat hippocampus. CPEB protein expression was examined in the brain samples isolated from control, high- and low-anxiety rats. It was found that CPEB was significantly upregulated in high- and low-anxiety rats compared to control. The protein expression of an upstream kinase, Aurora A kinase, and a downstream target, Calcium/Calmodulin Dependent Kinase II (CaMKII), was also investigated. The results from Aurora A kinase were inconclusive. CaMKII, on the other hand, was significantly upregulated in high-anxiety over both control and low-anxiety. These results suggest that CPEB may catalyze increased translation of mRNAs in high-anxiety while acting as a repressor of those same mRNAs in low-anxiety. <p>Recent studies have suggested that CPEB protein plays an important role in synaptic plasticity. The regulation of synaptic plasticity, and its impact on learning and memory, is believed to be a key mechanism behind the maintenance of anxiety disorders. Therefore the results of this study suggest a new molecular mechanism in the development of anxiety disorders.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 22, 2010). Thesis advisor: Dr. Marjorie Skubic. Includes bibliographical references.

This research develops a memory model capable of performing in a human-like fashion on a maze traversal task. The model is based on and retains the underlying ideas of Minerva 2 but is executed with different mathematical operations and with some added parameters and procedures that enable more capabilities. When applied to the same maze traversal task as was used in a previous experiment with human subjects, the performance of a maze traversal agent with the developed model as its memory emulated the error rates of the human data remarkably well. As well, the maze traversal agent and memory model successfully emulated the human data when it was divided into two groups: fast maze learners and slow maze learners. It was able to account for individual differences in performance, specifically, individual differences in the learning rate. Because forgetting was not applied and therefore all experiences were flawlessly encoded in memory, the model additionally demonstrates that error can be due to interference between memories rather than forgetting. / Thesis (Master, Computing) -- Queen's University, 2008-06-04 13:39:38.179

The experiments reported in the present thesis investigated the effects of lesions to the anterior nuclei of the thalamus (ATN) on the acquisition of two spatial, working memory tasks performed on the eight-arm radial maze. In the task used in Experiment 1 and 2, the animals were required to discriminate and remember all the eight arms of the maze simultaneously. Lesions of the ATN produced impairments in the acquisition of this task, but the degree of impairment depended on the amount of damage within this region. In the task used in Experiment 3, the animals were required to discriminate and remember only two arms at once. Lesions of the ATN were shown to impair its acquisition even though performance was facilitated by the addition of visual intra-arms cues. These experiments suggest that the ATN may be involved in spatial learning and in the retention of non-specific information over time.

Research on the neural and cognitive basis of spatial navigation over the last 30 years has been largely guided by cognitive map theory and many of the studies have used a standardized procedure in a single task, the Morris Water Maze (MWM). Although this theory proposes that acquisition of place knowledge should be very rapid, little evidence has been provided to support this point. The present study investigates the possibility that a new procedure for measuring place knowledge in the MWM will show that place learning is faster than previously shown. In a virtual MWM with a fixed goal location, participants were given pairs of standard learning trials plus new explicit probe trials in which they were directed to go to where they found the goal on the immediately preceding trial. The distance between their estimate and the actual location was measured as “Place Error”. Results indicated that Place Errors were surprisingly small after just one learning trial and were equivalent for females and males. These findings provide new evidence for the fast learning proposed by cognitive map theory and demonstrate the value of this new method for measuring place learning. / Graduate

The role of the pedunculopontine tegmental nucleus (PPTg) in motivation and cognitive functions is controversial. In order to clarify the involvement of this nucleus in learning, rats with N-methyl-D-Aspartate (NMDA) lesions to the PPTg were tested on the acquisition of a delayed non-matching to position task (DNMP) performed in a T-maze. Unlike sham-lesioned rats, animals with PPTg lesions did not learn the task. Analysis of the behavior displayed by the lesions animals, however, suggested that these rats suffered from elevated emotionality or arousal, rather than from learning deficits. This hypothesis was confirmed by demonstrating that the anxiolytic compound diazepam (1 mg/kg) normalized the performance of the PPTg-lesioned rats on the DNMP task and reduced the indices of anxiety displayed by animals with PPTg lesions when tested on the elevated plus maze. / These results suggested the possibility that the motivational impairments reported to be induced by PPTg lesions, could also be an artifact of lesion-induced elevation of anxiety or arousal. Thus, in order to verify this hypothesis, it was tested whether diazepam would modify the expression of conditioned place preference (CPP) to morphine and amphetamine in animals with NMDA-induced lesions to the PPTg. Diazepam reversed the effects of the lesion on a morphine CPP but not on an amphetamine CPP. A series of experiments, aimed at characterizing the effects of diazepam on morphine and amphetamine reinforcement in normal rats, showed that diazepam, either systemic or injected in the nucleus accumbens, blocks the reinforcing effects of amphetamine but has no effect on the reinforcing effects of morphine. These results suggest that impairments in CPP learning caused by PPTg lesions do not result from motivational deficits, but are caused by elevated emotionality or abnormal arousal.