Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 109-112). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1997. / Typescript. Vita. Includes bibliographical references (leaves 109-112). Also available on the Internet.

Thesis (Ph.D.)--Georgetown University, 2008. / Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 198-229).

This study investigated spatial learning in Caenorabditis elegans; the ability to associate reinforcing cues with a location. Naive, wildtype C. elegans were trained in a microfluidic t-maze in the presence of diacetyl (a volatile attractant associated with food) and subsequently tested to see if they could associate diacetyl with one arm of the t-maze. 70-80% of the subjects chemotaxed towards diacetyl during training phase, but they randomly chose left or right when diacetyl was absent (number of subjects that chose diacetyl being under 65%). From our experiments, it is unlikely that the worms are associating diacetyl with one arm of the t-maze, but appears to be using some component of the atmosphere as a cue.

Sensory information is processed and encoded by neural networks. In order to understand how the nervous system is able to rapidly integrate and store sensory information, knowledge of the connections and properties of the neurons in these circuits is required. The fruit fly Drosophila melanogaster provides a particularly powerful species to investigate the neural circuits of the olfactory system because in addition to possessing a simple olfactory system amenable to circuit analysis, a host of genetic reagents are available, including the GAL4-UAS system for targeted gene expression. The mushroom bodies, paired structures historically implicated in olfactory learning and memory, receive olfactory information at the mushroom body calyx from second-order olfactory projection neurons (PNs). Within the calyx, individual PN axonal boutons are surrounded by dendritic arborizations from intrinsic Kenyon cells (KCs) and each tiny cluster constitutes a single microglomerulus. Cells that connect the calyx with other areas of the brain, extrinsic neurons (ENs), also contribute to microglomeruli. Most of these contain the neurotransmitter, GABA, and are presumed to be inhibitory. In this study, the synaptic characteristics, neural circuits, and plasticity of calycal cells have been investigated using a combination of serial section electron and confocal microscopy. The findings reveal several new features of the circuits in the calyx: 1) The calyx contains three ultrastructurally distinct types of PN boutons that are heterogeneous in shape and exhibit subtle differences in synaptic densities. 2) All PN boutons form both ribbon and non-ribbon synapses, and from their smaller size and fewer postsynaptic partners, non-ribbon synapses may possibly become converted to ribbon synapses after activity; the olfactory signal may then be transmitted more strongly and efficiently at ribbon synapses. 3) PN boutons with an electron-dense cytoplasm have the most ribbon synapses per unit area of membrane as well as the highest ratio of ribbon to non-ribbon synapses, and thus may be more active and efficient than other boutons. 4) KC neurites are not exclusively postsynaptic in the calyx and can form occasional ribbon synapses, the functional interpretation of which awaits identification of their postsynaptic partners and vesicle contents. 5) Each PN bouton may contribute input to a single dendritic KC claw at about three presynaptic sites. For the postsynaptic side, a single claw receives input from individual presynaptic sites that must be highly redundant. 6) There may be important processing of the olfactory signal by local circuits formed by ENs in the calyx; ENs form synaptic connections with PNs, KCs, and other ENs. 7) Extensive serial synapses link EN terminals into a network, presumed to be GABAergic and inhibitory, that extends between microglomeruli and may be autaptic. 8) The structure and synaptic connectivity of microglomeruli may undergo changes after adult emergence. 9) vGAT and GAD1-GAL4 lines drive ectopic expression of marker genes in KCs and are not reliable reporters of GABA-positive cells. 10) Previously identified calycal ENs (MB-C1, MB-C2/C3, MB-CP1) are not immunopositive for GAD1, a marker of GABA-containing cells. 11) A network of ENs expressing a GABA phenotype differently innervates anatomically and functionally discrete areas of the honeybee calyx, and in addition the density of innervation may change with alterations in age and/or experience.

Many molecules and the complex interactions between them underlie plasticity in the cerebellum. However, the exact relationship between cerebellar plasticity and the different signalling cascades remains unclear. Calcium-calmodulin dependent protein kinase II (CaMKII) regulates many forms of synaptic plasticity, but very little is known about its function during plasticity induction in the cerebellum. The aim of this thesis is to contribute to a better understanding of the molecular mechanisms that regulate the induction of synaptic plasticity in cerebellar Purkinje cells (PCs). The focus of the thesis is to investigate the role of CaMKII isoforms in the bidirectional modulation of plasticity induction at parallel fibre (PF)-PC synapses. For this investigation, computational models that represent the CaMKII activation and the signalling network that mediates plasticity induction at these synapses were constructed. The model of CaMKII activation by calcium-calmodulin developed by Dupont et al (2003) replicates the experiments by De Koninck and Schulman (1998). Both theoretical and experimental studies have argued that the phosphorylation and activation of CaMKII depends on the frequency of calcium oscillations. Using a simplified version of the Dupont model, it was demonstrated that the CaMKII phosphorylation is mostly determined by the average calcium-calmodulin concentration, and therefore depends only indirectly on the actual frequency of calcium oscillations. I have shown that a pulsed application of calcium-calmodulin is, in fact, not required at all. These findings strongly indicate that the activation of CaMKII depends on the average calcium-calmodulin concentration and not on the oscillation frequency per se as asserted in those studies. This thesis also presents the first model of AMPA receptor phosphorylation that simulates the induction of long-term depression (LTD) and potentiation (LTP) at the PF-PC synapse. The results of computer simulations of a simple mathematical model suggest that the balance of CaMKII-mediated phosphorylation and protein phosphatase 2B (PP2B)-mediated dephosphorylation of AMPA receptors determines whether LTD or LTP occurs in cerebellar PCs. This model replicates the experimental observations by Van Woerden et al (2009) that indicate that CaMKII controls the direction of plasticity at PF-PC synapses. My computer simulations support Van Woerden et al’s original suggestion that filamentous actin binding can enable CaMKII to regulate bidirectional plasticity at these synapses. The computational models of intracellular signalling constructed in this thesis advance the understanding of the mechanisms of synaptic plasticity induction in the cerebellum. These simple models are significant tools for future research by the scientific community.

The theory of relational complexity (RC) developed by Halford and his associates (Halford et al., 1998a) proposes that, in addition to the number of unique entities that can be processed in parallel, it is the structure (complexity) of the relations between these entities that most appropriately captures the essence of processing capacity limitations. Halford et al. propose that the relational complexity metric forms an ordinal scale along which both task complexity and an individual's processing capacity can be ranked. However, the underlying quantitative structure of the RC metric is largely unknown. It is argued that an assessment of the measurement properties of the RC metric is necessary to first demonstrate that the scale is able to rank order task complexity and cognitive capacity in adults. If in addition to ordinal ranking, it can be demonstrated that a continuous monotonic scale underlies the ranking of capacity (the natural extension of the complexity classification), then the potential to improve our understanding of adult cognition is further realised. Using a combination of cognitive psychology and individual differences methodologies, this thesis explores the psychometric properties of RC in three high level reasoning tasks. The Knight-Knave Task and the Sentence Comprehension Task come from the psychological literature. The third task, the Latin Square Task, was developed especially for this project to test the RC theory. An extensive RC analysis of the Knight-Knave Task is conducted using the Method for Analysis of Relational Complexity (MARC). Processing in the Knight-Knave Task has been previously explored using deduction-rules and mental models. We have taken this work as the basis for applying MARC and attempted to model the substantial demands these problems make on limited working memory resources in terms of their relational structure. The RC of the Sentence Comprehension Task has been reported in the literature and we further review and extend the empirically evidence for this task. The primary criterion imposed for developing the Latin Square Task was to minimize confounds that might weaken the identification and interpretation of a RC effect. Factors such as storage load and prior experience were minimized by specifying that the task should be novel, have a small number of general rules that could be mastered quickly by people of differing ages and abilities, and have no rules that are complexity level specific. The strength of MARC lies in using RC to explicitly link the cognitive demand of a task with the capacity of the individual. The cognitive psychology approach predicts performance decrements with increased task complexity and primarily deals with aggregated data across task condition (comparison of means). It is argued however that to minimise the subtle circularity created by validating a task's complexity using the same information that is used to validate the individual's processing capacity, an integration of the individual differences approach is necessary. The first major empirical study of the project evaluates the utility of the traditional dual-task approach to analyse the influence of the RC manipulation on the dual-task deficit. The Easy-to-Hard paradigm, a modification of the dual-task methodology, is used to explore the influence of individual differences in processing capacity as a function of RC. The second major empirical study explores the psychometric approach to cognitive complexity. The basic premise is that if RC is a manipulation of cognitive complexity in the traditional psychometric sense, then it should display similar psychometric properties. That is, increasing RC should result in an increasing monotonic relationship between task performance and Fluid Intelligence (Gf) - the complexity-Gf effect. Results from the comparison of means approach indicates that as expected, mean accuracy and response times differed reliably as a function of RC. An interaction between RC and Gf on task performance was also observed. The pattern of correlations was generally not consistent across RC tasks and is qualitatively different in important ways to the complexity-Gf effect. It is concluded that the Latin Square Task has sufficient measurement properties to allows us to discuss (i) how RC differs from complexity in tasks in which expected patterns of correlations are observed, (ii) what additional information needs to be considered to assist with the a priori identification of task characteristics that impose high cognitive demand, and (iii) the implications for understanding reasoning in dynamic and unconstrained environments outside the laboratory. We conclude that relational complexity theory provides a strong foundation from which to explore the influence of individual differences in performance further.

The role of discourse in the construction of institutional and academic knowledge is now recognised within a wide variety of theoretical perspectives, including social constructionism, the sociology of scientific knowledge, the rhetoric of inquiry and discursive psychology. The purpose of this study was to examine the ways in which such discursive knowledge construction practices occur in relation to psychological phenomena. The site of this investigation was the highly contentious debate surrounding the reality of repressed/recovered memories of childhood sexual abuse. Ten 'popular' psychology texts (five supporting the concept of recovered memories and five questioning it) were discursively and rhetorically analysed in order to gain an understanding of how the authors of these texts deployed arguments to support their own positions and undermine those of their opponents. Five broad rhetorical resources were identified as being prominent in the texts, each of which was examined in detail to determine more specifically the source of their persuasive power. The five resources included authorial credibility, definitions, science, history and personal experience. Despite the meta-rhetoric surrounding the debate, which suggests that it is essentially an argument between researchers (drawing on scientific evidence) and clinicians (drawing on clinical experience), what was apparent was that all of these resources were utilised to varying degrees to support both pro- and anti- recovered memory positions. This analysis suggested that a reasonably structured set of discursive resources were available for making arguments about the nature of psychological phenomena. Furthermore, when given the opportunity, rhetors utilised as many of these resources as possible in order to produce a convincing argument, even when this resulted in inconsistencies within their texts. It was concluded that in the memory debate, the demands of the rhetorical imperative (to persuade the audience) often appear to be paramount, and should not be discounted by those seeking to understand this difficult and often distressing topic.