Thesis (Ph. D.)--Rutgers University, 2010. / "Graduate Program in Integrative Neuroscience." Includes bibliographical references (p. 100-132).

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Co-Chair: Butera, Robert; Committee Co-Chair: Paninski, Liam; Committee Member: Isbell, Charles; Committee Member: Rozell, Chris; Committee Member: Stanley, Garrett; Committee Member: Vidakovic, Brani.

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

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Efficient search benefits from persistent exposure to the statistical liklihoods that underpin object locations, such that time and energy expenditure tends be minimal. Inspections are made towards areas where objects are most likely to appear or have previously produced successful results. Experimentally, this phenomena has been named the ‘probability cueing effect’, and has predominantly been studied using visual search paradigms. In this context, participants bias their search towards locations where a target frequently appears, but they do not express any conscious awareness of doing so. However, in real-world tasks, it is much harder for spatial inferences to be made, with additional factors to be considered, such as consistency in where search is inititated. When the cue is learnt, it is instead consciously acknowledged. The research within this Thesis investigated search in an additional context: virtual, representational space. Probability cueing was successful but only when the environment was of minimal immersion. Parallel to visual search, participants did not express an awareness of the cue suggesting that physical movement is important for conscious awareness of learning. The transfer of probability cueing across virtual to real space was also examined, although an effect was not established. This finding has important applied implications, when considering that virtual environments are used throughout many industries as training tools. To conclude, three experiments investigated the underlying neural system that may support probability cueing, specifically the right parietal cortex. Much research has shown that this area plays a key role in allocating spatial attention across hemifields, but its input for probability cueing has not yet been investigated. These experiments used transcranial anodal (excitatory) and cathodal (inhibitory) stimulation to moduate this brain area. In a visual, 2D task and a 3D virtual environment task, search efficiency was modulated, with both stimulation types improving general search profiles. In a real-world task, search efficiency was again modulated, as well as probability cueing with stimulation interacting with the high-probability hemispace. Together these studies provide a comprehensive understanding of probability cueing under various environmental search constraints, and the role of the right parietal cortex in the guidance of this search strategy.

In a series of 6 experiments this thesis aimed to explore how the processing of peri-personal space might be affected by changes in sensory information. Previous research has shown that when stimuli is presented within peri-personal space it is processed differently, specifically it has been suggested that there is a prioritisation of space to the area around the hands. If there is a change in processing for the space around us, how might this be affected when interacting with a virtual or augmented environment in which sensory information may be altered? To investigate these changes the MIRAGE mediated reality system was used in which a live video recording of the hand is displayed in real-time in its spatially veridical location, and allows the manipulation of this image and sensory modalities separately. This allowed a more detailed evaluation of previous theories by testing spatial, temporal, and fidelity changes to the hand. Results showed spatial changes between seen and felt hand positions to significantly alter the processing of stimuli presented near and far from the hands. Specifically it was illustrated that a gradual separation between the visual and real hand locations seemed to first create an expansion in the visual receptive fields of bimodal visual-tactile neurons, and second, suggested a remapping of the limbs location to somewhere between the separate representations. Furthermore the application of transcranial direct current stimulation (tDCS), specifically cathodal stimulation, appears to have disrupted proprioceptive feedback, however these effects require further investigation and replication. Results also showed how temporal lag can impair performance on a movement task, while changes in hand fidelity did not significantly alter the processing of peri-personal space. In summary, the experiments presented in this thesis illustrate that spatial changes between seen and felt hand positions significantly alter the way we process space around the hands, and suggest that previous theories need to be re-evaluated and possibly combined to better represent how these changes occur. The findings also have implications for which factors may be most important when exploring how we process peri-personal space in an augmented or virtual environment.

Medio-lateral narrowing (convergence) and anterior-posterior elongation (extension) are two of the most important cell movements of the gastrulation period leading to the formation of embryonic body axis. In vertebrates, convergence and extension (CE) cell movements are regulated by the non-canonical Wnt/Planar cell polarity (PCP) signalling pathway which requires the activation of its downstream effectors, Rho GTPases. DEF6 and SWAP70 are guanine nucleotide exchange factors (GEFs) catalysing the activation of Rho GTPases to regulate the re-arrangement of actin cytoskeleton, cell polarity and cell movements. Although it has been shown that the zebrafish orthologous, Def6a and Swap70b, act downstream of Wnt5b or Wnt11 signalling pathway, respectively, regulating the CE cell movements during gastrulation, little is known about the underlying molecular mechanisms and direct downstream targets of Def6a and Swap70b. To further elucidate the function of def6a and swap70b within the non-canonical Wnt/PCP signalling pathway, Transcription Activator-Like Effector Nucleases (TALENs)-induced mutagenesis was employed to establish knock-out mutant lines lacking either def6a (qmc811), swap70b (qmc809) or both (qmc813). Phenotypic and whole-mount in situ hybridisation analyses have revealed that the anterior movement and the convergence of the lateral mesendodermal and ectodermal cells were severely impaired in def6a and/or swap70b-deficient zebrafish embryos, indicating that def6a and swap70b are required for normal CE cell movements during gastrulation. Ectopic expression of Cdc42 GTPase robustly rescued the CE cell movement defects in both def6aqmc811/qmc811 and swap70bqmc809/qmc809 homozygous mutant lines whereas ectopic expression of RacI robustly rescued CE cell movement defects only in swap70bqmc809/qmc809 homozygous mutant line, suggesting that Def6a and Swap70b acts upstream of Cdc42 and Cdc42/RacI respectively. Elevated expression of wnt5b and wnt11 detected in the mutant lines indicated that abrogation of def6a and swap70b functions interfered with Cdc42/RacI-mediated Jnk activation that negatively regulates expression of wnt11 and perhaps wnt5b. In adult def6a and/or swap70b-deficient fish, a decreased number of myeloid population was observed, suggesting that both proteins are required for balanced cell differentiation during haematopoiesis. Generation of the double homozygous mutant line revealed that def6a and swap70b act in a partially redundant manner during zebrafish embryogenesis and in a non-redundant manner during haematopoiesis. DEF6 is highly expressed in T cells and plays an immunoregulatory role in cell polarity-induced immunological synapse (IS) formation, T cell receptor (TCR) signalling, T cell activation, differentiation and inflammatory responses. Recently, it has been shown that DEF6 may also be involved in the mRNA surveillance and translation. However, the molecular mechanisms that it may be involved in and its interactors in T cells are still unknown. Hence, a novel method, BioID, which enables the promiscuous biotinylation of proximal and interacting proteins of a target protein in mammalian cells, was adapted to identify DEF6 interactome in Jurkat T cells. Notably, in vivo BioID-DEF6 fusions yielded 127 clusters of interacting and vicinal proteins, including 2 known binding partners, Rac2 and PKC and 1 known close proximity partner, PABP. GO-term classification of the identified proteins showed that the proteins are enriched not only in actin cytoskeleton organisation and mRNA translation, but also in transcription, mRNA splicing/processing, protein folding/modification and metabolic processes. Co-localisation of DEF6 with Coronin1A (CORO1A), an actin cytoskeleton regulator during IS formation, in resting and activated cells provided proof of principle for the interactome analysis suggesting that DEF6 is a multifunctional protein involved in the regulation of cytoskeletal organisation, transcription, mRNA splicing, protein folding/processing and metabolic processes.

Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Models of the neural basis of visually guided behavior suggest that the mammalian brain has two independent visual systems: one involved in pattern vision, and the other involved in orienting to visual stimuli. Orienting was measured in this series of studies by examining both the thirsty rat's ability to disrupt licking in response to the presentation of visual and auditory displays and the animal's head and postural responses to the displays. Habituation of orienting behavior with repeated presentation of a display, and dishabituation to the subsequent introduction of changes in it were also examined. The effect on this behavior of variously sized cortical and subcortical lesions of the visual system and the influence of extrinsic and intrinsic variables were assessed. The investigation revealed that lesions of the superior colliculus do not result in visual agnosia or the inability to perform the appropriate motor responses involved in orienting; rather, while the orienting response is available in the behavioral repertoire of the lesioned animal, it is not always emitted in response to the visual displays that the intact animals treat as less salient. The superior colliculus lesioned animals do orient to and localize visual displays which are more salient for the intact animal. Further, the deficit in orienting to the "less" salient stimulus displays can be reduced or eliminated by changing the degree of water deprivation prior to testing and they are capable of using this display as a signal of shock. Lesions restricted to a very small portion of the lateral edges of the deep layers of the superior colliculus and the dorsal tegmentum had the same consequences as superior colliculus lesions, while lesions which included only the superficial layers of the superior colliculus did not. Lesions of the striate and extrastriate cortex did not significantly affect orienting behavior. Rats with lesions of the superficial or deep layers of the superior colliculus and rats with lesions including area 7 of cortex as well as the striate and extrastriate cortex, did,however, habituate more quickly than intact animals to the repeated presentation of the visual displays, and generally did not dishabituate in response to the changes in the visual displays. These findings suggest a relationship-between the cortex, the superficial layers, and the deep layers of the superior colliculus and the ability of animals to shift attention within a stimulus modality. The deep layers of the superior colliculus may also be important for shifts of attention between stimulus modalities (Jane, Levey, & Carlson, 1972). Overall, these results were discussed with regard to a possible modulating role of the superior-colliculus and cortex in orienting behavior and in terms of the parameters of orienting which must be taken into account in the development of an adequate model of the neural basis of orienting behavior. / Arts, Faculty of / Psychology, Department of / Graduate

Spatially structured bursts of propagating neural activity revealed in cortical slice experiments and in vivo tantalise many scientists on their possible functional mechanisms. Theoretical studies suggest waves with complex firing patterns afford a great capacity for the transmission of information across the brain. This thesis develops a framework for analysing the dynamics of such waves within spiking neuronal networks. We seek to investigate important questions concerning how the wave’s spatiotemporal voltage properties, propagation speed and spike time interval distributions depend on the underlying network structure and the intrinsic features of the neurons that make up the network. These are often difficult to extract with biophysically detailed network models. We therefore analyse simplified spiking networks of synaptically connected neurons, capable of supporting a rich repertoire of propagating activity, yet, amenable to mathematical analysis. Useful information is then obtained on the dynamics of waves found in this network in relation to the model’s parameters. These results can be compared to the findings obtained from more detailed computational studies and experimental observations. Numerical simulations in discrete networks of integrate-and-fire neurons reveal localised bumps that can wander diffusively across the network. These wandering bumps are seen to evolve into persistent synchronous coherent propagating structures, where neurons fire multiple times as the wave envelope passes over. We call these structures multiple-spike waves. An intrinsic feature of the neuron, describing how quickly neurons process synaptic current, is shown to be an important determinant in the emergent network activity. Waves with different number of spiking events co-exist across most parameter regimes, and with lateral-inhibition synaptic connectivity structure, can exhibit large variability in wave speed that has not been reported in studies of networks with purely excitatory connectivity. As a result, we investigate the interaction dynamics of multiple-spike waves on a large spatial domain. Here we find that multiple-spikes waves can merge to form a composite system, with greater complexity in the firing patterns, increasing the wave’s information content. Mathematical progress is made by studying a partial integro-differential equation that is equivalent to the discrete network as the number of neurons tends to infinity. We develop a method of solving the wave speed of the multiple spike waves and its set of spike-times, which then allows us to construct the network’s exact voltage and synaptic profiles and formulate a non-local eigenvalue problem to compute asymptotic stability. This is achieved by considering general perturbations around the wave’s firing times. An in-depth numerical study on the multiple-spike wave’s bifurcation structure is performed, uncovering various mechanisms behind propagation failure and how the wave’s dynamics depend on the network’s system parameters. The analysis of waves with a large number of spikes poses interesting questions regarding the existence of stationary bump solutions in the continuum limit. Uncertainty quantification is performed on waves, revealing how different types of uncertainty in system parameters influence the wave solutions statistical properties. This allows for predictions of the spatial regions of the waves profile most vulnerable to destabilisation. We finally analyse synaptically generated waves in a similar spiking network of Morris-Lecar neurons, where we find interesting transitions from single to double spike waves. Also, similar to what was seen in the integrate-and-fire network, the wave’s dynamics at the network level is strongly influenced by the neuron’s intrinsic features.