The topic of this dissertation is the study of the emergence of higher-order correlations in recurrentlyconnected populations of brain cells.Neurons have been experimentally shown to form vast networks in the brain. In these networks, eachbrain cell communicates with tens of thousands of its neighbors by sending out and receiving electricalsignals, known as action potentials or spikes. The effect of a single action potential can propagate throughthe network and cause additional spikes to be generated. Thus, the connectivity of the neuronal networkgreatly influences the network's spiking dynamics. However, while the methods of action potentialgeneration are very well studied, many dynamical features of neuronal networks are still only vaguelyunderstood.The reasons for this mostly have to do with the difficulties of keeping track of the collective, non-linearbehavior of hundreds of millions of brain cells. Even when one focuses on small groups of neurons, all butthe most trivial questions about coordinated activity remain unanswered, due to the combinatorialexplosion that arises in all questions of this sort. In theoretical neuroscience one often needs to resort tomathematical models that try to explain the most important dynamical phenomena while abstractingaway many of the morphological features of real neurons.On the other hand, advances in experimental methods are making simultaneous recording of largeneuronal populations possible. Datasets consisting of collective spike trains of thousands of neurons arebecoming available. With these new developments comes the possibility of finally understanding the wayin which connectivity gives rise to the many interesting dynamical aspects of spiking networks.The main research question, addressed in this thesis, is how connectivity between neurons influences thedegree of synchrony between their respective spike trains. Using a linear model of spiking neurondynamics, we show that there is a mathematical relationship between the network's connectivity and theso-called higher-order cumulants, which quantify beyond-chance-level coordinated activity of groups ofneurons. Our equations describe the specific connectivity patterns that give rise to higher-ordercorrelations. In addition, we explore the special case of correlations of third-order and find that, in large,regular networks, it is the presence of a single subtree that is responsible for third-order synchrony.In summary, the results presented in this dissertation advance our understanding of how higher-ordercorrelations between spike trains of neurons are affected by certain patterns in synaptic connectivity.Our hope is that a better understanding of such complicated neuronal dynamics can lead to a consistenttheory of the network's functional properties. / <p>QC 20161003</p>

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

This study uses a conductance-based computer simulation to test the feasibility of a mechanism underlying a newly-described dynamic form of neuromodulation, called spike-timing dependent neuromodulation (STDN). In the mollusc, Tritonia diomedea, it was recently found that a serotonergic neuron (called DSI) alters the synaptic strength of another neuron (VSI-B) in a temporally biphasic-bidirectional manner, with an initial potentiation followed by prolonged synaptic depression (Sakurai and Katz 2003). Physiological evidence suggested that the depression phase is due to serotonin enhancing the A-current in VSI-B, thereby causing spike-narrowing or a decrease in spike amplitude, and thus a decrease in transmitter release. We sought to test the feasibility of this mechanism by developing a conductance-based model of VSI-B using a Hodgkin-Huxley style simulation with a minimal number of ion conductances: A-current, delayed rectifier potassium, fast sodium, and leak channels. From our model, we conducted simulations in order to study how the spike shape of the VSI-B action potential changes as the A-current conductance is enhanced, from which we are able to predict the amount of depression in the post-synaptic cell. Our model indicates that the depression due to the narrowing of the spike with A-current enhancement is sufficient to account for the empirically observed depression during STDN, although it suggests a greater effect of serotonin at the terminals than is observed in the soma. Additionally, the model suggested that the slow inactivation kinetics of the A-current cannot explain the dynamics of the depression phase of STDN. These modeling results suggest that serotonergic modulation of the A-current plays a role in STDN but does not account for its dynamics.

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

Recently, a novel protein family, named as neural regeneration peptides (NRPs), was predicted across the rat, human and mouse genomes by one of my supervisors, Dr. Sieg. Synthetic forms of these proteins have been previously shown to act as potent neuronal chemoattractants and have a major role in neural regeneration. In light of these properties, these peptides are key candidates for drug development against an array of neurodegenerative disorders. The aim of this PhD project was to provide confirmation of the existence of a member of the NRP coding gene family, annotated in the mouse genome. This gene, called mouse frameshift nrp (mouFSnrp), was hypothesised exist as a -1bp frameshift to another predicted gene AlkB. This project involved the identification of the mouFSnrp gene, and the characterisation of its expression pattern and ontogeny during mouse neural development. Through the work described in this thesis, the mouFSnrp gene was identified in mouse embryonic cortical cultures and its protein coding gene sequence was verified. mouFSnrp expression was shown to be present in neural as well as non-neural tissues, via RT-PCR. Using non-radioactive in situ hybridisation and immunohistochemical colocalisation studies, interesting insights into the lineage and ontogeny of mouFSnrp expression during brain development were revealed. These results indicate that mouFSnrp expression originates in neural stem cells of the developing cortex, and appears to be preferentially continued via the radial glial lineage. mouFSnrp expression is carried forward via the neurogenic radial glia into their daughter neuronal progeny as well as postnatal astrocyte. In the postnatal brain, mouFSnrp gene transcripts were also observed in the olfactory bulb and the hippocampus, both of which are known to have high neurogenic potential. In general, the radial glial related nature of mouFSnrp expression appears to be a hallmark of the mouFSnrp expression pattern through out neural development. This thesis provides the first confirmation of the existence of a completely novel gene, mouFSnrp, and its putative -1 translational frameshifting structure. Further, preliminary data presented in this thesis regarding the mouFSnrp in situ expression pattern during mouse brain development may suggest a key role of the gene in neuronal migration and neurogenesis in mice. / FRST Bright Futures Enterprise Fellowship

Thesis (Ed.D.)--University of Tulsa, 1974. / Bibliography: leaves 115-124.

Thesis (Ph.D.)-- University of Adelaide, Dept. of Cytogenetics and Molecular Genetics, 2000. / Copies of author's previously published articles inserted. Errata sheets pasted onto front end papers. Bibliography: leaves 156-182.

Thesis (M.S.)--University of Missouri-Columbia, 2006. / Title from title screen of research.pdf file (viewed on December 22, 2006). The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2006" Includes bibliographical references.