Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 304-332).

Thesis (M. S.)--Biomedical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: James K. Rilling; Committee Chair: Xiaoping Hu; Committee Member: Shella Keilholz; Committee Member: Todd M. Preuss.

Thesis--University of Florida. / Description based on print version record. Typescript. Vita. Includes bibliographical references (leaves 84-89).

Thesis (Ph. D.)--University of Chicago, Dept. of Ophthalmology and Visual Science, March 2001. / Includes bibliographical references. Also available on the Internet.

In order to understand biological intelligence I wanted to map the simplest example that could still demonstrate learning. Learning, or classical conditioning, has long been shown to occur in decapitated insects, hence this was a logical target, specifically the most studied insect, the fruit fly (Drosophila melanogaster). This learning occurs in the insect equivalent of the spinal cord, referred to as the ventral nervous system (VNS). The initial task was to resolve the gross neuroanatomy of the VNS. Standardising the neuroanatomical regional boundaries into 3D painted domains, clarifying textural descriptions, as well as matching the literature synonyms, were all combined into the Drosophila nomenclature. This enables existing knowledge, from the literature, to be easily queried as well as providing a basis for future additions. These clarified anatomical definitions were agreed by a workshop of researchers with experience in the VNS. Definitions will be published to form the basis for a more detailed nomenclature to be developed upon. In order to combine 3D images taken from different flies, a template was chosen, and an alignment pipeline tool devised. This alignment pipeline enabled samples of secondary lineages, that make up the bulk of the neurons in the VNS, to be aligned. This lineage atlas provided fixed internal boundary points for the neuroanatomy to be defined against. Previous work has provided detailed information on these lineages, as well as showing their likely homologous relationship as a gross functional unit within behavioural circuits. By constructing a spatial atlas of these lineages, a gross connection plan can be devised, targeting future research. This lineage atlas, in combination with NBLAST, enables the identification of single neurons to their developmental origin simply by using their morphology. The template with neuroanatomical definitions has been made publicly available via VirtualFlyBrain.org (VFB) and FlyBase.org. The alignment pipeline has been made available via a web interface for researchers to align their own data to the any of the VFB templates. This project provides an anatomical and developmental gross map of the VNS to enable greater development of the connectome.

Electrophysiological and neurochemical studies have been made in identifiable neurones in the central nervous systems of the gastropod molluscs Helix pomatia, Helix aspersa and Planorbis corneus. Using a technique of intracellular injection of radioactively labelled precursors, the neurotransmitter synthesising capabilities of several neurones have been investigated. Methods have been developed to ensure that radioactive metabolites detected within the nervous system following intracellular injection are within, and confined to, the soma axons, dendrites and terminals of the injected neurones. The results demonstrate that, with one exception some identifiable neurones possess the ability to synthesise either 3H-5-hydroxytryptamine from 3H-tryptophan and 3H-5-hydroxytryptophan or 3H-acetylcholine from 3H-choline but not both transmitters from their precursors. The exception to this observation is the giant serotonin-containing neurones of Helix pomatia and Helix aspersa which can synthesise both 3H-5-hydroxytryptamine and 3H-acetylcholine from their precursors. Moreover this study has shown that both newly synthesised transmitters in the Helix serotonin-containing neurones are transported to the synaptic terminals of the neurone and are probably released there. Thus this neurone appears to be at variance with the concept that a neurone can utilise only one transmitter substance (Dale's Principle). The final part of the thesis is a study of an identifiable -5-hydroxytryptamine-containing neurone in the right pedal ganglion of Planorbis corneus. This neurone has been extensively characterised by neuroanatomical, pharmacological and electrophysiological methods with a view to determining whether it makes monosynaptic connections with other neurones in the central nervous system. Although no direct connections were observed the neurone did modulate spontaneous activity in other neurones. The role of 5-hydroxytryptamine as a neuromodulator is discussed.

No description available.

The distinctiveness of brain structures and circuits depends on interacting gene products, yet the organization of these molecules (the "transcriptome") within and across brain areas remains unclear. High-throughput, neuroanatomically-specific gene expression datasets such as the Allen Human Brain Atlas (AHBA) and Allen Mouse Brain Atlas (AMBA) have recently become available, providing unprecedented opportunities to quantify molecular neuroanatomy. This dissertation seeks to clarify how transcriptomic organization relates to conventional neuroanatomy within and across species, and to introduce the use of gene expression data as a bridge between genotype and phenotype in complex behavioral disorders. The first part of this work examines large-scale, regional transcriptomic organization separately in the mouse and human brain. The use of dimensionality reduction methods and cross-sample correlations both revealed greater similarity between samples drawn from the same brain region. Sample profiles and differentially expressed genes across regions in the human brain also showed consistent anatomical specificity in a second human dataset with distinct sampling properties. The frequent use of mouse models in clinical research points to the importance of comparing molecular neuroanatomical organization across species. The second part of this dissertation describes three comparative approaches. First, at genome scale, expression profiles within homologous brain regions tended to show higher similarity than those from non-homologous regions, with substantial variability across regions. Second, gene subsets (defined using co-expression relationships or shared annotations), which provide region-specific, cross-species molecular signatures were identified. Finally, brain-wide expression patterns of orthologous genes were compared. Neuron and oligodendrocyte markers were more correlated than expected by chance, while astrocyte markers were less so. The localization and co-expression of genes reflect functional relationships that may underlie high-level functions. The final part of this dissertation describes a database of genes that have been implicated in speech and language disorders, and identifies brain regions where they are preferentially expressed or co-expressed. Several brain structures with functions relevant to four speech and language disorders showed co-expression of genes associated with these disorders. In particular, genes associated with persistent developmental stuttering showed stronger preferential co-expression in the basal ganglia, a structure of known importance in this disorder.

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