No description available.

Epileptogenesis is the complex process of the brain developing epileptic acitivity. Due to the role of glutamate and the hippocampus in synaptic plasticity a dysregulation in glutamate neurotransmission and hippocampal dysfunction are implicated in the process of epileptogenesis. However, the exact causal factors that promote epileptogenesis are unknown. We study presynaptic proteins that regulate glutamate neurotransmission and their role in epileptogenesis. The presynaptic protein, tomosyn, is believed to be a negative regulator of glutamate neurotransmission; however, no one has studied the effects of this protein on glutamate transmission in vivo. Furthermore, evidence suggests that mice lacking tomosyn have a kindling phenotype. Thus, in vivo glutamate recordings in mice lacking tomosyn have the potential to elucidate the exact role of tomosyn in glutamate neurotransmission and its potential relationship to epileptogenesis. Here we used biosensors to measure glutamate in the dentate gyrus (DG), CA3, and CA1 of the hippocampus in tomosyn wild-type (Tom+/+), heterozygous (Tom+/-), and knock out (Tom-/-) mice. We found that, in the DG, that glutamate release increases as tomosyn expression decreases across genotype. This suggests that tomosyn dysregulation in the DG leads to an increase in glutamate release, which may explain why these mice have an epileptogenic phenotype.

No description available.

Two monoclonal antibodies (mabs), the newly generated mab anti-type I and the previously documented mab anti-zebrin II, were reacted with brainstem sections of two ostariophysan siluriforms, the gymnotoid Rhamphichthys rostratus and the siluroid Ictalurus punctatus. Mab anti-type I recognizes a 47 kD polypeptide present in the dendrites and soma of projection neurons. Mab anti-zebrin II recognizes a 36 kD polypeptide present throughout the neuronal cytoplasm, including the axon. Strongly type I immunopositive cells include all cerebellar Purkinje cells, pyramidal cells of the nucleus medialis, electrosensory lateral line lobe, and tectum, pacemaker relay cells, Mauthner neurons, lateral line ganglion cells, and cells of the reticular formation, lateral reticular nucleus, and inferior olive. Weakly reactive type I cells include neurons in the torus semicircularis, medial and efferent octavolateralis nuclei, magnocellular and lateral tegmentum, and motor neurons of the Vth, V I Ith, and Xth cranial nerves. All type I positive cells are projection neurons. Zebrin II expression is restricted to subsets of two cell types which also express the type I antigen -- Purkinje cells and developing acousticolateralis pyramidal cells. Both of these neurons develop from the region of the rhombic lip. Thus, the mutual expression of the type I antigen can be explained by the shared function of projection neurons, while the common expression of the zebrin II antigen may be due to a shared embryological lineage. / Department of Physiology and Health Science

Technological advancements have sparked discovery in biology, enabling important questions to be addressed experimentally at unprecedented depth and scale. One such advance, the development of large-scale approaches to study gene expression, has transformed the way we view the transcriptome. In recent years, these approaches have been applied to studies of alternative RNA splicing, a process where multiple distinct messenger RNAs can be generated from precursor transcripts to produce extensive transcriptomic diversity from a limited repertoire of genes. Global analyses have not only reinforced models initially based on single gene studies, they have also led to numerous insights into general principles governing the regulation and evolution of alternative splicing. In this thesis, I describe how I have combined both large-scale and focused approaches to study alternative splicing regulation during development and in an evolutionary context. Using microarray profiling and comparative genomics approaches, I describe the first large-scale comparative analysis of alternative splicing patterns between humans and chimpanzees. Next, I describe the discovery of a novel neural-specific RS domain splicing factor and the network of alternative exons it regulates to promote nervous system development in vertebrates. Finally, I describe the profiling of alternative splicing patterns during C. elegans development using splicing microarrays and high-throughput sequencing. In this latter study, I also describe two resources that facilitate the analysis of tissue- or cell type-specific splicing events, and enable the function of isoforms to be assessed in vivo. Collectively, these studies have shed light on how differential regulation of alternative splicing has contributed to the evolution of complexity and diversity in biological systems.

Technological advancements have sparked discovery in biology, enabling important questions to be addressed experimentally at unprecedented depth and scale. One such advance, the development of large-scale approaches to study gene expression, has transformed the way we view the transcriptome. In recent years, these approaches have been applied to studies of alternative RNA splicing, a process where multiple distinct messenger RNAs can be generated from precursor transcripts to produce extensive transcriptomic diversity from a limited repertoire of genes. Global analyses have not only reinforced models initially based on single gene studies, they have also led to numerous insights into general principles governing the regulation and evolution of alternative splicing. In this thesis, I describe how I have combined both large-scale and focused approaches to study alternative splicing regulation during development and in an evolutionary context. Using microarray profiling and comparative genomics approaches, I describe the first large-scale comparative analysis of alternative splicing patterns between humans and chimpanzees. Next, I describe the discovery of a novel neural-specific RS domain splicing factor and the network of alternative exons it regulates to promote nervous system development in vertebrates. Finally, I describe the profiling of alternative splicing patterns during C. elegans development using splicing microarrays and high-throughput sequencing. In this latter study, I also describe two resources that facilitate the analysis of tissue- or cell type-specific splicing events, and enable the function of isoforms to be assessed in vivo. Collectively, these studies have shed light on how differential regulation of alternative splicing has contributed to the evolution of complexity and diversity in biological systems.

Transmission at an identified chemical synapse between two giant molluscan neurones, in the snail Achatina fulica, was sampled continuously from late embryogenesis to adulthood. The laboratory culture and reproductive life-cycle of the snail are described. The propagation of spontaneous excitatory postsynaptic potentials (Epsps) into the postsynaptic soma was documented throughout development. Short-term facilitation (Epsp(,2)/Epsp(,1)) was present at the identified synapse at all ages studied. Over a series of 100 trials, embryonic synapse showed a net synaptic depression; while, postembryonically, there was a progressive increase in frequency-facilitation with increasing age. A quantal analysis of transmission indicates that the amplitude of the quantal unit declines in parallel with the decrease in the postsynaptic input resistance. There is a progressive (20-fold) increase in quantal content from embryos to adults. The developmental increase in transmission at the synapse is primarily presynaptic in origin. Structural correlates for the electrophysiological findings were discussed.

The 2-50 transgenic mouse is a mutant containing the functional exons of human c-myc, an oncogene and cell cycle controller, under the control of the minimal sequence of the promoter of myelin basic protein, a component of the sheath surrounding axons of neurons. The transgene complex is expressed only in oligodendrocytes during a limited period of neonatal life, and is not detectable in large amounts. The animals suffer significant loss of oligodendrocyte precursor cells prior to myelination and onset of myelin formation is delayed. These animals elaborate only an incomplete myelin sheath in the central nervous system. Quantitative genetic analysis was used to characterize the transgene insertion and optic nerves from transgenic and non-transgenic animals were used for light and election microscopy, for electrophysiological testing and for immunohistochemical studies of glial cell subpopulations and axonal cytoskeletal components.

The mammalian cerebral cortex is a remarkable product of brain evolution, and is the structure that most distinctively delineates the human species from others (Northcutt and Kaas, 1995; Rakic, 1988). Neurons in the adult brain are organised into cytoarchitectonic areas, defined by distinct biochemical, morphological and physiological characteristics (Rakic 1988). Remarkably, this complex structure is generated from a simple neuroepithelium. (For complete abstract open document)

Thesis (Ph. D.)--University of North Texas, Aug., 2007. / Title from title page display. Includes bibliographical references.