In most organisms the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). Zebrafish embryos can also arrest development (suspended animation) to tolerate low oxygen. I tested the hypothesis that induction of HIF-1 and associated target genes (eg. erythropoietin) during embryonic development would alter the hypoxia tolerance phenotype of larval and adult fish. I exposed zebrafish embryos at 3 developmental stages to acute (4 h) bouts of hypoxia (5% dissolved oxygen, DO) or anoxia (<0.5% DO). I found that embryos that mount a HIF-1 response have a greater hypoxia tolerance as larvae. Additionally, populations that experienced embryonic HIF-1 induction show an increase in the proportion of males (~70% male), that are more hypoxia tolerant than female fish, compared to control populations (~45% male). Overall, induction of HIF-1 during ontogeny alters the larval and adult zebrafish phenotype to better tolerate future hypoxic bouts. / NSERC

Sympathetic catecholamines and co-transmitters released within the gastrointestinal (GI) tract provide dynamic regulation of gut motility, fluid secretion, blood flow and immune cell function. Pathological GI inflammation in patients with inflammatory bowel diseases (IBD) evokes functional and structural plasticity in sympathetic neurons that innervate the gut, which may contribute to symptom generation. The mechanisms responsible for aberrant sympathetic behaviour during colonic inflammation remain elusive, though evidence points to a role for mediators of the mucosal immune response. Interleukin (IL)-17 is the principal cytokine of the novel TH17 lineage of helper T cells. Based on mounting clinical, genetic and experimental evidence, IL-17 is thought to play a pivotal role in the immunopathogenesis of IBD. However, nothing is known of the contribution of IL-17 to sympathetic neuroplasticity during chronic inflammatory disease. We hypothesized that remodelling of postganglionic sympathetic axons occurs in response to exposure of axons to the inflamed colonic milieu and that IL-17 serves as the primary mediator of this neuroanatomical remodelling. An increase in tyrosine hydroxylase (TH) immunoreactivity, a marker of sympathetic axons, was observed in the muscularis externae and mucosae of colons from mice subjected to acute and chronic models of dextran sulphate sodium (DSS)-induced colitis. In parallel, we found markedly elevated levels of IL-17 in the serum and colonic tissues of mice with colitis. To investigate whether the colitis microenvironment promoted axonal growth, distal neurites of adult sympathetic neurons from the superior mesenteric ganglion (SMG) were incubated in supernatant collected from explant cultures of inflamed colon. Colitis supernatant enhanced neurite outgrowth from gut-projecting SMG neurons compared to supernatants from control colon. Importantly, this effect was abrogated following the addition of IL-17-neutralising antiserum to cultures. Moreover, IL-17 increased the morphological complexity of SMG neurites in vitro while none of the other inflammatory cytokines known to be elevated during IBD had a similar effect. These findings suggest a novel role for IL-17 as a mediator of sympathetic neuroanatomical plasticity during colonic inflammation. Whether this contributes to the functional deficits and chronic inflammatory response that occurs in the GI tract during IBD remains to be determined. / Thesis (Master, Physiology) -- Queen's University, 2011-08-10 09:40:13.514

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No description available.

Long term memory (LTM) formation is a complex process involving signalling cascades, new protein synthesis and gene regulation. Increasing evidence demonstrates a role of intrinsic plasticity in memory formation, but the underlying molecular mechanisms remain relatively unknown. LTM was established using an aversive operant conditioning model in Lymnaea stagnalis. Using intracellular electrophysiology in an isolated preparation, increased gain of firing frequency was observed in the RPeD1 neuron after LTM. This provides the first demonstration of intrinsic plasticity after operant conditioning in RPeD1, a neuron required for the conditioned behaviour and LTM. I also determined the contribution of the transcription factor men1 to plasticity. Using in vivo RNAi silencing, I found that men1 is required for LTM and increasing RPeD1 excitability during consolidation, demonstrating men1-mediated intrinsic plasticity is critical for LTM. I propose a new model of memory formation in which men1-dependent increase of excitability during consolidation is required for LTM.

Long term memory (LTM) formation is a complex process involving signalling cascades, new protein synthesis and gene regulation. Increasing evidence demonstrates a role of intrinsic plasticity in memory formation, but the underlying molecular mechanisms remain relatively unknown. LTM was established using an aversive operant conditioning model in Lymnaea stagnalis. Using intracellular electrophysiology in an isolated preparation, increased gain of firing frequency was observed in the RPeD1 neuron after LTM. This provides the first demonstration of intrinsic plasticity after operant conditioning in RPeD1, a neuron required for the conditioned behaviour and LTM. I also determined the contribution of the transcription factor men1 to plasticity. Using in vivo RNAi silencing, I found that men1 is required for LTM and increasing RPeD1 excitability during consolidation, demonstrating men1-mediated intrinsic plasticity is critical for LTM. I propose a new model of memory formation in which men1-dependent increase of excitability during consolidation is required for LTM.

No description available.

No description available.

Sexual dimorphism in life history traits may influence the distribution of the sexes,population sex ratios, the maintenance of sex in populations, and the evolutionarypotential of a species. In bryophytes, sexual dimorphism in traits related to growth andreproduction may be responsible for female-biased population sex ratios and a lack ofsexual reproduction. I examined the roles of natural selection in maintaining sexualdimorphism in the context of impacts on bryophyte population sex ratios, usingMarchantia inflexa as a model system. My studies included an assessment of amongpopulationvariation in habitat use by the sexes, comparison of phenotypes betweensingle-sex and both-sex populations, a field study of natural selection, and a comparisonof the influence of selection on asexual and sexual fitness components.The sexes of M. inflexa were sexually dimorphic in investment in growth, asexualand sexual reproduction. The sexes were spatially separated in populations, but thesexes overlapped in habitat use. Populations differed in growth, asexual reproductionrates, degrees of sexual dimorphism, and strength of among-trait correlations. Plantsfrom single-sex and both-sex populations differed in investment in growth and asexualreproduction, but the two population types showed the same degree of sexualdimorphism. Thus, local environment may be more influential than the presence of theopposite sex in maintaining sexual dimorphism.Selection on sexually dimorphic traits was both sex-specific and environmentallydependent. Between-sex correlations were not significant in the greenhouse but weresignificant in the field thus, evolution and expression of sexual dimorphism in nature maybe constrained by among-trait and between-sex correlations. Additionally, femalesincurred a cost of plasticity that males did not. Because there was a negative trade-offbetween sexual and asexual fitness, overall lifetime selection may result in a differentpicture of how the sexes experience selection. The combination of sex-specific andenvironment-dependent selection, and sex-specific costs to plasticity may not onlymaintain sexually dimorphic traits but also ensure the persistence of both sexes in apopulation.

The brain undergoes structural changes in response to new experiences like learning a new skill. Skilled motor movements depend greatly on the primary motor cortex for their execution. Recent studies describe rat strain differences in motor performance related to differential synaptic efficacy in the motor cortex of rats. Previous studies identified differences in motor performance related to differential dendritic morphology and strain related differences in synaptic function in the motor cortex. Strain differences are one way of investigating anatomical organization and behaviour of the motor system. The object of this research was to examine strain related differences in dendritic morphology in layer II / III pyramidal cells of the forelimb area of the sensory motor cortex in both Long-Evans and Fischer 344 rats after reach training. This research also examined whether changes in reaching behaviour could be attributed to changes in dendritic morphology. Rats were trained once a day for 30 days to reach for a food pellet through a slot in a reaching box. Pyramidal cells in the motor sensory forelimb (MSF) cortex were stained with the Golgi Cox method. Subsequent analysis of Sholl and branch order data of cell drawings determined that there were no significant differences in any measure of dendritic length or dendritic length at branch order 3, 4, 5 of pyramidal cells in layer II/III of the MSF cortex between the Long Evans and Fischer 344 rat strain. The only significant strain related difference was that the Fischer 344 strain exhibited fewer reaches for each food pellet obtained, demonstrating greater reaching proficiency than similarly trained Long-Evans rats. These findings suggest that further research examining strain comparisons is required to understand the neural mechanisms underlying the differences in motor behaviour observed in these rat strains.