published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Physiology / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Anatomy / Master / Master of Philosophy

Rainfall is the most important factor limiting primary production, and hence food availability, in ecosystems. This study tests the thesis that, under conditions where rainfall is unpredictable and food supply varies spatially and temporally from year-to-year, physiological energy-saving mechanisms should evolve in animals for which migration is not an option to avoid periods of low habitat productivity. Apart from the normally erratic rainfall patterns characteristic of arid regions, unpredictable seasonal rainfall may also occur in mesic zones as a consequence of climatic phenomena such as the El Niño Southern Oscillations (ENSO). Using two hypothetical models, this study attempts to determine whether the respective evolutionary history of both aridity and ENSO can be detected in the various phenotypic physiological traits of Rhabdomys pumilio from across southern Africa. Model 1 predicts that a gradient of conservatism of physiological traits related to metabolism, will be detectable along an aridity gradient. Model 2 predicts an increase in the conservatism of similar traits correlated with both the aridity gradient and the gradient of negative rainfall anomalies that are associated with the ENSO. Measurements of circadian rhythms of body temperature and oxygen consumption of individuals of R. pumilio collected from six sites across southern Africa showed that the geographic variation in the physiological traits and proximate responses of this species was explained better by Model 2 than by Model 1. Furthermore, for some traits and proximate responses of this species it was shown that, although the stresses associated with unpredictable rainfall occur less frequently in non-desert ENSO-zones, they are nevertheless sufficient to mimic the selection pressures of rainfall unpredictability in arid zones. This study also highlighted the low basal rates of metabolism and the other conservative physiological traits of this species as a whole. The basal metabolic rate of 0.819 mlO₂g/h and the minimum wet thermal conductance of 0.110 mlO₂/g/h/ºC are lower than that predicted by allometry. The circadian amplitude of body temperature of 2.52°C and the circadian amplitude of oxygen consumption of 1.39 mlO₂/g/h were higher than those predicted by allometric equations. These deviations from predicted values were attributed to the adaptedness of this species to the physiological energy stresses associated with unpredictable resource availability in southern Africa. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1998.

Differences in fatty acid distributions in adipose tissue and fatty acid synthetase levels in the liver were determined in Strain A/ST mice of different ages and diets. Since fatty acids have been found to be influential in many disease processes such as heart disease and cancer, which become more prevalent with increasing age, it is important to understand the processes of fat metabolism and changes that occur during the life-stage of senescence. Fatty acid distributions were determined by gas liquid chromatography and fatty acid synthetase (FAS) activities by spectrophotometry.The data from FAS analyses indicated that the mice fed the highfat palmitic acid and low-fat corn oil diets were similar to previous research. The mice fed the stearic acid diets had FAS activity that was affected in a very different manner than other high-fat diets.The results of this study also indicated that aging does not significantly effect the distribution of fatty acids in the adipose tissue of experimental mice. Weight gain in the middle age mice appears to be the result of an increase in all types of fatty acids and not just increased storage of one or a few types. / Department of Biology

I conducted electrophysiological work in C57BL/6J (B6) and PWD/PhJ (PWD) mice, with the goal of providing insight into the genetic and physiological controls of calcium intake. Prior behavioral preference tests indicated that PWD mice have higher preferences for calcium compounds compared to B6 mice, though several mechanisms could underlie this observation. I therefore measured taste-evoked chorda tympani (CT) responses in B6 and PWD mice, in order to investigate the specific role of taste sensation. A second experiment was conducted to investigate the role of the calciumsensing receptor (CaSR) is in gustatory transduction of calcium ions, using the CaSR agonist glutathione. In experiment 1, responses were significantly larger in PWD than B6 mice for CaCl2, MgCl2, citric acid and quinine, but did not differ between the strains for sucrose, KCl and NaCl. These strain differences in CT responses were especially large for tonic, rather than phasic, responding. These data suggest that differences in peripheral events, such as taste transduction, contribute to differences between B6 and PWD mice in preferences for taste solutions such as CaCl2. In experiment 2, glutathione at 100 μM had negligible effects on taste-evoked CT responses, which does not support a role for CaSR in mediating taste transduction of calcium ions. / Department of Physiology and Health Science

Neuromodulation allows flexibility within networks of neurons controlling rhythmic motor behaviours. This thesis explores how purinergic and cholinergic neuromodulation contributes to the functioning of spinal motor networks in mice. Purinergic modulation in the spinal cord was investigated using neonatal mouse in vitro spinal cord preparations in which locomotor-related bursts of activity were pharmacologically induced. Ventral root recordings from these preparations showed that glia release ATP, which is broken down to adenosine and binds to A1 adenosine receptors to reduce the frequency of locomotor-related bursts. Whole-cell patch-clamp recordings showed that adenosine opens leak potassium channels in ventral horn interneurons, leading to general network inhibition. Interestingly, although adenosine reduces synaptic inputs in interneurons and motoneurons, interneurons show a reversible hyperpolarisation and reduction of miniature postsynaptic currents (mPSCs) in response to adenosine, while motoneurons show a reversible depolarisation and no change in mPSCs. It was therefore concluded that adenosine opens leak potassium channels in ventral horn interneurons which reduces the speed of locomotor-related output from the whole network. However, motoneuron activity is prevented from falling so far as to cause muscle contraction to cease. Cholinergic modulation of mouse spinal motor networks was also investigated. Pitx2+ cells, known to be the source of cholinergic C-bouton inputs to motoneurons, were selectively transfected with channelrhodopsin and light was used to activate the Pitx2+ cell population. Pitx2+ cell activation was found to reduce rheobase and range of firing in small numbers of spinal motoneurons. The role of Pitx2+ cells in behaviour was also investigated by testing adult mice before and after Pitx2+ cell ablation. No difference in performance was observed in reaching or ladder walking tasks. It therefore seems likely that activation of Pitx2+ cells modulates motoneurons via C bouton synapses, but this modulation is task-dependent and is not critical for goal-directed movements requiring fine motor control.

Muscular dystrophy is a genetic disease which affects the morphology, physiology and biochemical nature of the muscle fiber. This study was designed to examine the progressive effects of muscular dystrophy on the differentiation process of skeletal muscle. Chapter 1 examines the neonatal development of muscle spindles and their intrafusal fibers in the soleus and extensor digitorum longus (EDL) of genetically dystrophic mice according to histochemical, quantitative, and ultrastructural parameters. Despite alterations in the surrounding extrafusal fibers, muscle spindles and their intrafusal fibers appeared enzymatically and histologically unaffected in incipient stages of murine dystrophy. In the second chapter the distribution and concentration of parvalbumin (PV), a calcium-binding protein, in 32 and 2-week-old dystrophic mice was mapped by immunohistochemical and biochemical procedures. The number of parvalbumin-immunoreactive fibers was significantly reduced in the adult dystrophic EDL but slightly increased in the adult dystrophic soleus. No differences between strains were observed in the 2-week samples. These findings were supported by routine myosin ATPase histochemistry. Parvalbumin was isolated on SDS-PAGE gels and the concentration of PV was estimated by a RIA. These results confirmed the immunohistochemical data in that PV content was dramatically reduced in the adult dystrophic EDL and significantly increased in the dystrophic soleus. No changes were detected in the samples of the 2-week-old muscles. The similarity in the distribution and content of PV between the fast and slow dystrophic muscles at 32 weeks of age suggests an alteration in the distribution and phenotypic expression of fiber types in muscular dystrophy and supports the hypothesis that dystrophy alters the normal differentiation process of skeletal muscle. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

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