published_or_final_version / abstract / Physiology / Doctoral / Doctor of Philosophy

Thesis (M.S.)--University of British Columbia, 2007. / Includes bibliographical references (leaves 35-40). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--University of British Columbia, 2007. / Includes bibliographical references (leaves 35-40).

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

This study re-examines the morphological data and conclusions of Spoor, Wood, and Zonneveld concerning the morphology of the vestibular apparatus in relation to locomotor behavior in hominids (1994). The pedal and labyrinthine morphology of early hominid taxa are functionally analyzed for classification as either obligate bipeds or habitual bipeds with primarily arboreal locomotion. The bony labyrinth is investigated since the anatomy of the semicircular canals of the vestibular auditory system can be determined in fossil crania through computed tomographical analysis. It is thought that a relationship exists between semicircular canal size and locomotor behavior. Functionally modern pedal morphology precedes modern vestibular morphology in the fossil record. Complete modern pedal morphology, however, appears concurrently with modern vestibular morphology first at Homo erectus. A comparison of the genes involved in the development of both pedal and labyrinthine morphology was undertaken. It was found that only fibroblast growth factor 8 (FgfS) and sonic hedgehog (Shh) are shared between these systems in the determination of positional information. It is found that the function of Fgf8 in otic induction and in limb bud formation is very different. It is also found that the function of Shh in vestibular and pedal morphogenesis is different. Therefore, it is unlikely for alteration in the function or in the expression of either gene to result in the observed differences in pedal and vestibular morphology between early hominid taxa: Australopithecus afarensis, Australopithecus africanus, Homo habilis; and Homo erectus. My examination of the data on the timing of changes in pedal morphology rejects Spoor, Wood, and Zonneveld's conclusion. Moreover I find no gene mutation which could account for simultaneous change in the shape of the semicircular canals and the proportions of the metatarsals and pedal phalanges. Instead, it is postulated that the change to modern vestibular morphology at Homo erectus is in response to a concurrent enlargement in cranial capacity. It is also postulated that persistence of panid vestibular morphology in the semicircular canals of hominid taxa: Australopithecus afarensis, Australopithecus africanus, and Homo habilis is a functionally neutral trait in regard to bipedal locomotor capability. / Department of Anthropology

Psychiatric disorders and cognitive impairment are increasingly being described in patients with vestibular pathology. Yet frameworks that describe the link between emotion, memory and the vestibular system have yet to reach maturity, partly because studies have not yet provided detailed accounts of behavioral changes in experimental animals, or in man. One of the goals of this thesis was to use experimental psychology to define changes in memory and emotional behaviour in rats given bilateral vestibular deafferentation (BVD, n=18) or sham surgery (Sham, n=17). In an elevated-plus maze task, BVD rats made up to 166% greater open arm entries and spent up to 42% more time in the open arms compared to Sham rats. In an elevated-T maze task, BVD rats failed to develop a normal learned inhibition response to open space. In an open field maze BVD rats consistently showed 50-60% greater movement velocity, spent on average 35% more time in the inner most aversive part of the arena, and failed to show the normal boundary-seeking behaviour (thigmotaxis) typical of untreated or Sham rats. In a social interaction test BVD rats spent up to 34% less time engaged in social contact compared to Sham rats. In a hyponeophagia test, BVD rats� latency to eat was 70% greater than Sham rats at 3-weeks post-op., however this difference disappeared at 3- and 5-months. These findings suggest that BVD treatment may in some cases disrupt normal behavioral inhibition. Memory performance was also affected. In a T-maze task BVD rats achieved 40-60% correct arm entries, compared to 90-100% for Sham controls. In a foraging task carried out in darkness, BVD rats� initial homing angle was random, homing paths were ~70% longer, and reference memory errors were ~56% greater compared to Sham rats. To elucidate possible neurochemical substrates for these behavioral changes, western blot assays on monoamine proteins were carried out on tissue from a naïve set of rats (BVD n=6; Sham n=6). In BVD rats, serotonin transporter protein expression was 39% lower in CA1 hippocampus and 27% lower in the forebrain region, despite forebrain tryptophan hydroxylase expression being 34% upregulated. Tyrosine hydroxylase expression in the forebrain region was 27% lower in BVD rats. Proteins related to synaptogenesis were also investigated. In the dentate gyrus SNAP-25 was 37% upregulated in BVD rats, while in area CA2/3 of the hippocampus neurofilament-L was 13% upregulated. Forebrain and entorhinal cortex drebrin expression was 28% and 38% downregulated in BVD rats. Neurofilament-L was also 31% downregulated in the forebrain region of BVD rats. To test whether any of these behavioral or biochemical changes may have been attributable to chronic physiological stress, a corticosterone assay was carried out at the conclusion of behavioral testing; however, the no significant between treatment differences were found. In conclusion, vestibular information appears to be needed for the acquisition of spatial and reference memory as well as the normal expression of emotional behaviour. The neurochemical changes described herein point toward possible substrates for these behaviors, however their full significance has yet to be determined.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Psychiatric disorders and cognitive impairment are increasingly being described in patients with vestibular pathology. Yet frameworks that describe the link between emotion, memory and the vestibular system have yet to reach maturity, partly because studies have not yet provided detailed accounts of behavioral changes in experimental animals, or in man. One of the goals of this thesis was to use experimental psychology to define changes in memory and emotional behaviour in rats given bilateral vestibular deafferentation (BVD, n=18) or sham surgery (Sham, n=17). In an elevated-plus maze task, BVD rats made up to 166% greater open arm entries and spent up to 42% more time in the open arms compared to Sham rats. In an elevated-T maze task, BVD rats failed to develop a normal learned inhibition response to open space. In an open field maze BVD rats consistently showed 50-60% greater movement velocity, spent on average 35% more time in the inner most aversive part of the arena, and failed to show the normal boundary-seeking behaviour (thigmotaxis) typical of untreated or Sham rats. In a social interaction test BVD rats spent up to 34% less time engaged in social contact compared to Sham rats. In a hyponeophagia test, BVD rats� latency to eat was 70% greater than Sham rats at 3-weeks post-op., however this difference disappeared at 3- and 5-months. These findings suggest that BVD treatment may in some cases disrupt normal behavioral inhibition. Memory performance was also affected. In a T-maze task BVD rats achieved 40-60% correct arm entries, compared to 90-100% for Sham controls. In a foraging task carried out in darkness, BVD rats� initial homing angle was random, homing paths were ~70% longer, and reference memory errors were ~56% greater compared to Sham rats. To elucidate possible neurochemical substrates for these behavioral changes, western blot assays on monoamine proteins were carried out on tissue from a naïve set of rats (BVD n=6; Sham n=6). In BVD rats, serotonin transporter protein expression was 39% lower in CA1 hippocampus and 27% lower in the forebrain region, despite forebrain tryptophan hydroxylase expression being 34% upregulated. Tyrosine hydroxylase expression in the forebrain region was 27% lower in BVD rats. Proteins related to synaptogenesis were also investigated. In the dentate gyrus SNAP-25 was 37% upregulated in BVD rats, while in area CA2/3 of the hippocampus neurofilament-L was 13% upregulated. Forebrain and entorhinal cortex drebrin expression was 28% and 38% downregulated in BVD rats. Neurofilament-L was also 31% downregulated in the forebrain region of BVD rats. To test whether any of these behavioral or biochemical changes may have been attributable to chronic physiological stress, a corticosterone assay was carried out at the conclusion of behavioral testing; however, the no significant between treatment differences were found. In conclusion, vestibular information appears to be needed for the acquisition of spatial and reference memory as well as the normal expression of emotional behaviour. The neurochemical changes described herein point toward possible substrates for these behaviors, however their full significance has yet to be determined.

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.

No description available.