Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 262-280). Also available in print.

Dissertation (Ph.D.)--University of Toledo, 2009. / "Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Sciences." Title from title page of PDF document. Table of contents (p. iv) gives incorrect starting page numbers for "Bibliography" and "Abstract". "Bibliography" starts on p. 120 (not p. 119); "Abstract" starts on p. 150. Bibliography: p. 64-70, 97-100, 120-149.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references. Available also from UMI/Dissertation Abstracts International.

Thesis (Ph. D.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 262-280). Also available online.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 145-158).

Principal neurons of the medial superior olive (MSO) encode low-frequency sound localization cues by comparing the relative arrival time of sound to the two ears. In mammals, MSO neurons display biophysical specializations, such as voltage-gated sodium (Na[subscript v]) and potassium (K[subscript v]) channels that enable them to detect these cues with microsecond precision. In this dissertation electrophysiological techniques were used to examine the specific channel properties and functional role these channels play in MSO neurons following hearing onset. In addition, computational models that incorporated these physiological data were used to further study how the specific properties of these channels facilitate MSO function. Experiments in this dissertation showed that Na[subscript v] channels are heavily expressed in the persisomatic region of MSO neurons, but unlike those expressed in other neurons they minimally contribute to action potential generation. This is likely due to the low percentage of channels available for activation at the resting membrane potential. Current clamp recordings determined that Na[subscript v] channels counterbalance K[subscript v] channels voltage rectification by boosting near action potential threshold excitatory post-synaptic potentials (EPSPs). Further, computational modeling revealed that synaptic inputs are larger at the soma with Na[subscript v] channels restricted to the soma than when they are evenly distributed throughout the soma and dendrites. During the first few weeks after hearing onset current clamp experiments showed EPSP duration decreased while the temporal resolution for detecting the arrival time of synaptic inputs increased. These changes in EPSP duration are due in part to both the development of faster membrane response properties and increases in the expression of low voltage-activated K[subscript v] channels (K[subscript LVA]). Further investigation determined these channels display a somatically enriched distribution and act to counterbalance the distortions that result from dendritic cable filtering. This is accomplished by K[subscript LVA] actively decreasing the duration of EPSPs in a voltage dependent manner. Computational modeling confirmed these results as well as illustrating their effects on the integration of mono- versus bilateral excitation. Together these findings indicate that the expression of specialized Na[subscript v] and K[subscript v] channels facilitate the neuron’s computational task, detecting and comparing the relative timing of synaptic inputs used in low frequency sound localization. / text

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Synaptic dysfunction is a critical neuropathological feature prior to the formation of extracellular senile plaques and intracellular fibrillary tangles (NFTs) in Alzheimer’s disease (AD). The synapse loss and neurites impairment lead to synaptic dysfunction that can be induced by oligomeric Aβ. The administration of oligomeric Aβ reduced the pre-synaptic vesicle proteins and altered the cytoskeletal proteins. The synaptic vesicles (SVs) playing a crucial role to transport and recycle the SV proteins and neurotransmitters (NTs) in synaptic terminals. However, the uptake and release capabilities of SVs were also disrupted by oligomeric Aβ. The disruption of SVs recycling and neurites impairment attenuate neurotransmission that exacerbates the pathogenesis of AD. Therefore, any agents can maintain the SVs recycling and protect the neurites development that could be a therapeutic target for AD. Testosterone is a male sex steroid hormone, which is a potent therapeutic drug for neurodegenerative diseases. It has been found the neuroprotective effects for neuronal death, but the implication on synaptoprotection is still not clear. This study investigated the neuroprotective effects of testosterone from oligomeric Aβ-induced synaptic dysfunction in primary cultured hippocampal neurons. My study demonstrated that testosterone prevented Aβ-induced reduction of pre-synaptic proteins and shortening neurites. Also, testosterone could protect SVs recycling by increasing SVs unloading capability via estrogenic independent pathway. The findings reinforce the neuroprotective effects of testosterone. They are probably facilitating future development for using the concept of male sex hormone as therapy and the intervention of therapeutic drugs for AD patients. / published_or_final_version / Anatomy / Master / Master of Medical Sciences

In rats, the subnuclei of the inferior olive (IO) and thalamus exist topographic spatial representation to sinusoidal horizontal linear translations along either the antero-posterior or interaural direction. To examine the effect of GABAergic neurotransmission within the vestibular nucleus on the establishment of gravity-related topographic spatial representation in relay station of the central vestibular pathway, GABAA receptor antagonist bicuculline was used to chronically perturb GABA transmission within the vestibular nucleus of postnatal rats. Implantation of bicuculline-loaded or saline-loaded Elvax slice onto the dorsal surface of vestibular nucleus was performed in P1 rats which were allowed to recover into adulthood. Fos protein expression was used as an indicator to identify central neurons responsive to horizontal linear accelerations. In stationary or labyrinthectomized rats, Fos-immunoreactive (ir) neurons were either absent or sporadically scattered throughout the IO and thalamic subnuclei, indicating that the Fos expression in these neural area was otolithic in origin. In the saline control group, Fos expression induced by horizontal antero-posterior linear acceleration was observed in both the IO and thalamus. Responsive IO subnuclei include β subnucleus of IO and dorsomedial cell column while those in the thalamus include central medial nucleus, paracentral nucleus, mediodorsal nucleus, central lateral nucleus, zona incerta and subparafascicular nucleus of thalamus. For-ir neurons responsive to horizontal interaural linear acceleration were found in those IO subnuclei and thalamic subnuclei. When compared with the saline-treated group, the number of Fos-ir IO neurons responsive to horizontal linear acceleration was significantly lower in adult rats perturbed with bicuculline at P1. Besides, the pattern of Fos expression in both the IO and thalamus was altered in adult rats pretreated with bicuculline. In the utricle-related thalamic subnuclei, the postnatal time when Fos-ir neurons were found triggered by otolithic stimulation was delayed and the number of these Fos-ir neurons was fewer in the bicuculline-treated group than those in the saline-treated group. To investigate whether there exists a critical period for postnatal establishment of topographic spatial representation in the IO and thalamus, implantation of bicuculline-loaded Elvax slice onto the vestibular nucleus was carried out in P14 rats. The topographic spatial representation in IO and thalamus of those rats were unchanged as compared with adult rats pretreated with saline at P14. These results indicate that the GABAergic neuronal circuit in the vestibular nucleus plays an important role in postnatal establishment of topographic spatial representation in the central vestibular system. Most importantly, we documented the occurrence of a postnatal critical period (between P1 and P14) during which GABAergic transmission regulated the formation of a gravity-related spatial framework in the brain. / published_or_final_version / Physiology / Master / Master of Philosophy