ROLE OF THE FRONTAL EYE FIELD, SUPERIOR COLLICULUS, AND BASAL GANGLIA IN FLEXIBLE SACCADE BEHAVIOR

A distributed network of cortical and subcortical brain regions mediates the control of voluntary behavior, but it is unclear how this complex system may flexibly shift between different behavioral events. This thesis describes the neurophysiological changes in several key nuclei across the brain during flexible behavior, using saccadic eye movements in rhesus macaque monkeys. We examined five nuclei critical for saccade initiation and modulation: the frontal eye field (FEF) in the cerebral cortex, the subthalamic nucleus (STN), caudate nucleus (CD), and substantia nigra pars reticulata (SNr) in the basal ganglia (BG), and the superior colliculus (SC) in the midbrain. The first study tested whether a ‘threshold’ theory of how neuronal activity cues saccade initiation is consistent with the flexible control of behavior. The theory suggests there is a fixed level of FEF and SC neuronal activation at which saccades are initiated. Our results provide strong evidence against a fixed saccade threshold in either structure during flexible behavior, and indicate that threshold variability might depend on the level of inhibitory signals applied to the FEF or SC. The next two studies investigated the BG network as a likely candidate to modulate a saccade initiation mechanism, based on strong inhibitory output signals from the BG to the FEF and SC. We investigated the STN and CD (BG input), and the SNr (BG oculomotor output) to examine changes across the BG network. This revealed robust task-contingent shifts in BG signaling (Chapter 3), which uniquely impacted saccade initiation according to behavioral condition (Chapters 3 and 4). The thesis concludes with a published short review of the mechanistic effects of BG deep brain stimulation (Chapter 5), and a general discussion including proof of concept saccade behavioral changes in an MPTP-induced Parkinsonian model (Chapter 6). The studies presented here demonstrate that the conditions for saccade initiation by the FEF and SC vary according to behavioral condition, while simultaneously, large-scale task dependent shifts occur in BG signaling consistent with the observed modulation of FEF and SC activity. Taken together, these describe a mechanistic framework by which the cortico-BG loop may contribute to the flexible control of behavior.

U, FE, AND LI ISOTOPE RATIOS IN THE MINERALIZED AND BARREN AREAS OF THE KOMBOLGIE BASIN

The Paleo- to Meso-Proterozoic Jabiluka unconformity related uranium mine is located within the Alligator River Uranium Field, found in the Northern Territories, Australia. The uranium ore is hosted in the late middle Paleoproterozoic Cahill Formation, which is unconformably overlain by a group of unmetamorphosed conglomerates known as the Kombolgie subgroup. The Kombolgie subgroup provided the source for oxidized basinal brines, carrying U as the mobile form U(VI), which interacted with reducing lithologies in the Cahill formation, thus reducing U(VI) to the solid U(IV), and leading to the precipitation of uraninite (UO2). In order to characterize fluid interaction with the ore body and compare that to areas without mineralization, several isotopic tracers were studied on a series of clay samples from drill core at Jabiluka as well as in barren areas throughout the ARUF. Among the potential tracers, three were selected: U (redox sensitive and recent fluid mobilization), Fe (redox sensitive), and Li (fractionated by hydrothermal fluids and adsorption reactions). δ238U values were found to be closely linked to the mineralogy, with samples with higher K/Al ratios (indicating high illite and low chlorite concentrations) having higher δ238U values. This demonstrates that 235U preferentially absorbs onto the surface of chlorite during hydrothermal circulation. In addition, δ234U values lie far from secular equilibrium (δ234U of 30‰), indicating there was addition or removal of 234U from the surface of the samples from recent (<2.5Ma) interactions of mobile fluids. δ57Fe values were found to be related to lithology and spatially to known uranium deposits. Decreasing δ57Fe values were found with increasing depth to the unconformity in a drill hole directly above the ore zone, but not in drill holes in the barren area. Similarly to δ238U, δ7Li is found to correlate with mineralogy, with higher δ7Li values associated with samples with more chlorite. In addition, higher δ7Li values are found at greater depth throughout the basin, indicating that the direction of the mineralizing fluid circulation was upwards from the Cahill formation to the Kombolgie subgroup.