Thesis (M.S.)--Ohio University, August, 2006. / Title from PDF t.p. Includes bibliographical references.

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references. Also available in electronic version. Access restricted to campus users.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 115-123). Also available in electronic version.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2005. / Includes bibliographical references (leaves 136-146). Also available in electronic version.

This thesis describes the design, synthesis and development of fluorescent probes to monitor synaptic transmission at individual presynaptic terminals in the mouse brain. Two distinct approaches to accomplish this are discussed. The first approach seeks to monitor synaptic activity by using pH-sensitive endocytic membrane probes to label active presynaptic terminals. The second approach seeks to monitor synaptic activity by loading small fluorescent molecules into presynaptic vesicles and studying their evoked release upon stimulation. The first chapter of this thesis describes currently available techniques that are used to study synaptic transmission in the brain. The use of electrochemical techniques is discussed and the use of fluorescent reporters is introduced as a means to image single synapses with high resolution. Chapter II of this thesis describes the rational design of pH-sensitive membrane probes for labeling recycling vesicles. The synthesis, photophysical properties and biological characterization of these probes are described. Although these probes proved to be too lipophilic to work well in the brain tissue and neuronal culture, their use on the cell surface is demonstrated. Furthermore, the structure activity relationship established by this library of probes can be used to direct the future development of pH-sensing endocytic dyes. Chapter III and IV of this thesis describe the development of new generations of Fluorescent False Neurotransmitters (FFNs) for imaging vesicular content release from individual presynaptic terminals in the brain. Chapter III introduces a novel imaging agent, FFN200, for monitoring and quantifying dopamine release from individual synaptic terminals in the mouse brain. Chapter IV describes the exploration and screening of small fluorescent molecules in the mouse brain for the purpose of developing FFNs at synaptic terminals other than dopamine. FFN7122 is introduced as the first FFN to be developed for terminals outside of dopamine. FFN7122 is shown to be a marker for glutamatergic terminals in the hippocampus, dorsal striatum, and motor cortex of the mouse brain. The evoked release of this probe from presynaptic vesicles is demonstrated and two hypotheses for its uptake mechanism are proposed.

Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007. / Includes bibliographical references (leaves 119-134). Also available in electronic version.

Thesis (Ph. D.)--University of California, San Diego and San Diego State University, 2003. / Vita. Includes bibliographical references.

Thesis (M.A.)--University of North Carolina Wilmington, 2008. / Title from PDF title page (October 20, 2008) Includes bibliographical references (59-71)

Background: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals change in differing conditions of light. EAATs in neurons quickly transport glutamate from the synaptic cleft, and also elicit large thermodynamically uncoupled Cl- currents when activated. We recorded synaptic EAAT currents from cones to study glutamate-uptake events elicited by glutamate release from the local cone, and from adjacent photoreceptors. We find that cones are synaptically connected via EAATs in dark ; this synaptic connection is diminished in light-adapted cones. Methods: Whole-cell patch-clamp was performed on dark- and transiently light-adapted tiger salamander cones. Endogenous EAAT currents were recorded in cones with a short depolarization to -10mV/2ms, while spontaneous transporter currents from network cones were observed while a local cone holding at -70mV constantly. DHKA, a specific transporter inhibitor, was used to identify EAAT2 currents in the cone terminals, while TBOA identified other EAAT subtypes. GABAergic and glycinergic network inputs were always blocked with picrotoxin and strychnine. Results: Spontaneous EAAT currents were observed in cones held constantly at -70mV in dark, indicating that the cones received glutamate inputs from adjacent photoreceptors. These spontaneous EAAT currents disappeared in presence of a strong light, possibly because the light suppressed glutamate releases from the adjacent photoreceptors. The spontaneous EAAT currents were blocked with TBOA, but not DHKA, an inhibitor for EAAT2 subtype, suggesting that a / non-EAAT 2 subtype may reside in a basal or perisynaptic area of cones, with a specialized ability to bind exocytosed glutamate from adjacent cones in dark. Furthermore, these results could be artificially replicated by dual-electrode recordings from two adjacent cones. When glutamate release was elicited from one cone, the TBOA-sensitive EAAT currents were observed from the other cone. Conclusions: Cones appear to act like a meshwork, synaptically connected via glutamate transporters. Light attenuates glutamate release and diminishes the cone-cone synaptic connections. This process may act as an important network mechanism for cone light adaptation. / by Matthew JM Rowan. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

The purpose of this dissertation was to gain insight into spinal sensory regulation during locomotion. To this end, I developed a novel in vitro spinal cord-hindlimb preparation (SCHP) composed of the isolated in vitro neonatal rat spinal cord oriented dorsal-up with intact hindlimbs locomoting on a custom-built treadmill or instrumented force platforms. The SCHP combines the neural and pharmacological accessibility of classic in vitro spinal cord preparations with intact sensory feedback from physiological hindlimb movements. thereby expanding our ability to study spinal sensory function. I then validated the efficacy of the SCHP for studying behaviorally-relevant, sensory-modulated locomotion by showing the impact of sensory feedback on in vitro locomotion. When locomotion was activated by serotonin and N-methyl D-aspartate, the SCHP produced kinematics and muscle activation patterns similar to the intact rat. The mechanosensory environment could significantly alter SCHP kinematics and muscle activitation patterns, showing that sensory feedback regulates in vitro spinal function. I further demonstrated that sensory feedback could reinforce or initiate SCHP locomotion. Using the SCHP custom-designed force platform system, I then investigated how presynaptic inhibition dynamically regulates sensory feedback during locomotion and how hindlimb mechanics influence this regulation. I hypothesized that contralateral limb mechanics would modulate presynaptic inhibition on the ipsilateral limb. My results indicate that contralateral limb stance-phase loading regulates ipsilateral swing-phase sensory inflow. As contralateral stance-phase force increases, contralateral afferents act via a GABAergic pathway to increase ipsilateral presynaptic inhibition, thereby inhibiting sensory feedback entering the spinal cord. Such force-sensitive contralateral presynaptic inhibition may help preserve swing, coordinate the limbs during locomotion, and adjust the sensorimotor strategy for task-specific demands. This work has important implications for sensorimotor rehabilitation. After spinal cord injury, sensory feedback is one of the few remaining inputs available for accessing spinal locomotor circuitry. Therefore, understanding how sensory feedback regulates and reinforces spinally-generated locomotion is vital for designing effective rehabilitation strategies. Further, sensory regulation is degraded by many neural insults, including spinal cord injury, Parkinson's disease, and stroke, resulting in spasticity and impaired locomotor function. This work suggests that contralateral limb loading may be an important variable for restoring appropriate sensory regulation during locomotion.