The goal of this research project is to provide a better understanding of the anatomy and physiology of neurons responsible for oculomotor behavior by taking advantage of the unique genetic and developmental features of the zebrafish model system. The structural blueprint responsible for eye movements derives from highly conserved genetic and anatomical profiles specific to each of the 8 embryonic hindbrain compartments. A multidisciplinary approach will focus on the central processing of visual and vestibular sensory signals in three distinct brainstem nuclei, each performing a unique integrative role in oculomotor behavior and representing a separate genetic/rhombomeric (rh) origin. Two nuclei that convert head angular acceleration and other velocity-related inputs to horizontal eye velocity and eye position related signals are located in rh 7 and 8 respectively. The third nucleus, located in rh 5 orients the eyes in a manner compensatory for head tilt. Genetic and fluorescent reporters will be used to visualize these neurons allowing direct analysis of single cell morphology and physiology during the formation of each specific eye movement-related network. Since cell laser perturbations along with structural and behavioral analysis of single gene mutations will distinguish novel roles for particular neurons and genes in the assembly and function of these oculomotor networks.
Aim 1 will study normal ontogeny, physiology and behavior during formation of operational neural circuits using transgenic GFP markers.
Aim 2 will investigate neuronal and network dynamics in larval and juvenile stages using single cell laser photochemical uncaging/ablation and altered visual experience.
Aim 3 will manipulate the expression of Hox paralog group 3 and 4 genes to alter genetic and developmental properties underlying neuronal and network specificity as well as analyze adult viable and embryonic-lethal mutations.
Aim 4 will screen for the role of single genes in the development and function of dentified neurons and proto-networks. This project will utilize contemporary electrophysiological, computational and genetic approaches in conjunction with non-invasive two photon laser scanning microscopy to identify genes essential for oculomotor signal processing in vertebrates.
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