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.
|Ma, Leung-Hang; Grove, Charlotte L; Baker, Robert (2014) Development of oculomotor circuitry independent of hox3 genes. Nat Commun 5:4221|
|Straka, Hans; Baker, Robert (2013) Vestibular blueprint in early vertebrates. Front Neural Circuits 7:182|
|Bianco, Isaac H; Ma, Leung-Hang; Schoppik, David et al. (2012) The tangential nucleus controls a gravito-inertial vestibulo-ocular reflex. Curr Biol 22:1285-95|
|Lyons, Peter J; Ma, Leung-hang; Baker, Robert et al. (2010) Carboxypeptidase A6 in zebrafish development and implications for VIth cranial nerve pathfinding. PLoS One 5:e12967|
|Ma, Leung-Hang; Punnamoottil, Beena; Rinkwitz, Silke et al. (2009) Mosaic hoxb4a neuronal pleiotropism in zebrafish caudal hindbrain. PLoS One 4:e5944|
|Lambert, Francois M; Beck, James C; Baker, Robert et al. (2008) Semicircular canal size determines the developmental onset of angular vestibuloocular reflexes in larval Xenopus. J Neurosci 28:8086-95|
|Straka, H; Baker, R; Gilland, E (2001) Rhombomeric organization of vestibular pathways in larval frogs. J Comp Neurol 437:42-55|
|Graf, W; Spencer, R; Baker, H et al. (2001) Vestibuloocular reflex of the adult flatfish. III. A species-specific reciprocal pattern of excitation and inhibition. J Neurophysiol 86:1376-88|
|Nguyen, L T; Spencer, R F (1999) Abducens internuclear and ascending tract of Deiters inputs to medial rectus motoneurons in the cat oculomotor nucleus: neurotransmitters. J Comp Neurol 411:73-86|
|Nguyen, L T; Baker, R; Spencer, R F (1999) Abducens internuclear and ascending tract of deiters inputs to medial rectus motoneurons in the cat oculomotor nucleus: synaptic organization. J Comp Neurol 405:141-59|
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