The goal of this research project is to provide a better understanding of the control of eye movements by integrating the known physiology and anatomy of neurons in the goldfish with the developmental and molecular potential of the zebrafish model system. The structural blueprint responsible for all oculomotor behaviors appears to be the result of highly conserved genetic and anatomical profiles that create 8 embryonic hindbrain compartments. It is hypothesized that single genes essential for the development and function of specific eye movement-related neurons and circuits can be analyzed by measurement of oculomotor behavior in zebrafish larvae and mutants. The central processing of visual and vestibular sensory signals that produce horizontal eye movements depends on two brainstem nuclei referred to as neural integrators since they convert either head acceleration or velocity-related inputs to eye velocity and eye position-related signals. In conjunction with cerebellar processing, these signals are necessary for oculomotor performance and learning. Strikingly, there appear to be only two precerebellar pathways uniquely related to horizontal oculomotor behavior in the goldfish. These comprise the eye velocity nucleus that forms the mossy fiber pathway and the inferior olive that forms the climbing fiber pathway to Purkinje cells that directly control specific subgroups of vestibuloocular neurons. This project will utilize contemporary computational and electrophysiological approaches to parse out the contributions of intrinsic 'cellular' versus extrinsic 'network' signal processing capabilities of these two precerebellar pathways by employing multiple intra- and extracellular recording in goldfish and noninvasive confocal and two photon laser scanning microscopy in zebrafish. A second set of aims will focus on the morphology and genetic analysis of the above mentioned subgroups in embryonic zebrafish thereby allowing structural and behavioral analysis of relevant single gene mutations. The long term goal of the research project will be to characterize candidate genetic pathways that are essential for defining the operation of neurons and circuits responsible for horizontal oculomotor signal processing and motor learning.
| Choi, Soonwook; Yu, Eunah; Hwang, Eunjin et al. (2016) Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain. Proc Natl Acad Sci U S A 113:2270-5 |
| Choi, Soonwook; Yu, Eunah; Lee, Seongwon et al. (2015) Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness. Proc Natl Acad Sci U S A 112:7839-44 |
| Hensbroek, Robert A; Ruigrok, Tom J H; van Beugen, Boeke J et al. (2015) Visuo-vestibular information processing by unipolar brush cells in the rabbit flocculus. Cerebellum 14:578-83 |
| Winkelman, Beerend H J; Belton, Tim; Suh, Minah et al. (2014) Nonvisual complex spike signals in the rabbit cerebellar flocculus. J Neurosci 34:3218-30 |
| Hensbroek, Robert A; Belton, Tim; van Beugen, Boeke J et al. (2014) Identifying Purkinje cells using only their spontaneous simple spike activity. J Neurosci Methods 232:173-80 |
| Ivannikov, Maxim V; Sugimori, Mutsuyuki; Llinás, Rodolfo R (2013) Synaptic vesicle exocytosis in hippocampal synaptosomes correlates directly with total mitochondrial volume. J Mol Neurosci 49:223-30 |
| Chagnaud, Boris P; Zee, Michele C; Baker, Robert et al. (2012) Innovations in motoneuron synchrony drive rapid temporal modulations in vertebrate acoustic signaling. J Neurophysiol 107:3528-42 |
| Chagnaud, Boris P; Baker, Robert; Bass, Andrew H (2011) Vocalization frequency and duration are coded in separate hindbrain nuclei. Nat Commun 2:346 |
| Simpson, John I (2011) Crossing zones in the vestibulocerebellum: a commentary. Cerebellum 10:515-22 |
| Park, Young-Gyun; Park, Hye-Yeon; Lee, C Justin et al. (2010) Ca(V)3.1 is a tremor rhythm pacemaker in the inferior olive. Proc Natl Acad Sci U S A 107:10731-6 |
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