The long term goal is to understand the mechanisms by which chick spinal cord motoneurons form behaviorally appropriate circuits during neural development. Such basic mechanisms play a role in nerve and spinal cord regeneration, and in plastic changes of the nervous system in response to injury. The studies are also relevant to developmental defects of both nerve and muscle. Embryonic surgery and vital staining of identified neurons with fluorescent probes will allow the dynamic behavior of the migratory muscle precursor cells and neuronal growth cones to be documented in cultured slice preparations using time lapse cinematography and video-microscopy. The molecular nature of factors that affect patterned neuronal outgrowth will be assessed by the application of poly and monoclonal antibodies to such slice preparation (i.e. antibodies to NCAM, laminin, etc.). Both polyclonal and monoclonal antibodies will be generated to limb and spinal cord at the stages of initial axonal outgrowth, in an effort to obtain antibodies that block specific growth cone decisions. Finally, the glycogen depletion technique will be used to probe the role of motoneuron cell death and functional activity in refining motor projections within muscles, including the matching of fast and slow motoneurons and muscle fibers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019640-06
Application #
3399744
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1983-01-01
Project End
1992-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
6
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Connecticut
Department
Type
Schools of Arts and Sciences
DUNS #
City
Storrs-Mansfield
State
CT
Country
United States
Zip Code
06269
Hata, Katsusuke; Maeno-Hikichi, Yuka; Yumoto, Norihiro et al. (2018) Distinct Roles of Different Presynaptic and Postsynaptic NCAM Isoforms in Early Motoneuron-Myotube Interactions Required for Functional Synapse Formation. J Neurosci 38:498-510
Kastanenka, Ksenia V; Landmesser, Lynn T (2013) Optogenetic-mediated increases in in vivo spontaneous activity disrupt pool-specific but not dorsal-ventral motoneuron pathfinding. Proc Natl Acad Sci U S A 110:17528-33
Maeno-Hikichi, Yuka; Polo-Parada, Luis; Kastanenka, Ksenia V et al. (2011) Frequency-dependent modes of synaptic vesicle endocytosis and exocytosis at adult mouse neuromuscular junctions. J Neurosci 31:1093-105
Park, Gyu-Hwan; Maeno-Hikichi, Yuka; Awano, Tomoyuki et al. (2010) Reduced survival of motor neuron (SMN) protein in motor neuronal progenitors functions cell autonomously to cause spinal muscular atrophy in model mice expressing the human centromeric (SMN2) gene. J Neurosci 30:12005-19
Kastanenka, Ksenia V; Landmesser, Lynn T (2010) In vivo activation of channelrhodopsin-2 reveals that normal patterns of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules. J Neurosci 30:10575-85
Wang, Sheng; Polo-Parada, Luis; Landmesser, Lynn T (2009) Characterization of rhythmic Ca2+ transients in early embryonic chick motoneurons: Ca2+ sources and effects of altered activation of transmitter receptors. J Neurosci 29:15232-44
Kariya, Shingo; Park, Gyu-Hwan; Maeno-Hikichi, Yuka et al. (2008) Reduced SMN protein impairs maturation of the neuromuscular junctions in mouse models of spinal muscular atrophy. Hum Mol Genet 17:2552-69
Hanson, M Gartz; Milner, Louise D; Landmesser, Lynn T (2008) Spontaneous rhythmic activity in early chick spinal cord influences distinct motor axon pathfinding decisions. Brain Res Rev 57:77-85
Hata, Katsusuke; Polo-Parada, Luis; Landmesser, Lynn T (2007) Selective targeting of different neural cell adhesion molecule isoforms during motoneuron myotube synapse formation in culture and the switch from an immature to mature form of synaptic vesicle cycling. J Neurosci 27:14481-93
Herlitze, Stefan; Landmesser, Lynn T (2007) New optical tools for controlling neuronal activity. Curr Opin Neurobiol 17:87-94

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