Much of the ability to move depends upon networks of neurons in the spinal cord and hindbrain. Recent evidence indicates that there is a relatively simple structural and functional organization in spinal cord that may extend into the hindbrain. This proposal explores whether there is a basic template to the organization of neurons and their wiring in hindbrain that is established during development and that underlies the control of movement. Such a template would provide a conceptual organization that would enhance in a major way the understanding of the organization of a part of the brain that is critical for normal movement and whose proper function is disrupted in disease and after spinal injury. The proposed work stems from the discovery that neurons in hindbrain are clustered into stripes based on neurotransmitter. The proposal takes advantage of the ability to see into the brain and spinal cord of intact larval zebrafish to explore 1) whether the stripes correspond to transcription factors and how the stripes develop, 2) whether neurons within a stripe are similar to one another and project in a regular way to neurons in other stripes, 3) whether the electrical properties of neurons within a stripe vary systematically with their position and age in a way that might lead to their orderly activation during normal movements and 4) whether the position of a neuron in a stripe reflects the speed of the movement in which it is activated. The proposed work will reveal basic principles that link development with the later structure and function of neurons in the hindbrain. These will inform us about brain organization in vertebrates, including humans, and should help us to interpret and eventually treat movement disorders.

Public Health Relevance

The ability to move depends upon nerve cells located in the back part of the brain, the hindbrain. This proposal outlines experiments to examine how the hindbrain is organized to control movements. The work is important because the control of movement by the brain is disrupted in spinal injury as well as in genetic diseases that affect movement.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026539-24
Application #
8044864
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
1990-07-01
Project End
2014-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
24
Fiscal Year
2011
Total Cost
$451,328
Indirect Cost
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Parvez, Saba; Long, Marcus J C; Poganik, Jesse R et al. (2018) Redox Signaling by Reactive Electrophiles and Oxidants. Chem Rev 118:8798-8888
Farrar, Matthew J; Kolkman, Kristine E; Fetcho, Joseph R (2018) Features of the structure, development, and activity of the zebrafish noradrenergic system explored in new CRISPR transgenic lines. J Comp Neurol 526:2493-2508
Chow, Dawnis M; Zuchowski, Kathryn A; Fetcho, Joseph R (2017) In Vivo Measurement of Glycine Receptor Turnover and Synaptic Size Reveals Differences between Functional Classes of Motoneurons in Zebrafish. Curr Biol 27:1173-1183
McArthur, Kimberly L; Fetcho, Joseph R (2017) Key Features of Structural and Functional Organization of Zebrafish Facial Motor Neurons Are Resilient to Disruption of Neuronal Migration. Curr Biol 27:1746-1756.e5
Long, Marcus John Curtis; Aye, Yimon (2017) Privileged Electrophile Sensors: A Resource for Covalent Drug Development. Cell Chem Biol 24:787-800
Long, Marcus J C; Parvez, Saba; Zhao, Yi et al. (2017) Akt3 is a privileged first responder in isozyme-specific electrophile response. Nat Chem Biol 13:333-338
Koyama, Minoru; Minale, Francesca; Shum, Jennifer et al. (2016) A circuit motif in the zebrafish hindbrain for a two alternative behavioral choice to turn left or right. Elife 5:
Chen, Shijia; Chiu, Cindy N; McArthur, Kimberly L et al. (2016) TRP channel mediated neuronal activation and ablation in freely behaving zebrafish. Nat Methods 13:147-50
Kishore, Sandeep; Fetcho, Joseph R (2013) Homeostatic regulation of dendritic dynamics in a motor map in vivo. Nat Commun 4:2086
Liao, James C; Haehnel, Melanie (2012) Physiology of afferent neurons in larval zebrafish provides a functional framework for lateral line somatotopy. J Neurophysiol 107:2615-23

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