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.
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.
|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|
|McLean, David L; Fetcho, Joseph R (2011) Movement, technology and discovery in the zebrafish. Curr Opin Neurobiol 21:110-5|
|Farrar, Matthew J; Wise, Frank W; Fetcho, Joseph R et al. (2011) In vivo imaging of myelin in the vertebrate central nervous system using third harmonic generation microscopy. Biophys J 100:1362-71|
|Koyama, Minoru; Kinkhabwala, Amina; Satou, Chie et al. (2011) Mapping a sensory-motor network onto a structural and functional ground plan in the hindbrain. Proc Natl Acad Sci U S A 108:1170-5|
|Kinkhabwala, Amina; Riley, Michael; Koyama, Minoru et al. (2011) A structural and functional ground plan for neurons in the hindbrain of zebrafish. Proc Natl Acad Sci U S A 108:1164-9|
|Fetcho, Joseph R; McLean, David L (2010) Some principles of organization of spinal neurons underlying locomotion in zebrafish and their implications. Ann N Y Acad Sci 1198:94-104|
|McLean, David L; Fetcho, Joseph R (2009) Spinal interneurons differentiate sequentially from those driving the fastest swimming movements in larval zebrafish to those driving the slowest ones. J Neurosci 29:13566-77|
|Hale, M E; Ritter, D A; Fetcho, J R (2001) A confocal study of spinal interneurons in living larval zebrafish. J Comp Neurol 437:1-16|
|Eaton, R C; Hofve, J C; Fetcho, J R (1995) Beating the competition: the reliability hypothesis for Mauthner axon size. Brain Behav Evol 45:183-94|