CENTRAL CONTROL OF MOTONEURONS IN A VERTEBRATE

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Movements are produced by activity in populations of neurons, but little is known about the patterns of recruitment in neuronal populations and their relationships to behavior. This proposal outlines studies of how different forms of a simple vertebrate behavior-the escape behavior in zebrafish-are produced by activity in pools of hindbrain reticulospinal neurons and spinal interneurons. The work uses powerful new imaging techniques that take advantage of the transparency of larval zebrafish and allow the imaging of activity in cells in the intact animal, as well as the photoablation of cells to study the resulting behavior changes. The aims are: 1) to use photoabalations to test the hypothesis that the hindbrain contains serially repeated sets of functionally related reticulospinal neurons that act as a population to produce escape turns of different magnitudes; 2) To use photoablations to provide the first direct test of the functional role of at a class of spinal interneuron in a behavior; 3) To use calcium imaging to study how the spinal interneurons in a population are recruited during movements (escapes) of different strength and; 4) To use ablations, combined with imaging of activity, to study the links between reticulospinal activity and spinal interneuron recruitment. The work is of general importance because many of the descending commands for movement from the brain are channeled through the reticulospinal system and spinal interneurons, but we know little about the patterns of activity in these neuronal populations and their contributions to behavior. Each of the proposed aims not only provides a piece of the information needed for better understanding of one behavior, they also address fundamental issues in the control of movement that will apply broadly among vertebrates. These include the functional significance of hindbrain segmentation, the behavioral role of spinal interneurons, patterns of interneuron recruitment, and the links between reticulospinal neurons, premotor interneurons and behavior. The work is basic research dealing with principals of motor organization. The establishment of the principals by which normal movements are produced provides the foundation for understanding the disruptions of movement that occur in various diseases. The work is of additional significance because of the increasing importance of zebrafish as at a model system in development and genetics. The power of the eventual combination of development, genetics, functional imaging and behavioral studies make the further development of this model system especially important.