Most vertebrate behaviors depend on the coordinated activity of many neurons in the brain and/or spinal cord. While the organization and function of single iterations of spinal cord circuits have been examined, it is unknown how interneuron populations distributed across segments generate functional behaviors. The goal of this research is to examine the longitudinal distribution of spinal cord interneurons and the roles of those interneuron populations in behavior. This work takes advantage of novel techniques for neuron imaging in the larval zebrafish model system, including cell population activity imaging and cell-specific ablation techniques, to test hypotheses of interneuron organization and function.
Aim 1 examines the longitudinal distributions of spinal cord interneurons testing the hypothesis that there is a rostrocaudal gradient in cell and population size of descending interneurons in motor circuits.
Aim 2 determines the roles of descending interneurons in behavior. Cell-specific lesioning is used to remove a population of interneurons and behavior is assessed before and after those ablations.
Aim 2 tests the hypotheses that removing descending excitatory interneurons will decrease bending amplitude, angular velocity, angular acceleration and, for rhythmic movements, disrupt the pattern of axial wave propagation. This is the first test of the roles of spinal interneurons in vertebrates.
Aim 3 bridges Aim 1 and Aim 2 to address how interneurons effect their behavioral roles by imaging cell activity across a population of neurons downstream of the ablated cells. We hypothesize that ablating excitatory startle interneurons will decrease activity of interneurons and motoneurons in the ablation region in proportion to the number of ablated cells but will not alter caudal activity. We hypothesize that that ablating excitatory swim interneurons will decrease interneuron activity in and caudal to the region of the ablations.
The aims of this proposal address fundamental questions about interneuron population function in behaviors by testing the roles cells and in movement and in circuit function. By providing basic information on the neural control of movements, this work provides a foundation of information on how populations of interneurons function together to coordinate movement. Such work is critical for understanding the neural basis of movement disruption through injury and disease. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043977-03
Application #
6844671
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Gwinn, Katrina
Project Start
2003-03-15
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
3
Fiscal Year
2005
Total Cost
$213,572
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Skromne, Isaac; Thorsen, Dean; Hale, Melina et al. (2007) Repression of the hindbrain developmental program by Cdx factors is required for the specification of the vertebrate spinal cord. Development 134:2147-58
Thorsen, Dean H; Hale, Melina E (2007) Neural development of the zebrafish (Danio rerio) pectoral fin. J Comp Neurol 504:168-84
Bhatt, Dimple H; McLean, David L; Hale, Melina E et al. (2007) Grading movement strength by changes in firing intensity versus recruitment of spinal interneurons. Neuron 53:91-102
Thorsen, D H; Hale, M E (2005) Development of zebrafish (Danio rerio) pectoral fin musculature. J Morphol 266:241-55
Hurley, I; Hale, M E; Prince, V E (2005) Duplication events and the evolution of segmental identity. Evol Dev 7:556-67
Thorsen, Dean H; Cassidy, Justin J; Hale, Melina E (2004) Swimming of larval zebrafish: fin-axis coordination and implications for function and neural control. J Exp Biol 207:4175-83
Hale, Melina E; Kheirbek, Mazen A; Schriefer, Julie E et al. (2004) Hox gene misexpression and cell-specific lesions reveal functionality of homeotically transformed neurons. J Neurosci 24:3070-6