The larval lamprey exhibits axonal regeneration and functional recovery following spinal cord lesions. However, the PI has found that by altering the temperature at which animals are maintained, it is possible to produce animals that exhibit either functional or dysfunctional swimming behavior. Thus the lamprey offers the opportunity to study the nature and consequences of dysfunctional regeneration. She has further found anatomical differences between the regenerated systems under the two conditions, specifically in terms of the distribution of serotoninergic axons. Following transections, there is a dramatic increase in serotonin fibers in areas rostral to the lesion, and a dramatic loss in caudal segments. However under conditions that favor recovery, serotonin fibers are more abundant in the caudal segments. She hypothesizes that serotonin fibers are responsible for at least one form of the behavioral differences seen under the different temperature conditions. The PI now proposes to identify the sources of the increased serotonin innervation in rostral segments, and the fate of the lost serotonin in caudal segments. One possibility that will be explored is that the increases in caudal segments is due to collareral sprouting of descending serotonin systems. She will test this hypothesis by evaluating whether the serotonin fibers originate from the brainstem or from dorsal roots. The fate of dopamine fibers will also be evaluated. Other studies will evaluate the functional capabilities of the animals using a sophisticated stochastic phase model to evaluate physiological responses. This technique, which has been developed by the PI, provides a quantitative measure of the degree of coordination between segments. In the same animals, the regenerated fibers will be traced anatomically and using specific markers for GABA and glycine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039909-02
Application #
6363962
Study Section
Special Emphasis Panel (ZRG1-BDCN-2 (01))
Program Officer
Kleitman, Naomi
Project Start
2000-03-28
Project End
2004-02-28
Budget Start
2001-03-01
Budget End
2002-02-28
Support Year
2
Fiscal Year
2001
Total Cost
$213,357
Indirect Cost
Name
University of Maryland College Park
Department
Biology
Type
Schools of Earth Sciences/Natur
DUNS #
City
College Park
State
MD
Country
United States
Zip Code
20742
Ayali, A; Fuchs, E; Ben-Jacob, E et al. (2007) The function of intersegmental connections in determining temporal characteristics of the spinal cord rhythmic output. Neuroscience 147:236-46
Boothe, David L; Cohen, Avis H; Troyer, Todd W (2006) Temporal correlations in stochastic models of double bursting during simulated locomotion. J Neurophysiol 95:1556-70
Cohen, Avis H; Abdelnabi, Mahmoud; Guan, Li et al. (2005) Changes in distribution of serotonin induced by spinal injury in larval lampreys: evidence from immunohistochemistry and HPLC. J Neurotrauma 22:172-88
Kiemel, Tim; Gormley, Kevin M; Guan, Li et al. (2003) Estimating the strength and direction of functional coupling in the lamprey spinal cord. J Comput Neurosci 15:233-45