The lamprey has the property that its spinal cord spontaneously recovers from injury. There is ample evidence for fiber regrowth and functional recovery within a behaviorally relevant circuit, the central pattern generator(CPG) for locomotion. However, we present evidence to suggest the functional recovery is better described as dysfunction as both coordination and rhythmic stability are disrupted by the regenerated fibers. We propose to study the origins of this dysfunction. Specifically 1) we will obtain evidence after spinal injury as to the completeness of the behavioral recovery by recording muscle activity from swimming animals under unrestrained conditions. 2) The intrinsic coordinating system of the same animals will be characterized in vitro during fictive locomotion. Thus, we will compare the behavioral recovery with the CPG and regenerated coordinating system. The origin of any disruption in a given cord will be compared to the EMG data from the same animal to determine the contribution of sensory and descending input to the recovery. 3) The origin of the disruption in the """"""""fictive""""""""pattern will be correlated with an anatomical analysis of the neurons that have regenerated in that cord. Behavioral recovery will be assessed in the same animals continuously from one week until 10 months after injury. In some animals, the spinal cords will be isolated and tested at variable times beginning one week after injury, to include samples over the 10 months of recover. 4) The relative strengths of regenerated ascending versus descending fibers will be compared by examination of the response to mechanical forcing at rostral or caudal ends of the spinal cord. We hypothesize that a component of the disruptive changes originates from adaptive changes occurring over the course of an animal's life to match changing sensory input and motor output. To further test this hypothesis, we will examine the physiological and anatomical changes that occur in lampreys during their long transformation from ammocoete to adult and compare the results to those of regenerates. We will also assess the relative strengths of ascending versus descending coordinating fibers in ammocoetes and transformers using the same methods as those used for regenerates. Two modeling strategies will be developed in parallel to help us to understand the changes in both the coordinating system and the oscillators. These strategies both employ dynamical systems theory. A new type of model may allow more use of changes in the properties of the oscillators but lacks the property that the elements are themselves oscillators. This property will also be added to the new models and the two sytems that are generated will be compared.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurology B Subcommittee 2 (NEUB)
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University of Maryland College Park
Schools of Earth Sciences/Natur
College Park
United States
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Cohen, A H; Kiemel, T; Pate, V et al. (1999) Temperature can alter the function outcome of spinal cord regeneration in larval lampreys. Neuroscience 90:957-65
Kiemel, T; Cohen, A H (1998) Estimation of coupling strength in regenerated lamprey spinal cords based on a stochastic phase model. J Comput Neurosci 5:267-84
Cohen, A H; Guan, L; Harris, J et al. (1996) Interaction between the caudal brainstem and the lamprey central pattern generator for locomotion. Neuroscience 74:1161-73
Bertram, R; Butte, M J; Kiemel, T et al. (1995) Topological and phenomenological classification of bursting oscillations. Bull Math Biol 57:413-39
Mellen, N; Kiemel, T; Cohen, A H (1995) Correlational analysis of fictive swimming in the lamprey reveals strong functional intersegmental coupling. J Neurophysiol 73:1020-30
Cohen, A H; Dobrov, T A; Li, G et al. (1990) The development of the lamprey pattern generator for locomotion. J Neurobiol 21:958-69
Cohen, A H (1988) Regenerated fibers of the lamprey spinal cord can coordinate fictive swimming in the presence of curare. J Neurobiol 19:193-8
Cohen, A H (1987) Effects of oscillator frequency on phase-locking in the lamprey central pattern generator. J Neurosci Methods 21:113-25
Cohen, A H; Mackler, S A; Selzer, M E (1986) Functional regeneration following spinal transection demonstrated in the isolated spinal cord of the larval sea lamprey. Proc Natl Acad Sci U S A 83:2763-6
Harris-Warrick, R M; Cohen, A H (1985) Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord. J Exp Biol 116:27-46