These investigators have recently observed a robust change in rate-depression (a progressive decline in the monosynaptic reflex at low stimulation frequencies) in rats following the type of spinal cord injury which typically induces spasticity in humans. This experimental model provides an opportunity to determine some essential features of the neurosubstrate and cellular mechanisms of rate-depression. Preliminary data show that rate-depression is significantly reduced by blockade of GABAb receptors by intrathecal administration of a specific GABAb antagonist. However, both spinal and supraspinal sites could have accounted for these observations. Experiments in Specific Aim 1 are proposed using intraspinal microinjection of GABAb agonists and antagonists to identify specific sites within the spinal cord which alter rate-depression. These studies will more specifically define the segmental neural substrate and cellular mechanisms of action of rate-depression. Further evidence indicates that rate- depression can be significantly influenced by microstimulation of cell clusters in the brainstem which are associated with the densest spinal projection of serotonergic fibers. Therefore, insights into the descending control of rate-depression will be sought using microstimulation to identify brainstem neuron and fiber clusters which significantly alter the expression of rate-depression. These studies will increase understanding of the descending control of reflex excitability as well as account for changes which occur following spinal cord injury. Experiments in Specific Aim 2 will determine how specific changes in reflex excitability may correlate to the experimental manifestation of spastic hyperreflexia. These experiments will correlate the time course and magnitude of alterations in the dynamic stretch reflexes of lower leg calf muscles to specific changes in spinal reflex excitability following midthoracic spinal hemisection. In addition the specific role of GABAb receptors in the maintenance of normal muscle tone, as well as the development and persistence of spastic hypertonia of calf muscle dynamic stretch reflexes will be determined. In summary, the proposed experiments will increase our understanding of the mechanism and organization of a fundamental process which regulates motoneuron excitability and how changes in the mechanism may contribute to the development of spastic hypertonia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS033333-01A1
Application #
2272083
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1995-05-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Florida
Department
Neurosciences
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Wang, David C; Bose, Prodip; Parmer, Ronald et al. (2002) Chronic intrathecal baclofen treatment and withdrawal: I. Changes in ankle torque and hind limb posture in normal rats. J Neurotrauma 19:875-86
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Thompson, F J; Parmer, R; Reier, P J (1998) Alteration in rate modulation of reflexes to lumbar motoneurons after midthoracic spinal cord injury in the rat. I. Contusion injury. J Neurotrauma 15:495-508
Thompson, F J; Browd, C R; Carvalho, P M et al. (1996) Velocity-dependent ankle torque in the normal rat. Neuroreport 7:2273-6