Knowledge of the organization and function of spinal systems is a critical need in developing therapies for motor dysfunction that accompany spinal injury and neurological disease. To achieve this goal, the longrange objective of this application is to determine how motoneuron pools are coordinated and regulated during motor activities.
The specific aims of this application are based on the proposal that Renshaw recurrent inhibition regulates the activity of sets of motoneurons and associated la interneurons coactivated by common excitatory drives produced by spinal pattern generators. This possibility will be explored by testing two hypotheses. Studies for the first specific aim will test the hypothesis that rhythmic motor commands during locomotion and scratching are distributed to motor nuclei and their associated la reciprocal inhibitory interneurons. Experimental support for this hypothesis would establish a parallel distribution of rhythmic drive signals to motoneurons and associated la interneurons as a fundamental feature in the organization of spinal pattern generators. Studies for the second specific aim will test the hypothesis that rhythmic motor commands generated by spinal networks are organized to maintain separate excitatory drives to motor nuclei that innervate antagonist muscles and that are linked by la reciprocal inhibition. Reciprocal inhibition is a common feature of the spinal organization of motoneurons, la reciprocal inhibitory interneurons and Renshaw cells, yet spinal pattern generation can involve coactivation of motor nuclei whose muscles are mechanical antagonists as well as reciprocal activation. We propose that conditions for adequate control by these reciprocally inhibitory networks and the need for such adaptability in producing motor patterns are both satisfied by restricting motoneuron projections from individual sets of pattern generating neurons to pools that do not include these reciprocal inhibitory connections. The planned studies will provide fundamental information concerning the organization of spinal networks involved in pattern generation and motor control. In addition, the information obtained will provide insight into the roles that spinal mechanisms play in motor dysfunction following spinal injury and neurological disease and will help guide the development of therapies for the treatment of these disorders, such as the use of spinal cord stimulation following spinal injury. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS022454-17
Application #
6584252
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (02))
Program Officer
Chen, Daofen
Project Start
1986-04-01
Project End
2006-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
17
Fiscal Year
2003
Total Cost
$335,302
Indirect Cost
Name
St. Joseph's Hospital and Medical Center
Department
Type
DUNS #
131606022
City
Phoenix
State
AZ
Country
United States
Zip Code
85013
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Maltenfort, Mitchell G; McCurdy, Martha L; Phillips, Carrie A et al. (2004) Location and magnitude of conductance changes produced by Renshaw recurrent inhibition in spinal motoneurons. J Neurophysiol 92:1417-32
Maltenfort, Mitchell G; Phillips, Carrie A; McCurdy, Martha L et al. (2004) Determination of the location and magnitude of synaptic conductance changes in spinal motoneurons by impedance measurements. J Neurophysiol 92:1400-16
Trank, T V; Turkin, V V; Hamm, T M (1999) Organization of recurrent inhibition and facilitation in motoneuron pools innervating dorsiflexors of the cat hindlimb. Exp Brain Res 125:344-52
Hamm, T M; Trank, T V; Turkin, V V (1999) Correlations between neurograms and locomotor drive potentials in motoneurons during fictive locomotion: implications for the organization of locomotor commands. Prog Brain Res 123:331-9
Turkin, V V; Monroe, K S; Hamm, T M (1998) Organization of recurrent inhibition and facilitation in motor nuclei innervating ankle muscles of the cat. J Neurophysiol 79:778-90
McCurdy, M L; Hamm, T M (1994) Topography of recurrent inhibitory postsynaptic potentials between individual motoneurons in the cat. J Neurophysiol 72:214-26
McCurdy, M L; Hamm, T M (1994) Spatial and temporal features of recurrent facilitation among motoneurons innervating synergistic muscles of the cat. J Neurophysiol 72:227-34
McCurdy, M L; Hamm, T M (1992) Recurrent collaterals of motoneurons projecting to distal muscles in the cat hindlimb. J Neurophysiol 67:1359-66
Hamm, T M (1990) Recurrent inhibition to and from motoneurons innervating the flexor digitorum and flexor hallucis longus muscles of the cat. J Neurophysiol 63:395-403