The long-term goal of this project is to understand the consequences of the loss of short-latency proprioceptive feedback for motor coordination during locomotion and targeted reaching. Self-reinnervation of muscle following transection of the nerve can lead to a permanent loss of effective proprioceptive feedback. Peripheral nerve injury can also lead to a long-term disruption of dexterity or motor coordination, even after regrowth of the nerve. The central hypothesis for this project is that sensory feedback from muscle prioprioceptors provides ongoing regulation of coordination and during voluntary motor behavior, and that the loss of this feedback leads to permanent deficits in motor coordination. This hypothesis will be tested by using the method of self- reinnervation to remove effective feedback from selected muscles in the cat and evaluating the motor performance of these animals following the restoration of motor power. The intermuscular distribution of proprioceptive feedback from muscle spindle receptors and Golgi tendon organs will first be determined. Actions of these pathways will be measured by stretching individual muscles or perturbing the forelimb in decerebrate animals and then measuring the resulting force or electromyographic responses. These data will be used to determine the most important sources of sensory feedback. Motor deficits resulting from loss of this feedback will be evaluated in otherwise intact animals by causing the self-reinnervation of selected muscles that supply critical feedback to other muscles in the forelimb. Animals will be filmed during locomotion on ramp surfaces or during targeted reaching movements. Based on similar studies using the hindlimb, the removal of effective feedback is expected to produce a loss of interjoint coordination down a ramp and difficulty in terminating movements of the forelimb. The ability of these animals to compensate for these deficits will be evaluated by long-term experience on the behavioral task. This project will constitute an evaluation of the role of sensory feedback from muscles on the coordination of voluntary movements and of the mechanisms underlying the loss of coordination following peripheral nerve injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS040405-03
Application #
6645014
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2002-07-01
Project End
2003-06-30
Budget Start
Budget End
Support Year
3
Fiscal Year
2002
Total Cost
$55,743
Indirect Cost
Name
Emory University
Department
Type
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Livingston, Beven P; Nichols, T Richard (2014) Effects of reinnervation of the triceps brachii on joint kinematics and electromyographic patterns of the feline forelimb during level and upslope walking. Cells Tissues Organs 199:405-22
Livingston, Beven P; Nichols, T Richard (2014) Effects of reinnervation of the biarticular shoulder-elbow muscles on joint kinematics and electromyographic patterns of the feline forelimb during downslope walking. Cells Tissues Organs 199:423-40
Conforti, L; Fang, G; Beirowski, B et al. (2007) NAD(+) and axon degeneration revisited: Nmnat1 cannot substitute for Wld(S) to delay Wallerian degeneration. Cell Death Differ 14:116-27
Rich, Mark M; Wenner, Peter (2007) Sensing and expressing homeostatic synaptic plasticity. Trends Neurosci 30:119-25
Rich, Mark M (2006) The control of neuromuscular transmission in health and disease. Neuroscientist 12:134-42
Wang, Xueyong; Engisch, Kathrin L; Teichert, Russell W et al. (2006) Prolongation of evoked and spontaneous synaptic currents at the neuromuscular junction after activity blockade is caused by the upregulation of fetal acetylcholine receptors. J Neurosci 26:8983-7
Wang, Xueyong; Li, Yingjie; Engisch, Kathrin L et al. (2005) Activity-dependent presynaptic regulation of quantal size at the mammalian neuromuscular junction in vivo. J Neurosci 25:343-51
Nichols, T Richard; Cope, Timothy C (2004) Cross-bridge mechanisms underlying the history-dependent properties of muscle spindles and stretch reflexes. Can J Physiol Pharmacol 82:569-76
Fischer, Lindsey R; Culver, Deborah G; Tennant, Philip et al. (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185:232-40
Haftel, Valerie K; Bichler, Edyta K; Nichols, T Richard et al. (2004) Movement reduces the dynamic response of muscle spindle afferents and motoneuron synaptic potentials in rat. J Neurophysiol 91:2164-71

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