The proposed experiments are components of a research effort whose long-term objective is to understand the role played by the spinal cord in the control of voluntary movements of the primate arm. This goal includes a search for therapies or interventions that will overcome the motor deficits associated with spinal cord injury. The proposed study advances these goals by elucidating the functional organization of spinal interneurons controlling forearm movements in the normal, behaving monkey. A thorough understanding of normal spinal function is essential before studies of motor impairment and recovery following injury can be interpreted usefully.
The specific aims of the project are: 1. What is the role of propriospinal interneurons located rostral to the cervical enlargement in the control of primate arm and hand movements? 2. How are motoneuron and interneuron excitability regulated during normal movements by inhibitory mechanisms in the spinal cord? 3. Is the normal activity of spinal motoneurons during voluntary movement dependent on the action of monoamines? The activity of cervical neurons will be recorded during voluntary reaching, isolated wrist movements, and cocontraction of flexor and extensor muscles of the wrist in the awake monkey. Inhibitory and neuromodulator inputs to spinal neurons will be manipulated with local iontophoresis of pharmacological agents that activate or block serotonin, noradrenaline, GABA or glycine receptors. Input and output connections of interneurons will be identified with spike-triggered averages of EMG and natural and electrical stimulation of peripheral afferents and descending pathways. These studies will elucidate the mechanisms by which the excitability of interneurons and motoneurons are controlled during voluntary movements and lay the foundation for future studies on the mechanisms of motor dysfunction and recovery from injury. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040867-07
Application #
7058723
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Chen, Daofen
Project Start
2000-09-28
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
7
Fiscal Year
2006
Total Cost
$361,306
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Nishimura, Yukio; Perlmutter, Steve I; Eaton, Ryan W et al. (2013) Spike-timing-dependent plasticity in primate corticospinal connections induced during free behavior. Neuron 80:1301-9
Wu, Guoji; Perlmutter, Steve I (2013) Sensitivity of spinal neurons to GABA and glycine during voluntary movement in behaving monkeys. J Neurophysiol 109:193-201
Nishimura, Yukio; Perlmutter, Steve I; Fetz, Eberhard E (2013) Restoration of upper limb movement via artificial corticospinal and musculospinal connections in a monkey with spinal cord injury. Front Neural Circuits 7:57
Cohen, Oren; Sherman, Efrat; Zinger, Nofya et al. (2010) Getting ready to move: transmitted information in the corticospinal pathway during preparation for movement. Curr Opin Neurobiol 20:696-703
Seki, Kazuhiko; Perlmutter, Steve I; Fetz, Eberhard E (2009) Task-dependent modulation of primary afferent depolarization in cervical spinal cord of monkeys performing an instructed delay task. J Neurophysiol 102:85-99
Moritz, Chet T; Perlmutter, Steve I; Fetz, Eberhard E (2008) Direct control of paralysed muscles by cortical neurons. Nature 456:639-42
Lasiene, Jurate; Shupe, Larry; Perlmutter, Steve et al. (2008) No evidence for chronic demyelination in spared axons after spinal cord injury in a mouse. J Neurosci 28:3887-96
Moritz, Chet T; Lucas, Timothy H; Perlmutter, Steve I et al. (2007) Forelimb movements and muscle responses evoked by microstimulation of cervical spinal cord in sedated monkeys. J Neurophysiol 97:110-20