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 short, premotor, 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 the neuromodulators serotonin and noradrenaline? What is the contribution of inhibition to the recruitment and spatial tuning of motoneurons and interneurons? The activity of cervical interneurons and motoneurons will be recorded during voluntary reaching, isolated wrist movements, and contraction of flexor- and extensor muscles of the wrist in the awake monkey. Initial double-labeling anatomical experiments will guide the search for propriospinal neurons by identifying the location of premotor interneurons in the C3-C4 segments that receive direct input from corticospinal fibers. 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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZNS1-SRB-L (01))
Program Officer
Heetderks, William J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Schools of Medicine
United States
Zip Code
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