Mechanisms regulating the specificity and strength of muscle afferent inputs in the spinal cord

Authors

  • George Z. Mentis,

    1. Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
    Search for more papers by this author
  • Francisco J. Alvarez,

    1. Department of Neurosciences, Cell Biology and Physiology, Wright State University, Dayton, Ohio.
    Search for more papers by this author
  • Neil A. Shneider,

    1. Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
    2. Department of Neurology, Columbia University, New York, New York.
    3. Center for Motor Neuron Biology and Disease, Columbia University, New York, New York
    Search for more papers by this author
  • Valerie C. Siembab,

    1. Department of Neurosciences, Cell Biology and Physiology, Wright State University, Dayton, Ohio.
    Search for more papers by this author
  • Michael J. O’Donovan

    1. Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
    Search for more papers by this author

Address for correspondence: George Z. Mentis, Center for Motor Neuron Biology and Disease, Columbia University, P & S Building, Room 4-450, 630 W 168th Street, New York, NY 10032. gzmentis@columbia.edu

Abstract

We investigated factors controlling the development of connections between muscle spindle afferents, spinal motor neurons, and inhibitory Renshaw cells. Several mutants were examined to establish the role of muscle spindles, muscle spindle-derived NT3, and excess NT3 in determining the specificity and strength of these connections. The findings suggest that although spindle-derived factors are not necessary for the initial formation and specificity of the synapses, spindle-derived NT3 seems necessary for strengthening homonymous connections between Ia afferents and motor neurons during the second postnatal week. We also found evidence for functional monosynaptic connections between sensory afferents and neonatal Renshaw cells although the density of these synapses decreases at P15. We conclude that muscle spindle synapses are weakened on Renshaw cells while they are strengthened on motor neurons. Interestingly, the loss of sensory synapses on Renshaw cells was reversed in mice overexpresssing NT3 in the periphery, suggesting that different levels of NT3 are required for functional maintenance and strengthening of spindle afferent inputs on motor neurons and Renshaw cells.

Ancillary