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Author Notes:

Corresponding Author: Francisco J. Alvarez, Department of Physiology, Emory University School of Medicine, Whitehead Research Building, Room 642, 615 Michael Street, Atlanta, GA, 30322-3110, Phone 404-727-5139, francisco.j.alverez@emory.edu

Dr. George Z. Mentis read the manuscript and provided invaluable input.

Role of Authors: Study concept and design: FJA. Acquisition of data and statistical analyses: VCS, LG-P, TMR & FJA. Drafting and critical revision of manuscript: FJA, VCS & NAS. Study supervision: FJA & NAS.

We thank Mrs. Courtney Smith for her help with histology processing and Mrs. Maria C. Berrocal for maintaining some of the mouse colonies used.

The Er81 knockout line was generously provided by Dr. T.M. Jessell (Columbia University, NY).

There are no known conflicts of interest that would have inappropriately influenced the work.

Note added in proof: The initial preliminary communication of Bikoff et al., 2012 cited in here has now been accepted for publication in a full length article.

Subjects:

Research Funding:

This work was supported by NIH grant NS047357 to FJA and by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NAS).

VCS was in part supported by the Biomedical Sciences PhD program at Wright State University.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Zoology
  • Neurosciences & Neurology
  • spinal cord
  • VGLUT1
  • VAChT
  • development
  • calbindin
  • parvalbumin
  • Ia afferent
  • motoneuron
  • RAT SPINAL-CORD
  • CALCIUM-BINDING PROTEINS
  • VESICULAR GLUTAMATE TRANSPORTERS
  • SPINDLE-DERIVED NEUROTROPHIN-3
  • CEREBELLAR PURKINJE-CELLS
  • TRANSCRIPTION FACTOR EGR3
  • DORSAL-ROOT GANGLIA
  • POSTNATAL-DEVELOPMENT
  • GLYCINE RECEPTOR
  • HINDLIMB MUSCLES

Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells

Tools:

Journal Title:

Journal of Comparative Neurology

Volume:

Volume 524, Number 9

Publisher:

, Pages 1892-1919

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81-/- knockout), weakened (Egr3-/- knockout), or strengthened (mlcNT3+/- transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. J. Comp. Neurol. 524:1892-1919, 2016.

Copyright information:

© 2016 Wiley Periodicals, Inc. This is the peer reviewed version of the following article, which has been published in final form. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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