title: Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells.
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.
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, 45435.
authors.forename: Valerie C
authors.initials: VC
authors.lastname: Siembab
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Laura
authors.initials: L
authors.lastname: Gomez-Perez
authors.affiliation: Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Travis M
authors.initials: TM
authors.lastname: Rotterman
authors.affiliation: Department of Neurology, Center for Motor Neuron Biology and Disease, Columbia University, New York, New York, 10032.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Shneider
authors.affiliation: Department of Neuroscience, Cell Biology and Physiology, Boonshoft School of Medicine, Wright State University, Dayton, Ohio, 45435.|Department of Physiology, Emory University School of Medicine, Atlanta, Georgia, 30322.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alvarez
mesh_terms: D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D064026:Calbindins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D051776:Early Growth Response Protein 3 / Q000172:deficiency / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000166:cytology*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D066293:Renshaw Cells / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D064026:Calbindins; D004268:DNA-Binding Proteins; C497369:Egr3 protein, mouse; C490641:Etv1 protein, mouse; D009414:Nerve Growth Factors; D010320:Parvalbumins; C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D014157:Transcription Factors; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; C518911:neurotropin 3, mouse; D051776:Early Growth Response Protein 3; D010751:Phosphopyruvate Hydratase
keywords: Ia afferent; VAChT; VGLUT1; calbindin; development; motoneuron; parvalbumin; spinal cord