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

• Published in: Journal of comparative neurology (1911) 2016-06, Vol.524 (9), p.1892-1919
• Main Authors: Siembab, Valerie C., Gomez-Perez, Laura, Rotterman, Travis M., Shneider, Neil A., Alvarez, Francisco J.
• Format: Article
• Language: English
• Subjects: Afferent Pathways - physiology; Animals; Animals, Newborn; Axons - metabolism; calbindin; Calbindins - metabolism; development; DNA-Binding Proteins - deficiency; DNA-Binding Proteins - genetics; Early Growth Response Protein 3 - deficiency; Early Growth Response Protein 3 - genetics; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Ia afferent; Mice; Mice, Transgenic; motoneuron; Motor Neurons - cytology; Nerve Growth Factors - genetics; Nerve Growth Factors - metabolism; parvalbumin; Parvalbumins - metabolism; Phosphopyruvate Hydratase - metabolism; Renshaw Cells - physiology; spinal cord; Spinal Cord - cytology; Synapses - genetics; Synapses - physiology; Transcription Factors - deficiency; Transcription Factors - genetics; VAChT; Vesicular Glutamate Transport Protein 1 - metabolism; Vesicular Glutamate Transport Protein 2 - metabolism; VGLUT1
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.23946

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. © 2016 Wiley Periodicals, Inc. Renshaw cells receive convergent inputs from Ia afferents and motor axons during early development. The authors show that strengthening Ia afferent inputs decreases the number of synapses from motor axons and that decreasing Ia afferent inputs increases motor axon synapses. Therefore, they conclude that Ia afferents heterosynaptically modulate motor axon synapse numbers on Renshaw cells during postnatal development.