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Developmental Disruption of Recurrent Inhibitory Feedback Results in Compensatory Adaptation in the Renshaw Cell-Motor Neuron Circuit

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Enjin, A, Perry, S, Hilscher, MM, Nagaraja, C, Larhammar, M, Gezelius, H, Eriksson, A, Leao, KE and Kullander, K 2017 , 'Developmental Disruption of Recurrent Inhibitory Feedback Results in Compensatory Adaptation in the Renshaw Cell-Motor Neuron Circuit' , Journal of Neuroscience, vol. 37, no. 23 , pp. 5634-5647 , doi: 10.1523/JNEUROSCI.0949-16.2017.

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Abstract

When activating muscles, motor neurons in the spinal cord also activate Renshaw cells, which provide recurrent inhibitory feedback to the motor neurons. The tight coupling with motor neurons suggests that Renshaw cells have an integral role in movement, a role that is yet to be elucidated. Here we used the selective expression of the nicotinic cholinergic receptor α2 (Chrna2) in mice to genetically target the vesicular inhibitory amino acid transporter (VIAAT) in Renshaw cells. Loss of VIAAT from Chrna2Cre -expressing Renshaw cells did not impact any aspect of drug-induced fictive locomotion in the neonatal mouse or change gait, motor coordination, or grip strength in adult mice of both sexes. However, motor neurons from neonatal mice lacking VIAAT in Renshaw cells received spontaneous inhibitory synaptic input with a reduced frequency, showed lower input resistance, and had an increased number of proprioceptive glutamatergic and calbindin-labeled putative Renshaw cell synapses on their soma and proximal dendrites. Concomitantly, Renshaw cells developed with increased excitability and a normal number of cholinergic motor neuron synapses, indicating a compensatory mechanism within the recurrent inhibitory feedback circuit. Our data suggest an integral role for Renshaw cell signaling in shaping the excitability and synaptic input to motor neurons.Significance statement: We here provide a deeper understanding of spinal cord circuit formation and the repercussions for the possible role for Renshaw cells in speed and force control. Our results suggest that while Renshaw cells are not directly required as an integral part of the locomotor coordination machinery, the development of their electrophysiological character is dependent on vesicular inhibitory amino acid transporter-mediated signaling. Further, Renshaw cell signaling is closely associated with the molding of motor neuron character proposing the existence of a concerted maturation process, which seems to endow this particular spinal cord circuit with the plasticity to compensate for loss of the Renshaw cell in adult circuit function.

Item Type: Article
Authors/Creators:Enjin, A and Perry, S and Hilscher, MM and Nagaraja, C and Larhammar, M and Gezelius, H and Eriksson, A and Leao, KE and Kullander, K
Keywords: ChAT; Chrna2; mouse; spinal cord; VIAAT
Journal or Publication Title: Journal of Neuroscience
Publisher: Soc Neuroscience
ISSN: 0270-6474
DOI / ID Number: 10.1523/JNEUROSCI.0949-16.2017
Copyright Information:

Copyright 2017 the authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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