Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell - motor neuron circuit

2017-05-08

Spinal cord

Interneurons

Nicotinic acetylcholine receptor alpha2

mouse

VIAAT

VGAT

ChAT

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 alpha 2 (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, nor did it 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.

Enjin A, Perry S, Hilscher MM, Nagaraja C, Larhammar M, Gezelius H, Eriksson A, Leão KE, Kullander K (2017) Developmental disruption of recurrent inhibitory feedback results in compensatory adaptation in the Renshaw cell - motor neuron circuit. J Neurosci. May 8. pii: 0949-16. doi: 10.1523/JNEUROSCI.0949-16.2017.