Dmrt3 cells and Renshaw cells in spinal motor circuits

Spinal cord interneurons coordinate locomotion and the integration with descending signals from motor centers in the brain. The direct link between circuit activity in the locomotor CPG and motor output makes it well suited for elucidating the assembly and identity of the participating neurons.

One of the first inhibitory interneuron characterized is the Renshaw cell, which is located in the ventral horn of the spinal cord and mediate recurrent inhibition of alpha motor neurons. While the RC act of recurrent inhibition is known since a long time, the exact function of these cells in motor control is yet to be established. Renshaw cells have been shown to be rhythmically active during fictive locomotion, both in cat and mouse and are likely involved in control of the speed of locomotion, however, an unambiguous role of Renshaw cells is yet to be found. Interestingly, we have found that Renshaw cells are positioned to provide disinhibition (Wootz et al., JCN, 2013, 521:1449-1469) and have been shown to be spontaneously active at rest, firing at a resting rate of 7 Hz (Perry et al., Eur J Neurosci. 2015, 41:889-900).

Schematic of the Dmrt3 neurons (red) and relation to motor neurons (blue) in the mouse spinal cord.
Figure 4. Schematic of the Dmrt3 neurons (red) and relation to motor neurons (blue) in the mouse spinal cord.
 

We previously found that the Dmrt3 gene has a major effect on the pattern of locomotion in mice and horses (Andersson et al., Nature 2012, 488:642-6). This positioned the Dmrt3 gene in a pivotal role for configuring the spinal circuits controlling stride in vertebrates. In a follow-up study, we establish that Dmrt3 expressing neurons is, at least in part, responsible for the observed effects in the locomotor network (Perry et al., 2018, in revision JNS). Moreover, we found that Dmrt3 neurons are inhibitory, connect directly to motor neurons and receive inhibitory, excitatory and modulatory inputs. We now continue to define the function of neurons coordinating the locomotor circuits in the mammalian spinal cord with a focus on the functional roles of Dmrt3 interneurons and Renshaw cells.