Spinal lumbar dI2 interneurons contribute to stability of bipedal stepping

Abstract

Peripheral and intraspinal feedback is required to shape and update the output of spinal networks that execute motor behavior. We report that lumbar dI2 spinal interneurons in chicks receive synaptic input from afferents and premotor neurons. These interneurons innervate contralateral premotor networks in the lumbar and brachial spinal cord, and their ascending projections innervate the cerebellum. These findings suggest that dI2 neurons function as interneurons in local lumbar circuits, are involved in lumbo-brachial coupling, and that part of them deliver peripheral and intraspinal feedback to the cerebellum. Silencing of dI2 neurons leads to destabilized stepping in P8 hatchlings, with occasional collapses, variable step profiles and a wide-base walking gait, suggesting that dI2 neurons may contribute to the stabilization of the bipedal gait.

Proximal and distal spinal neurons innervating multiple synergist and antagonist motor pools

“…Since we have shown that LDPNs are negative for GlyT2 and ChAT and dI4 and dIL A INs are dorsal neurons ( Glasgow et al, 2005 ; Pillai et al, 2007 ) expression of Lhx1 would point to cervical LDPNs belonging to either the V0 V or dI2 class. In fact, it has very recently been shown that dorsally derived excitatory dI2 INs migrate to this region in the chick spinal cord and have divergent axons along the length of the cord and to the cerebellum ( Haimson et al, 2021 ). While these neurons are not premotor in the chick ( Haimson et al, 2021 ), it is possible that they are in the mouse.…”

“…In fact, it has very recently been shown that dorsally derived excitatory dI2 INs migrate to this region in the chick spinal cord and have divergent axons along the length of the cord and to the cerebellum ( Haimson et al, 2021 ). While these neurons are not premotor in the chick ( Haimson et al, 2021 ), it is possible that they are in the mouse.…”

“…Given the poor detection of the Lhx1 transcription factor in postnatal mice ( Figure 5—figure supplement 1 ), we could not conclude that the labelled cervical LDPNs are a population that derive from the V0 v or dI2 class. Although in the chick, dI2 INs do not project to MNs ( Haimson et al, 2021 ), it is possible that they could in the mouse: these are large neurons located in the ventromedial spinal cord ( Haimson et al, 2021 ), and express Lhx1 ( Avraham et al, 2009 ). Further experiments using a Dbx1-IRES-GFP mouse line ( Bouvier et al, 2010 ), for example, could help to determine the identity of these divergent cervical LDPNs.…”

Spinal cords: Symphonies of interneurons across species

“…From work in the cat, it has become clear that sensory inputs are important for initiating and maintaining an appropriate locomotor rhythm by regulating phase changes during stepping and modulating the amplitude of motor output ( Stuart and Hultborn, 2008 ). Dorsal interneurons also project supraspinally and receive descending input to regulate descending pathways ( Bourane et al, 2015 ; Haimson et al, 2021 ). Since dorsal spinal interneurons regulate these sensory pathways, one can be certain that they will exhibit large differences between water- and land-based animals, consistent with current observations of dorsal subtype radiation from zebrafish to mouse ( Figure 7 ).…”

“…In mice, very little is known about dI2 anatomy or function. A recent study in chick however, showed that dI2 neurons at limb levels receive sensory and premotor interneuron input, and project to the cerebellum ( Haimson et al, 2021 ). Silencing of dI2 neurons in chick results in abnormal hindlimb stepping ( Haimson et al, 2021 ), implicating them in the high-level coordination of limb movement.…”