Spinal lumbar dI2 interneurons contribute to stability of bipedal stepping.

Baruch Haimson,Yuval Cinnamon,Avihu Klar,Yoav Hadas,Nimrod Bernat,Artur Kania,Aharon Lev-Tov,Monica A Daley

doi:10.7554/elife.62001

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 posthatching day 8 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.

Highlights

The spinal cord integrates and relays the somatosensory inputs required for further execution of complex motor behaviors
We focused on deciphering the circuitry and function of dI2 neurons and their possible association with VSCT. dI2 INs are mainly excitatory neurons with commissural axonal projections To label dI2 neurons, axons, and terminals in the chick spinal cord, we used intersection between enhancers of two transcription factors (TFs) expressed by dI2 – Ngn1 and Foxd3 – via the expression of two recombinases (Cre and FLPo) and double conditional reporters (Figure 1-figure supplement 1A)
At E6, dI2 neurons assume a midlateral position along the dorsoventral axis (Figure 1B). Subsequently, dI2 neurons migrate medially, and at E17, comparable to postnatal day 4 (P4) of mice, most of them (70.7 % and 71.5% at the sciatic and the crural levels, respectively) dI2 INs were labeled as cells that expressed both the Foxd3 and Ngn1 enhancers (Avraham et al, 2009)

Summary

Introduction

The spinal cord integrates and relays the somatosensory inputs required for further execution of complex motor behaviors. Postmitotic dI2 neurons undergo ventral migration and are defined by the combinatorial expression of 63 Foxd3+/Lhx1+/Pou4f1+ TFs (Alaynick et al, 2011, Morikawa et al, 2009, Francius et al, 2013). None of these TFs is specific to dI2 neurons; rather, their combinatorial expression defines dI2. The lack of dI2-specific cell fate markers and the dynamic expression of the above TFs in other INs causes ambiguity regarding the molecular profile and outcome of late postmitotic dI2 neurons.

Methods

Results

Discussion

Conclusion