Abstract

Long descending propriospinal neurons (LDPNs) are interneurons that form direct connections between cervical and lumbar spinal circuits. LDPNs are involved in interlimb coordination and are important mediators of functional recovery after spinal cord injury (SCI). Much of what we know about LDPNs comes from a range of species, however, the increased use of transgenic mouse lines to better define neuronal populations calls for a more complete characterisation of LDPNs in mice. In this study, we examined the cell body location, inhibitory neurotransmitter phenotype, developmental provenance, morphology and synaptic inputs of mouse LDPNs throughout the cervical and upper thoracic spinal cord. LDPNs were retrogradely labelled from the lumbar spinal cord to map cell body locations throughout the cervical and upper thoracic segments. Ipsilateral LDPNs were distributed throughout the dorsal, intermediate and ventral grey matter as well as the lateral spinal nucleus and lateral cervical nucleus. In contrast, contralateral LDPNs were more densely concentrated in the ventromedial grey matter. Retrograde labelling in GlyT2GFP and GAD67GFP mice showed the majority of inhibitory LDPNs project either ipsilaterally or adjacent to the midline. Additionally, we used several transgenic mouse lines to define the developmental provenance of LDPNs and found that V2b positive neurons form a subset of ipsilaterally projecting LDPNs. Finally, a population of Neurobiotin (NB) labelled LDPNs were assessed in detail to examine morphology and plot the spatial distribution of contacts from a variety of neurochemically distinct axon terminals. These results provide important baseline data in mice for future work on their role in locomotion and recovery from SCI.

Highlights

  • The propriospinal system is comprised of spinal interneurons with longitudinal axonal projections that extend outside their segment of origin, forming a network that connects motor and sensory circuits throughout the length of the spinal cord

  • Inhibitory Long descending propriospinal neurons (LDPNs) were mapped in GlyT2GFP and GAD67GFP (GABAergic) mice

  • The only difference we found was the existence of a more dense population of LDPNs in the lateral spinal nucleus and lateral cervical nucleus (LSN/LCN) than that reported for other species (Burton and Loewy, 1976; Molenaar and Kuypers, 1978; Menetrey et al, 1985; Brockett et al, 2013)

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Summary

Introduction

The propriospinal system is comprised of spinal interneurons with longitudinal axonal projections that extend outside their segment of origin, forming a network that connects motor and sensory circuits throughout the length of the spinal cord (propriospinal neurons; PNs) This intraspinal network is important for the propagation of supraspinal signals (Cowley et al, 2008, 2010), interlimb coordination It has become increasingly important to define PNs by their developmental origin, which is based on early transcription factor expression (Goulding, 2009) These developmentally defined interneuron populations (i.e., V0-V3 and dI0-dI6) form anatomically and functionally discrete spinal neuron classes that are amenable to genetic targeting. The contribution of other developmentally defined interneuron classes has not been investigated across PN populations

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