Spinal Control of Locomotion: Individual Neurons, Their Circuits and Functions

Abstract

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle activation profiles are observed during locomotion across species. This difference may potentially be driven by a modified distribution of muscle afferents at multiple segmental levels in humans, resulting in an altered interaction between different classes of spinal interneurons. Further, different classes of spinal interneurons are likely activated or silent to some extent simultaneously in all species. Regardless of these limitations, continuous efforts on the function of spinal interneuronal circuits during mammalian locomotion will assist in delineating the neural mechanisms underlying locomotor control, and help develop novel targeted rehabilitation strategies in cases of impaired bipedal gait in humans. These rehabilitation strategies will include activity-based therapies and targeted neuromodulation of spinal interneuronal circuits via repetitive stimulation delivered to the brain and/or spinal cord.

Intensive Functional Neurorehabilitation and Follow-up of 84 Paraplegic Dogs Affected by Intervertebral Disc Disease

“…Evidence of FNRIP e cacy has been reported by various studies (Côté et al, 2018). Such ndings indicate that multidisciplinary protocols can enable neural reorganization associated with synaptogenesis, and support the introduction of locomotor training as a primary rehabilitation modality (Lavrov et al, 2006;Martins, 2015;Mehrholz et al, 2012Mehrholz et al, , 2017.…”

Somatosensory corticospinal tract axons sprout within the cervical cord following a dorsal root/dorsal column spinal injury in the rat

“…In normal rats, as in primates, S1 CST terminals synapse in the (contralateral) dorsal horn primarily on to the presumed axons/dendrites of intraspinal neuronal populations (Côté, Murray, & Knikou, ; Gosgnach et al, ; Schieber, ; Ziskind‐Conhaim & Hochman, ). Target neurons may include local reflex, long and short range propriospinal (Filli & Schwab, ) and commissural interneuronal populations (Bannatyne, Edgley, Hammar, Jankowska, & Maxwell, ; Jankowska et al, ; Soteropoulos, Edgley, & Baker, ), which in turn connect with motor neurons, and/or regulate (or gate) ascending tracts (i.e., the dorsal columns, spinocerebellar and spinothalamic pathways).…”

Newly regenerated axons through a cell-containing biomaterial scaffold promote reorganization of spinal circuitry and restoration of motor functions with epidural electrical stimulation

“…Greater synaptophysin co-localization with motor neuron and interneuron in animals treated with combined therapy suggests that regenerating axons form functional connections with sub-lesional circuitry facilitating reorganization with EES-enabled training. Plasticity below the SCI has been attributed to rehabilitation 43,44 , while the quality of movement is largerly depends on descending commands and sensory feedback integration on different interneuronal populations 11,17,[45][46][47][48] . Although the numbers of rats are relatively small, the concordance of behavioral, electrophysiological and histological results convincingly demonstrate that greater synaptic reorganization on the interneurons in the presence of regenerated axons leads to improvements in polysynaptic responses, improving gait, particularly in group with combined treatment.…”