Distinguishing subtypes of spinal locomotor neurons to inform circuit function and dysfunction

Abstract

Locomotion is a complex motor task executed by spinal neurons. Given the diversity of spinal cord neurons, linking neuronal cell type to function is a challenge. Molecular identification of broad spinal interneuronal classes provided a great advance. Recent studies have used other classifiers, including location, electrophysiological properties, and connectivity, in addition to gene profiling, to narrow the acuity with which groups of neurons can be related to specific functions. However, there are also functional populations without a clear identifier, as exemplified by rhythm generating neurons. Other considerations, including experience or plasticity, add a layer of complexity to the definition of functional subpopulations of spinal neurons, but spinal cord injury may provide insight.

Keywords: Central pattern generator; Interneuron; Locomotion; Rhythm generation; Spinal cord injury.

Figure 1.. Subdivisions of cardinal class neurons.

(a)-(d), left. Representative spinal cord sections with the small symbols indicating the approximated locations of single neurons and schematics highlighting the input and output of the class of neurons as described in the text. Dotted arrows denote ascending or descending axons. Arrows represent excitatory synapses and lines represent inhibitor synapses. (a)-(d), middle. Classifiers used to subdivide cardinal class neurons. Black arrows indicate correlations or associations between classifiers. Dashed lines indicate indirect associations. Text without arrows indicates a classifier that has been used to subdivide the population but that is not currently associated with other classifiers. Red text is the entry point used in the text section. Green arrow in (c) applies only to Renshaw cells and Ia interneurons. Blue in (d) indicates what has been shown for the overlapping Shox2 population but not for all V2a neurons. Light gray indicates classifiers that have not been examined or that have not been associated with others to date. (a)-(d), right. Functional roles demonstrated or proposed for each subpopulation depicted. (e) Differences in the rostral-caudal distributions of subgroupings of V1 and V2a neurons. See text for references.

Figure 2.. Potential populations involved in locomotor rhythm generation.

(a) Shox2 neurons, (b) Hb9 neurons, and (c) VSCT neurons, location and connectivity as in Figure 1. In (b), light pink represents the type 2 Hb9 neurons [75] which are GFP positive in Hb9GFP mice but do not express Hb9 protein postnatally. (d) Populations in (a)-(c) together with the area with the first activated neurons following hindbrain stimulation in [56] shown in dark gray. The approximate localization of neurons active at increasing speeds of locomotion in [57] are shown in shades of brown, where the darkest is the highest speed. (e) Demonstrated and proposed roles of each potential rhythm generating population based on in vitro isolated cord experiments and in vivo experiments in adult. See text for references.

Figure 3.. Commonalities of subpopulations with new roles in locomotor circuitry after SCI.

(a) All 4 of the classes have a subpopulation with a rather common connectivity profile. A subpopulation of each class receives sensory afferent input, projects to motor neurons (ipsilateral in most cases), and is either interconnected to or a part of the central pattern generator (CPG). (b) Table highlighting the commonalities and the distinctions in connectivity and function. See text for references.