Using behavioral biomarkers to redefine epochs of spontaneous recovery following spinal cord injury
Eisdorfer, J. T.; Thackray, J.; Theis, T.; Vivinetto, A.; Ricci, M. T.; Lin, S.; Oputa, O.; Martinez, A. M.; Nacht, H. D.; Tschang, M.; Mahmood, M.; Tucker, A.; Pusuloori, S.; Zmoyro, L.; Abraira Lab Computational Group, ; Popovich, P.; Ferguson, A. R.; McTigue, D.; Tysseling, V. M.; Dulin, J.; Hollis, E.; Datta, S. R.; Abraira, V. E. G.
Show abstract
The brain-spinal cord axis generates movement by assembling motor primitives into coordinated sequences. Spinal cord injury (SCI) disrupts this neuroaxis, impairing not only locomotion, but the full repertoire of behavior. Traditional scales for quantifying recovery collapse this complexity into predefined locomotor-focused criteria that obscure heterogeneity in recovery. To quantify the full behavioral repertoire following SCI, we adapted motion sequencing (MoSeq) to identify sub-second behavioral "syllables" and capture their usage and sequential organization without predefined features. We identified biomechanically distinct variants within syllable classes that are shared across injury severities and found that recovery is jointly structured by injury severity and individual mouse identity. Changes in sequences, however, unfold along a conserved temporal trajectory. By compressing behavior into a single metric, we uncovered clusters of coevolving locomotor and non-locomotor behaviors. These results frame SCI recovery with repertoire-level changes, where adaptive strategies emerge from constrained access to motor primitives and their sequences.
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