Non-steady locomotion in mice: a translational project on stability and modular organisation
Human Cognitive and Systems Neuroscience
Final Report Abstract
The ability of vertebrates to sense the position of body parts in space is called proprioception. Muscle spindles (group Ia/II sensory afferents) and Golgi tendon organs (group Ib) are two classes of proprioceptors that can provide to the central nervous system information about the length of a stretched muscle and the tension developed during contraction. While we now know that the ablation of these receptors in mice can lead to devastating disruptions to locomotion, the extent to which proprioception is needed for the generation and control of locomotion is still unclear. Proprioceptive afferent fibres enter the spinal cord through the dorsal roots and synapse with both spinal and supraspinal centres, ultimately relaying information to the cerebellum and sensory cortex through the dorsal column-medial lemniscus pathway. Here, we used a combination of mouse genetics, lesion models and computational neuroscience to investigate which local and supraspinal proprioceptive pathways are involved in the control of locomotion and to what degree they contribute to safe, stable walking. By means of a custom-built treadmill, we administered randomly timed perturbations during locomotion that consisted in sudden accelerations or abrupt mediolateral displacements of the belt. Electromyographic activity of hindlimb muscles was recorded from: i) wild type mice before and after surgical deafferentation of the dorsal column-medial lemniscus pathway, ii) Egr3-/- mice, in which muscle spindles regress immediately after birth, and iii) PVCre::AviliDTR mice, in which both muscle spindles and Golgi tendon organs can be acutely ablated by systemic injection of diphtheria toxin. Synergistic muscle activation patterns were extracted via non-negative matrix factorisation. We investigated how the motor modules (or time-invariant muscle weightings) were distributed in normal and perturbed locomotion. Subsequently, we examined the motor primitives (or time-dependent synergistic coefficients) by calculating their duration, time of activation and Hurst exponent, a nonlinear metric derived from fractal analysis. Despite no changes in the number of muscle synergies needed for normal and perturbed locomotion in all groups, we found evidence for a supraspinal integration of proprioceptive information when animals coped with perturbations. Wild type mice could produce a temporal modulation of motor primitives in perturbed conditions that the Egr3-/- mice did not display. After systemic injection of diphtheria toxin, also the PVcre::AdviDTR mice lost the ability to modulate muscle activity with patterns resembling, even in unperturbed conditions, those of pre-injection perturbed walking. Interestingly, after spinal lesion, wild-type too failed to modulate motor output. These mice not only produced at all times locomotor patterns similar to those of pre-lesion unperturbed walking, but lost as well the skill to cope with perturbations, stopping on the treadmill every time an acceleration and/or a mediolateral displacement were administered. Our data-driven findings unmistakably show that the involvement of supraspinal centres is not only important for smoothly dealing with perturbed locomotion, but even fundamental when spinal pathways are intact and free to integrate proprioceptive sensory information.
Publications
- Modular organization of murine locomotor pattern in the presence and absence of sensory feedback from muscle spindles. J Physiol 597: 3147–3165, 2019
Santuz A, Akay T, Mayer WP, Wells TL, Schroll A, Arampatzis A
(See online at https://doi.org/10.1113/JP277515) - Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them. J Neurophysiol 124: 1083–1091, 2020
Santuz A, Akay T
(See online at https://doi.org/10.1152/jn.00360.2020) - Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region. bioRxiv, 2020
van der Zouwen CI, Boutin J, Fougère M, Flaive A, Vivancos M, Santuz A, Akay T, Sarret P, Ryczko D
(See online at https://doi.org/10.1101/2020.11.30.404525) - Modulation of muscle synergies via supraspinal proprioceptive pathways. In: ISEK International Society of Electrophysiology and Kinesiology XXIII. Nagoya: 2020, p. 52
Santuz A, Laflamme O, Ross B, Brüll L, Arampatzis A, Akay T
