The Role of Muscle Spindle Feedback in the Guidance of Hindlimb Movement by the Ipsilateral Forelimb during Locomotion in Mice

The well organized swing movement in mice requires proprioceptive sensory feedback from the muscle spindles. A, Trajectories of the hindlimb paw of wild-type mice (left) are very stereotyped across animals, whereas more variability in movement is observed in Egr3-KO mice (right). The colored lines are swings from an individual animal, and the bold black line is the pooled average. The average posterior paw position at swing onset and the anterior paw position at swing offset are illustrated as open and closed circles, respectively. B, Histogram representing the distribution of hindlimb paw positions relative to the hip joint at the end of hindlimb swing movement (HL_AP) in wild-type (left) and Egr3-KO (right) mice. C, Histogram showing the distribution of forelimb paw positions relative to hip joint at the end of forelimb stance movement (FL_PP) in wild-type (left) and Egr3-KO (right) mice. D, Histogram presenting the distribution of the distance between HL_AP and FL_PP in wild-type (left) and Egr3-KO (right) mice. E, Diagram illustrating the relationship between the average (±SD) of the HL_AP and FL_PP in wild-type (left) and Egr3-KO (right) mice during unperturbed hindlimb swing movements.

Induction of a stumbling corrective reaction is independent of proprioceptive sensory feedback from the muscle spindles. A, Hip, knee, and ankle joint angles, relative toe x- and y-coordinates (toe height) synchronized with raw EMG activity of flexor (Ip, St, TA) and extensor (VL, Gs) muscles. Electrical stimulation of the saphenous nerve during swing phase is indicated by the darker gray region inside the third swing phase. Green arrows point to the activity of the flexor muscle elicited by the stimulation. Stick diagram reconstruction of a swing phase before SCR (i), an SCR (ii), and a swing phase after SCR (iii) are illustrated below. B, Trajectories of the hindlimb paw during SCR are very stereotyped in wild-type animals (top) but are disorganized in Egr3-KO mice (bottom). The colored lines are individual swings, and the bold line is the pooled average from one animal. The average posterior paw position at swing onset and the anterior paw position at swing offset are illustrated as open and closed circles, respectively. The point of nerve stimulation is indicated by the gray circle. C, Changes in control swing and SCR durations (p = 0.016) and distances between the paw position from liftoff to touchdown (swing amplitude) in SCR events in wild-type mice (p < 0.001). No changes were observed in swing duration (p = 0.074) and swing amplitude (p = 0.534) during SCR events in Egr3-KO mice.

Limb movement during SCR remains well organized in wild-type mice but is more variable in the absence of proprioceptive sensory feedback from the muscle spindles. A, Histogram representing the distribution of HL_AP during SCR in wild-type (left) and Egr3-KO (right) mice. B, Histogram showing the distribution of FL_PP during the SCRs in wild-type (left) and Egr3-KO (right) mice. C, Histogram presenting the distribution of the distance between the HL_AP and FL_PP during SCRs in wild-type (left) and Egr3-KO (right) mice. D, Diagram illustrating the relationship between the average (±SD) of the HL_AP and FL_PP during normal swing movements (norm) and SCRs in wild-type (left) and Egr3-KO (right) mice during SCRs. ***p < 0.001. Histograms illustrating the distribution of FL_PP during SCR in individual WT and Egr3-KO mice are shown in Extended Data Figure 4-1.

The swing movement during cautious locomotion is well organized in wild-type mice but is more variable in the absence of proprioceptive sensory feedback from the muscle spindles. A, Histogram representing the distribution of HL_AP in swing movements during cautious locomotion in wild-type (left) and Egr3-KO (right) mice. B, Histogram showing the distribution of FL_PP in swing movements during cautious locomotion in wild-type (left) and Egr3-KO (right) mice. C, Histogram showing the distribution of the distance between the HL_AP and FL_PP in swing movements during cautious locomotion in wild-type (left) and Egr3-KO (right) mice. D, Diagram illustrating the relationship between the average (±SD) of the HL_AP and FL_PP during normal swing movements (norm) and swing movements during cautious locomotion (caut) in wild-type (left) and Egr3-KO (right) mice during SCRs. **p < 0.01, ***p < 0.001. Histograms illustrating the distribution of FL_PP during cautious locomotion in individual WT and Egr3-KO mice are shown in Extended Data Figure 5-1.