Degradation of mouse locomotor pattern in the absence of proprioceptive sensory feedback

Abstract

Mammalian locomotor programs are thought to be directed by the actions of spinal interneuron circuits collectively referred to as "central pattern generators." The contribution of proprioceptive sensory feedback to the coordination of locomotor activity remains less clear. We have analyzed changes in mouse locomotor pattern under conditions in which proprioceptive feedback is attenuated genetically and biomechanically. We find that locomotor pattern degrades upon elimination of proprioceptive feedback from muscle spindles and Golgi tendon organs. The degradation of locomotor pattern is manifest as the loss of interjoint coordination and alternation of flexor and extensor muscles. Group Ia/II sensory feedback from muscle spindles has a predominant influence in patterning the activity of flexor muscles, whereas the redundant activities of group Ia/II and group Ib afferents appear to determine the pattern of extensor muscle firing. These findings establish a role for proprioceptive feedback in the control of fundamental aspects of mammalian locomotor behavior.

Keywords: locomotion; pattern generation; proprioception; sensory feedback.

Fig. 1.

EMG pattern during wild-type and Egr3 mutant walking. (A, i) Raw EMG data from flexor muscles during a walking sequence that includes three swing phases (shaded background) and two complete stance phases (white background) in wild-type (Left) and a Egr3 mutant (Right) mice. Blue arrows indicate the persisting activity in tibialis anterior (TA) muscle activity until the end of swing phase. (ii) Averaged flexor EMG activities triggered around swing offset (blue dashed lines). Bold red lines represent the pooled average recordings from all Egr3 mutant animals (N = 14 for Ip, 6 for St, and 14 for TA animals), and light thin red lines are averages from individual recordings. Bold black lines represent pooled average from all wild-type mice (N = 13 for Ip, 6 for St, and 16 for TA animals). Horizontal black (wild type) and red (Egr3 mutant) bars on Top indicates the average duration (+SD) of swing (sw) and stance (st) phases. (B and C) Histograms illustrating the delay of on- and offsets (Left and Right histograms, respectively) of St (B, 6 wild-type and 5 mutant animals) and TA (C, 13 wild-type and 10 mutant animals) activity relative to the Ip activity during walking. Black bars represent data from wild-type and open red bars from Egr3 mutant animals. (D, i) Two sets of raw EMG recordings, one showing Ip and GM activities (Top) and one showing Ip, VL, and Gs activities. (ii) Averaged extensor EMG activities triggered around swing offsets (blue dashed lines) (N = 3 for GM, 7 for VL, and 10 for Gs wild-type animals and 5 for GM, 5 for VL, and 10 for Gs mutant animals). Horizontal bars on Top of A, ii and B, ii indicate the average duration (+SD) of sw and st phases in wild-type (black bars) and in Egr3 mutant (red bars) mice.

Fig. 2.

Kinematic and functional consequences of the absence of early TA offset. (A) Average angular movement of three leg joints during walking of wild types (black lines, n = 16 animals) and Egr3 mutant mice (red lines, n = 18 animal). Bold lines are pooled averages from all mice and thin lines are averages from individual animals. Horizontal red bars on Top indicate the average duration (+SD) of swing (sw) and stance (st) phases, together with the similar data from wild types (black bars). (B) Comparison of mean (+SD) of maximal and minimal hip joint angles (Top graphs) and minimal joint angles of knee and ankle joints during swing phase (Bottom graphs). ***P < 0.001. (C and D) Stick reconstruction of swing phases on Top and toe trajectories of multiple steps overlapped with EMG events from two steps from a wild-type (C) and an Egr3 mutant (D) mouse. Sketches on the Bottom indicate the color-coded EMG events in Upper diagrams. Black and gray bars indicate flexor and extensor activity, respectively. The large rectangle in the background is the average step cycle, shaded area indicating the swing phase. (E) The Egr3 mutant mice make more errors during walking on a horizontal ladder, determined as more frequent foot droppings between rungs than in wild types. Each bar indicates number of steps that landed safely on a rung (black bars) or dropped between the rungs (red bars) counted during one run (N = 13 for wild type, 15 for mutant).

Fig. 3.

EMG pattern during wild-type and Egr3 mutant swimming. (A) Examples of EMG recordings from flexor muscles moving the hip (iliopsoas, Ip), knee (semitendinosus, St), and ankle (tibialis anterior, TA) during wild-type (Left) and Egr3 mutant (Right) mice swimming. (B and C) Histograms illustrating the delay of on- and offsets (Left and Right histograms, respectively) of St (B, 6 wild-type and 3 mutant animals) and TA (C, 11 wild-type and 10 mutant animals) muscle relative to the activity of on- and offsets of the Ip muscle during wild-type (black bars) Egr3 mutant (red bars) swimming. (D) Two examples of EMG recordings the hip flexor Ip and the most proximal extensor, the gluteus maximus (GM) on the Top and the Ip and two extensors for knee (vastus lateralis, VL) and ankle (gastrocnemius, Gs) during wild-type (Left) and Egr3 mutant (Right) mice swimming. Green arrows indicate rhythmic off periods of Gs activity during Egr3 mutant swimming.

Fig. 4.

Flexors are synchronous in a mice line that lacks all proprioceptors. An example of the EMG patterns of three flexors moving three joints and the ankle extensor Gs during swimming (A) and walking (B) of a Pv::cre; Isl2::DTA (P^kill) mouse.