Adaptation after vastus lateralis denervation in rats demonstrates neural regulation of joint stresses and strains
- Northwestern University, United States
- Shirley Ryan AbilityLab, United States
Figures
Figure 1
Actions of quadriceps muscles on task performance variables and internal joint state variables, and possible adaptation strategies after VL paralysis.
The left schematic in (a) illustrates the anatomical organization of the quadriceps muscles; VI is indicated in gray because it is located underneath RF. The right schematics depict the force directions produced by each of these muscles on the patella (top), the corresponding joint torques (middle), and the mediolateral patellar forces produced by VM and VL (bottom). Note that RF produces torques at both the hip and knee, and produces negligible mediolateral force on the patella. VM and VL have redundant contributions to knee torque (task variables), and opposite contributions to mediolateral patellar forces (internal joint variables). Panel (b) illustrates alternate adaptation strategies for compensating to paralysis of VL. The left column shows the consequences of an adaptation strategy prioritizing regulation of task performance variables: increasing VM activation restores joint torques and therefore joint kinematics, but would create an unbalanced mediolateral force on the patella. The middle column shows the consequences of an adaptation strategy prioritizing regulation of internal joint state variables: increasing RF activation and reducing VM activation eliminates mediolateral forces on the patella, but would create aberrant joint torques at the hip. The right column shows the consequences of an adaptation strategy that considers both task performance and internal joint state, preferentially increasing RF to minimize mediolateral patellar forces while maintaining VM activation to limit deviations in joint torques.
Figure 2
Paralysis of VL by denervation.
Panel (a) illustrates EMGs from VL and tibialis anterior (TA) during treadmill locomotion in one rat before (base), immediately after (week 1), and several weeks after (week 7) VL denervation. The vertical dashed lines in each plot indicate the onset of TA activity, and the horizontal thick bars at the bottom indicate the stance phase. VL activity was largely abolished after nerve cut, while that of other muscles (indicated here by TA) persisted. The small residual activity in VL was likely due to motion artifact or low-level cross talk. The averaged EMG envelope of VL over many strides (95% confidence interval for the mean, Ns = 104, 102, 88 for base, week 1 and week 7 respectively) confirms this result (b). The mass of the denervated VL, measured 8 weeks after nerve cut, was significantly lower for all animals as compared to the mass of the intact VL in the contralateral hindlimb. Bars are averages ± standard deviations (s.d.) across animals; N = 6 for each bar (c). ***p<0.001.
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Figure 2—source data 1
Mass of denervated and intact VL.
- https://doi.org/10.7554/eLife.38215.005
Figure 3 with 1 supplement
Preferential increase of RF activation following VL paralysis.
Panel (a) illustrates locomotor activity in RF and VM before (base) and after (week 1, week 2 and week 7) VL denervation for one animal. Activation of TA is shown to indicate the onset of each gait cycle (dashed vertical lines), and the horizontal thick bars at the bottom indicate the stance phase of locomotion. In the first week after VL denervation, activity of both RF and VM increased. At later weeks, activity in VM reduced to levels similar to baseline, whereas activation of RF remained elevated. Panel (b) illustrates the EMG envelopes of RF, VM and TA in this same animal (95% confidence interval for the mean activity, Ns = 104, 102, 96, 88 strides for base, week 1, week 2, and week 7 respectively), and confirms the results shown in (a). The shaded region indicates the stance phase for the baseline condition. Panel (c) reports the integrated activity during stance of RF and VM before (base) and after VL paralysis (week 1, 2, 7) for all animals (averages ± s.d. across animals), expressed as a multiple of the integrated activity observed in baseline conditions. Note that RF activation was larger than VM activation at each week after VL paralysis. For RF: N = 5, 4, 5, and 3 animals contributed to the bars at base, week 1, week 2, and week 7, with an average number of strides of Ns = 65, 94, 64 and 99 respectively. Note that because of exclusion criteria (see Materials and methods), not every animal contributed data to each bar. For VM: N = 5, 4, 5, and 4 animals, and Ns = 74, 98, 53, 93 strides contributed to the same time points. Significance levels: **p<0.01; ***p<0.001.
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Figure 3—source data 1
Integrated activity of quadriceps muscles during stance phase of locomotion.
- https://doi.org/10.7554/eLife.38215.009
Figure 3—figure supplement 1
Activation of muscles with hip extension actions over the adaptation period.
Conventions are the same as in Figure 3. Panel (a) depicts the averaged EMG envelopes (Ns = 104, 102, 96, 88 strides for base, week 1, week 2 and week 7 respectively) from the same animal as shown in Figure 3. Activation of BFp and SM decreased initially after VL paralysis but recovered to activation levels similar to baseline after 7 weeks. Activation of GRc remained lower than baseline even at 7 weeks after VL paralysis. Bars in (b) show average integrated activity related to the stance phase for each muscle, expressed as a multiple of the baseline values. Bars are averages ± s.d. across animals. BFp: pweek1 = 0.595, pweek2 <0.001, pweek7 = 1; N = 5, 4, 5, 4 animals contributed to base, week 1, week 2 and week 7, with an average number of strides of Ns = 70, 70, 48, 78 respectively. SM: pweek1 = 0.007, pweek2 = 0.491, pweek7 = 0.313; N = 4, 4, 4, 3 animals, and Ns = 79, 97, 73, 103 strides. GRc: pweek1 <0.001, pweek2 = 0.001, pweek7 = 0.001; N = 3, 3, 3, 2 animals, and Ns = 75, 97, 77, 89 strides.
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Figure 3—figure supplement 1—source data 1
Integrated activity of hip extensor muscles during stance phase of locomotion.
- https://doi.org/10.7554/eLife.38215.008
Figure 4
Quadriceps muscle masses measured 8 weeks after VL paralysis.
At the end of the experiment, we measured the mass of RF, VM and VI both in the hindlimb affected by VL denervation (ipsi), and in the contralateral limb (contra). There was a significant increase in the mass of the ipsilateral RF (p<0.05), and no significant difference in the mass of VM or VI. Bars are averages ± s.d. across animals; N = 6 for each bar.
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Figure 4—source data 1
Quadriceps muscle masses in the ipsilateral and the contralateral hindlimbs.
- https://doi.org/10.7554/eLife.38215.011
Figure 5
Adaptation of overall kinematics following VL paralysis.
Panel (a) illustrates the joint angle conventions used for these analyses. For each angle, smaller numbers indicate greater flexion (i.e. the gray angles in the figure are smaller for flexed angles). Panel (b) shows the joint angle trajectories at the hip, knee, and ankle during baseline (blue), week 1 (red), and week 7 (orange) after VL paralysis for one animal (hip and knee: Ns = 72, 31 and 50 strides for base, week 1 and week 7; ankle: Ns = 49, 13, 36). The bars at the top of each plot indicate the periods of stance phase for each time point of adaptation. Panel (c) reports the percentage of stance and the range of motion for each joint angle before and after VL paralysis for all animals (averages ± s.d. across animals). Stance percentage: N = 6, 4, 5, 5 animals for base, week 1, week 2 and week 7, and an average number of strides of Ns = 48, 41, 34, 59 respectively. Hip ROM: N = 5, 4, 4, 4 animals, and Ns = 58, 47, 50, 93 strides. Knee ROM: N = 6, 5, 4, 5 animals, and Ns = 64, 57, 50, 86 strides. Ankle ROM: N = 6, 4, 4, 5 animals and Ns = 59, 55, 44, 82 strides. **p<0.01; ***p<0.001.
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Figure 5—source data 1
Overall kinematic features before and after VL devervation.
- https://doi.org/10.7554/eLife.38215.013
Figure 6 with 1 supplement
Persistent deviations in hindlimb kinematics following VL paralysis.
Panel (a) illustrates limb configurations at the end of the stance phase at baseline (black), week 1 (red), week 2 (green), and week 7 (orange) after VL paralysis. For ease of comparison, thin black lines indicating the baseline limb configuration are overlaid on the limb configurations shown for weeks 1, 2, 7. Joint angles were averaged across animals and used to plot the configurations shown in the figure. Panel (b) shows the angles at the hip, knee, and ankle averaged across animals before and after VL paralysis (averages ± s.d. across animals). Hip: N = 5, 4, 4, 5 animals for base, week 1, week 2 and week 7, and an average number of strides of Ns = 54, 47, 44, 74 strides. Knee: N = 6, 5, 5, 5 animals, and Ns = 58, 51, 36, 74 strides. Ankle: N = 6, 4, 5, 5 animals, and Ns = 54, 51, 34, 73 strides. Panel (c) shows the global kinematic parameters limb angle and limb length averaged across animals before and after VL paralysis (averages ± s.d. across animals). Limb length: N = 6, 4, 5, 5 animals, and Ns = 59, 52, 34, 74 strides. Limb angle: N = 5, 3, 4, 5 animals, and Ns = 54, 48, 42, 74 strides. *p<0.05; **p<0.01; ***p<0.001.
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Figure 6—source data 1
Joint kinematics and global limb kinematics at the end of the stance phase of locomotion.
- https://doi.org/10.7554/eLife.38215.017
Figure 6—figure supplement 1
Joint configurations measured at mid-stance.
Conventions are the same as in Figure 6. Panel (a) illustrates limb configurations at mid-stance at baseline (black), week 1 (red), week 2 (green), and week 7 (orange) after VL paralysis. Panel (b) shows the angles at the hip, knee, and ankle averaged across animals before and after VL paralysis (averages ± s.d. across animals). Hip: pweek1 = 1, pweek2 = 0.027, pweek7 = 0.011; N = 5, 5, 4, 5 animals for base, week 1, week 2 and week 7, and an average number of strides of Ns = 53, 42, 44, 74 strides. Knee: pweek1 <0.001, pweek2 = 0.395, pweek7 = 0.140; N = 6, 5, 5, 5 animals, and Ns = 59, 50, 41, 74 strides. Ankle: pweek1 <0.001, pweek2 =< 0.001, pweek7 = 0.038; N = 6, 4, 5, 5 animals, and Ns = 55, 49, 39, 73 strides. Panel (c) shows the global kinematic parameters limb angle and limb length averaged across animals before and after VL paralysis (averages ± s.d. across animals). Limb length: pweek1 = 0.060, pweek2 = 1, pweek7 = 1; N = 6, 4, 5, 5 animals, and Ns = 59, 51, 40, 74 strides. Limb angle: pweek1 <0.001, pweek2 = 0.015, pweek7 = 1; N = 5, 4, 4, 5 animals, and Ns = 54, 41, 42, 74 strides. *p<0.05; **p<0.01; ***p<0.001.
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Figure 6—figure supplement 1—source data 1
Joint kinematics and global limb kinematics in the middle of the stance phase of locomotion.
- https://doi.org/10.7554/eLife.38215.016
Additional files
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Transparent reporting form
- https://doi.org/10.7554/eLife.38215.018
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Adaptation after vastus lateralis denervation in rats demonstrates neural regulation of joint stresses and strains
eLife 7:e38215.
https://doi.org/10.7554/eLife.38215
