Operant conditioning of H-reflex can correct a locomotor abnormality after spinal cord injury in rats

Abstract

This study asked whether operant conditioning of the H-reflex can modify locomotion in spinal cord-injured rats. Midthoracic transection of the right lateral column of the spinal cord produced a persistent asymmetry in the muscle activity underlying treadmill locomotion. The rats were then either exposed or not exposed to an H-reflex up-conditioning protocol that greatly increased right soleus motoneuron response to primary afferent input, and locomotion was reevaluated. H-reflex up-conditioning increased the right soleus burst and corrected the locomotor asymmetry. In contrast, the locomotor asymmetry persisted in the control rats. These results suggest that appropriately selected reflex conditioning protocols might improve function in people with partial spinal cord injuries. Such protocols might be especially useful when significant regeneration becomes possible and precise methods for reeducating the regenerated spinal cord neurons and synapses are needed for restoring effective function.

Figure 1.

A, Experimental sequence. After learning to walk on the treadmill, each rat was implanted with soleus EMG electrodes and nerve-cuff stimulating electrodes. Several weeks later, it was subjected to an LC transection. After the BBB score (Basso et al., 1995) had returned to 20–21, the first treadmill session assessed locomotion and locomotor H-reflexes. Then, the rats were (HRup rats) or were not (control rats) exposed to the HRup conditioning protocol. Finally, the second treadmill session reassessed locomotion and locomotor H-reflexes. B, Camera lucida drawings of transverse sections of T8–T9 spinal cord. Left, A normal rat with LC, dorsal column CST, dorsal column ascending tract (DA), and ventral column (VC) labeled. Right, An LC-transected rat. In the LC rat, the section shown is at the lesion epicenter. Hatching indicates gray matter, and stippled areas are the main corticospinal tract. Scale bar, 1 mm. Most of the right LC is gone.

Figure 2.

Effects of H-reflex up-conditioning on locomotor H-reflexes and soleus locomotor bursts. A, Average ± SEM locomotor H-reflexes and left and right soleus burst amplitudes, widths, and durations for control rats (open bars) and HRup rats (solid bars) for the second treadmill session as percentage of their values for the first (i.e., initial) session. Asterisks indicate significant changes from the first to the second session (*p < 0.05; **p < 0.01). Locomotor H-reflexes and right soleus burst amplitudes and widths are increased in the HRup rats. The control rats show no significant change. B, The main traces are average right soleus bursts and the inset small traces are average stance H-reflexes from a control rat and an HRup rat for the first (solid) and second (dotted) treadmill sessions. [For the H-reflexes shown, average background EMG and M-response size were the same for the first and second sessions (for methods, see Chen et al., 2005).] Calibration: horizontal bars, 2 ms for both the control and HRup rats; vertical bars, 50 and 200 μV, respectively. The fine horizontal lines in the bottom graph indicate burst half-width (i.e., the width at half the peak value). (Half-width is shown here only for illustrative purposes. Materials and Methods describes the more comprehensive measure used to assess the effects of conditioning on burst width.) In the second session, the stance H-reflex and the right soleus burst amplitude and half-width are increased in the HRup rat. The control rat shows no change in the H-reflex or in the burst.

Figure 3.

Effects of H-reflex up-conditioning on the step-cycle. A, Average ± SEM step-cycle duration and RBO–LBO duration (time from right soleus burst onset to left soleus burst onset) for control rats (open bars) and HRup rats (solid bars) for the second treadmill session as percentage of their values for the first (i.e., initial) session. **p < 0.01, significant change from the first to the second session. Step-cycle duration is unchanged in both control and HRup rats. RBO–LBO duration (which was lower than normal in the first treadmill session; see Results) is increased in HRup rats only. B, Right and left soleus bursts (rectified EMG) from an HRup rat for the first (i.e., before up-conditioning) treadmill session and the second (i.e., after up-conditioning) session. Calibration: horizontal bar, 0.5 s; vertical bar, 100 and 150 μV for the right and left bursts, respectively. Each RBO (●) or LBO (○) is marked. The short vertical dashed lines mark the midpoints between RBOs (i.e., the midpoints of the step-cycles), which is the time when LBOs should occur (as in normal rats). Before H-reflex up-conditioning, LBO occurs too early; after up-conditioning, it occurs on time.