Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans

Jesper Lundbye-Jensen, Jens Bo Nielsen, Jesper Lundbye-Jensen, Jens Bo Nielsen

Abstract

Neural plasticity occurs throughout adult life in response to maturation, use and disuse. Recent studies have documented that H-reflex amplitudes increase following a period of immobilization. To elucidate the mechanisms contributing to the increase in H-reflex size following immobilization we immobilized the left foot and ankle joint for 2 weeks in 12 able-bodied subjects. Disynaptic reciprocal inhibition of soleus (SOL) motoneurons and presynaptic control of SOL group Ia afferents was measured before and after the immobilization as well as following 2 weeks of recovery. Following immobilization, maximal voluntary plantar- and dorsiflexion torque (MVC) was significantly reduced and the maximal SOL H-reflex amplitude increased with no changes in the maximal compound motor response (M(max)). Decreased presynaptic inhibition of the Ia afferents probably contributed to the increase of the H-reflex size, since we observed a significant decrease in the long-latency depression of the SOL H-reflex evoked by peroneal nerve stimulation (D2 inhibition) and an increase in the size of the monosynaptic Ia facilitation of the SOL H-reflex evoked by femoral nerve stimulation. These two measures provide independent evidence of changes in presynaptic inhibition of SOL Ia afferents and taken together suggest that GABAergic presynaptic inhibition of the SOL Ia afferents is decreased following 2 weeks of immobilization. The depression of the SOL H-reflex when evoked at intervals shorter than 10 s (homosynaptic post-activation depression) also decreased following immobilization, suggesting that the activity-dependent regulation of transmitter release from the afferents was also affected by immobilization. We observed no significant changes in disynaptic reciprocal Ia inhibition. Two weeks after cast removal measurements returned to pre-immobilization levels. Together, these observations suggest that disuse causes plastic changes in spinal interneuronal circuitries responsible for presynaptic control of sensory input to the spinal cord. This may be of significance for the motor disabilities seen following immobilization as well as the development of spasticity following central motor lesions.

Figures

Figure 1. Spinal mechanisms
Figure 1. Spinal mechanisms
During the experiments, EMG was obtained from SOL and TA muscles. Peripheral nerve electrical stimulation was delivered to the posterior tibial nerve (PTN), the common peroneal nerve (CPN) and the femoral nerve (FN) in order to investigate disynaptic reciprocal inhibition, ‘classical’ presynaptic inhibition and post-activation depression.
Figure 5. Presynaptic inhibition estimated from SOL…
Figure 5. Presynaptic inhibition estimated from SOL H-reflex facilitation by conditioning stimulation of the femoral nerve (FN)
The soleus H-reflex was facilitated by a heteronymous Ia volley from quadriceps and the amount of reflex facilitation was used to estimate the size of the conditioning Ia excitatory postsynaptic potential (EPSP). The upper panel illustrates the time course (at rest) of the effect of conditioning femoral nerve (FN) stimulation (single 1 ms) stimuli applied to the FN at the femoral triangle at 1.5 × MT on the size of the soleus test H-reflex. Size of the unconditioned soleus H-reflex 20–25% of Mmax. Conditioning test intervals were –8 to –3 ms. The abscissa shows the interval in ms between the conditioning stimulus and the test stimulus. The ordinate shows the size of the conditioned test reflex expressed in percentage of the test reflex. The time course was obtained before immobilization (pre-test 1, light grey; and pre-test 2, dark grey) after immobilization (post-test, black) and 2 weeks after cast removal (re-test, white). Based on the onset of facilitation a detailed time course in steps of 0.2 ms was obtained for each subjects in each test. The bottom panel illustrates this facilitation at best individual conditioning test intervals before, after and 2 weeks after immobilization. All depicted values are group average ±s.d.* denotes P ≤ 0.05.
Figure 2. Maximal voluntary contraction torque (MVC)…
Figure 2. Maximal voluntary contraction torque (MVC) was measured during ankle joint plantar flexion and dorsiflexion
Measures of maximal isometric muscle strength (MVC) before immobilization (grey bars), after immobilization (black bars) and after 1 week of recovery (white bars). The figure illustrates group mean peak torque (Nm) ±s.d. for plantar flexion and dorsiflexion. * denotes P ≤ 0.05, *** denotes P < 0.001
Figure 3. Hoffmann reflex and M-wave recruitment…
Figure 3. Hoffmann reflex and M-wave recruitment curves, and Hmax/Mmax ratios
Hoffmann reflexes were elicited in SOL before (grey), after (black) and 2 weeks after immobilization (white). The upper panel illustrates Hoffmann reflex (circles) and M-wave (squares) recruitment curves for a representative subject. The abscissa represents the stimulation intensity normalized to the M-wave threshold in pre-test 1, the ordinate illustrates response amplitude normalized to the corresponding Mmax. The lower panel illustrates group average Hmax/Mmax ratios (±s.d.) before (pre1 and pre2), after (cast removal) and 2 weeks after (re-test) immobilization. * denotes P ≤ 0.05.
Figure 4. Measurement of disynaptic reciprocal inhibition…
Figure 4. Measurement of disynaptic reciprocal inhibition from ankle dorsiflexors to ankle plantar flexors by the H-reflex technique at rest
The time course (at rest) of the effect of conditioning peroneal nerve stimulation (single 1 ms) stimuli applied to the peroneal nerve 2–3 cm distal to the caput fibulae at 1.1 × MT on the size of the soleus test H-reflex. (This was evoked by single 1 ms stimuli applied to the tibial nerve in the popliteal fossa. Size of the unconditioned soleus H-reflex 20–25% of Mmax.) The abscissa shows the interval in ms between the conditioning stimulus and the test stimulus. The ordinate shows the size of the conditioned test reflex expressed in percentage of the test reflex. The time course was obtained before immobilization (pre-test 1, light grey; and pre-test 2, dark grey) after immobilization (post-test, black) and 2 weeks after cast removal (re-test, white). The short-latency, presumed disynaptic, reciprocal inhibition was seen at conditioning-test (CT) intervals between 2 and 4 ms. It was expressed as the size of the conditioned H-reflex as a percentage of the control H-reflex size. The figure illustrates group average ±s.d.
Figure 6. D2 inhibition
Figure 6. D2 inhibition
Time course of the long-latency depression of the SOL H-reflex (D2 inhibition) evoked at 40–100 ms conditioning-test interval by conditioning peroneal nerve stimulation (single 1 ms) stimuli applied to the peroneal nerve 2–3 cm distal to the caput fibulae at 1.1 × MT. The abscissa shows the interval in ms between the conditioning stimulus and the test stimulus. The ordinate shows the size of the conditioned test reflex expressed in percentage of the test reflex. The time course was obtained before immobilization (pre-test 1, light grey; and pre-test 2, dark grey) after immobilization (post-test, black) and 2 weeks after cast removal (re-test, white). All depicted values are group average ±s.d.* denotes P ≤ 0.05.
Figure 7. Post-activation depression
Figure 7. Post-activation depression
The figure illustrates the frequency-related depression of the SOL H-reflex at interstimulus intervals of 1 s relative to 10 s. In A, the ordinate shows the average amplitude of the SOL H-reflex obtained at 1 s ISI in percentage of the average SOL H-reflex amplitude obtained at 10 s ISI. In B, the ordinate shows the amount of the frequency-related (post-activation) depression from the control reflex obtained at 10 s ISI. The data were obtained before immobilization (pre-test 1, light grey; and pre-test 2, dark grey) after immobilization (post-test, black) and 2 weeks after cast removal (re-test, white). All depicted values are group average ± s.d.* denotes P ≤ 0.05.

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