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Increased inhibitory effects on close synergists during muscle fatigue in the decerebrate cat
Braht Research. 4411(1988) 199-203
199
Elsevier BRE 22714
Increased inhibitory effects on close synergists during muscle fatigue in the decerebrate cat L. Hayward !, D. Breitbach 2 and W.Z. Rymer 1"3 t Department o f Physiology and :Graduate Program in Neuroscience. Northwestern University and ~Vetermts Administraiion Lakeside Medical Center. Chicago. IL 60611 (U.S.A. J
(Accepted 13 Octobcr 1987) Key words: Muscle fatigue: Reflex inhibition; Synergist: Muscle afferent
We compared the magnitude of reflex inhibition induced in the sol:us muscle by contraction or stretch of the medial gaslrocncmius (MG). before, during, and after electrically induced fatigue of the MG. Our findings are that MG fatigue is accompanied by "lsubstantial increase in solcus inhibition, which then recovers with MG rest. This increased inhibition may explain, at least in part. the dcclinc in motoneuron discharge rate that has been described in fatiguing human muscle.
Investigations of human subjects during maximum voluntary contractions of several different muscles have demonstrated that m o t o r unit discharge rate declines as muscle fatigues -'t2. This rate reduction parallels a slowing in muscle contractile speed, which results, in turn, in a reduction in fusion frequency of motor units It appears that this motor unit rate reduction serves to optimize force generation in fatiguing muscle, by matching neural input to changing muscle contractile p r o p e r t i e ¢ . At the present time the mechanism underlying this neural rate modulation is not fully understood. Some of the decline in m o t o r unit discharge rate may reflect rate adaptation of the m o t o n e u r o n 9"~°. Alternatively, recent investigations by Bigland-Ritchie et al. 3 have suggested a role for a peripheral feedback mechanism. These investigators demonstrated that the motor unit discharge rate, which normally recovers within 3 rain following fatiguing contractions of human muscles, does not recover if the muscle is kept ischemic, despite ample time for motoneuron recovery from the rate-adapted state. These authors propc, sed that these effects are most likely mediated by the reflex actions of the groups III and IV muscle afferents, afferents connected to receptors
that are known to be sensitive to the types of thermal and metabolic stimuli that arise during muscle fatigue ~H3. The present study was undertaken to assess the characteristics of this hypothetical fatigue-related peripheral feedback mechanism. In an animal model, we have examined the effects of fatigue of medial gastrocnemius on the reflex excitability of a non-fatigued synergist (sol:us) known to share many common afferent inputs with medial gastrocnemius ~. Preliminary results have been presented in abstract form s . In 14 decerebrate cats, medial gastrocnemius (MG) and soleus (SOL) were dissected free from the adjacent muscles and severed from their calcaneai attachments. The sural, common peroneal, and tibiai nerves were cut and a hip denervation was also performed. In the main experiments, the nerve to MG was isolated but left intact to allow selective electrical stimulation of the M G muscle. In 5 additional experiments, the M G m u s c l e - n e r v e was sectioned and stimulated proximally (see below). The tendon of SOL was attached to a non-compliant load ceil, and the MG tendon was attached to a similar but separate load cell m o u n t e d in-series with an electromagnetic
Correspondence: W.Z. Rymer, Department of Physiology. Ward 5-295, Northwestern University Medical School. 3113East Chicago
Avenue, Ch!cago, IL 60611. U.S.A. 0006-8993/88/$(13.5(tO 1988 Elsevier Science Publishers B.V. (Biomedical Division)
200 puller. The initial muscle lengths of both SOL and MG were set between 5 and 15 mm less than maximum physiological length. The electromyograms (EMG) of MG and SOL were recorded differentially with pairs of 75-1tm Teflon-coated stainless-steel wires inserted into the muscle bellies. The signals were amplified 100x, band pass filtered over 10-100 Hz, and full-wave rectified, All data (force, EMG and length) were sampled on-line by a PDP 11/73 computer at 5-ms intervals and stored on hard discs for later analysis. Force and EMG activity from MG and SOL were monitored before, during and after selective fatigue of MG. For each trial, an initial isometric SOL force between 5 and 9 N was established by applying mechanical pressure on the contralateral foot, or by torsion of the contralateral ankle and knee, thereby activating the crossed extension reflex ~6. Initial MG force was less influenced by the crossed extension reflex, never exceeding 3.0 N active force. SOL force was then recorded during varying increases in MG force elicited by either different amplitude ramp and hold stretches of MG or by a 3-s period of electrical stimulation of the MG muscle nerve, The ramp stretches of MG were 0.5 s in duration and of an amplitude ranging between 2 and 8 mm. Electrical stimulation of the MG nerve was applied at 1.3 times group I threshold, at frequencies between 20 and 50 Hz. Five to 10 trials of each stretch amplitude and stimulation frequency were recorded both before and after fatigue of MG. Fatigue of MG was elicited by electrical stimulation of its muscle nerve at 1.3 times group I threshold (1.3 × T) and 25 pulses/s, with duty cycles ranging from 3 to ! up to 7 to 1 (ratio of electrical stimulation to rest duration). MG was regarded as being fatigued if force output during tetanic stimulation had dropped to 30% or less of the original value. Following the completion of the fatigue protocol, we immediately resumed sampling force output of SOL and MG in response to the electrical stimulation and ramp strctch protocols outlined above. Post-fatigue measurements were obtained 30-50 rain following the cessation of the fatiguing stimulus. Fig. 1 shows the force responses of SOL and MG to electrical stimulation of the MG nerve (Fig. 1A) and ramp stretch of MG (Fig. 1B), respectively. Before fatigue (thin line), the MG force increase (upper
traces) evoked by either electrical stimulation or stretch is accompanied by a reflexly mediated decrease in SOL force (lower traces). Immediately after fatigue of I~G, force increases comparable to those produced before fatigue evoked much larger reductions in SOL force (see Fig. l, thick lines). Following recovery from MG fatigue, reflex inhibition of the SOL returned to values similar to those evoked before fatigue. To quantify the relations between reflex inhibition of SOL and MG force increase, we calculated the difference between the initial and stimulation-related output for each muscle using two specified time 'windows', placed immediately before and during isometric or stretch stimulation of MG (see filled time windows in Fig. l). This change in muscle force was used for analysis, instead of absolute force, to minimize the influence of crossed extensor related variability of initial muscle force. The initial force range for MG was 0.2-2.9 N and 5-9 N for SOL. The change in SOL force was plotted as a function of the corresponding increment in MG force Fig. 2 (part A, open boxes) shows the responses recorded from a typical non-fatigued preparation, in which the decrement in SOL force increased with increasing stretch-evoked MG force (illustrated by positive slope values). Fig. 2A (filled boxes) shows that the effect of fatigue was to increase the slope of the relation between MG force increment and SOL force reduction, and presumably the sensitivity of the heteronymous inhibitory pathways. A similar increase in the slopes of the regression lines during fatigue occurred in all seven experiments of this type. During stretch stimulation of MG (three experiments), MG fatigue was accompanied by an increase in mean slope of the M G - S O L regression from 0.07 to 0.21 (Newton decrement SOL/Newton increment MG). Slopes were estimated by least squares, forcing the linear regression through the origin. For these 3 preparations the percent increase in slope during fatigue was 176,532 and 645%. During electrical stimulation of MG (4 experiments) there was again an increase in mean slope from 0.35 to 0.78 during fatigue (Newtons decrement SOL/Newton increment MG). The percent increase in slope during fatigue within preparations was 137, 223, 295 and 441%. Because the scatter of data points was often fairly
201
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Fig. 1. Effect of MG fatigue on reflex responses in a non-fatigued synergist. SOL. A: the reflex inhibition the SOL (lower trace) elicited during isometric contraction of MG (upper trace), before (thin line) and during (thick line) selective fatigue of MG. Co:~traction of MG was evoked by electrical stimdlation of the MG muscle-nerve at 1.3 times a-threshold for 3 s ~stimulation frequency before fatigue was 40 Hz and 2(} Hz during fatigue). B: the reflex inhibition of SOL (lower trace) during a 6-mm ramp stretch of MG (upper trace), before (thin line) and during (thick line) fatigue of MG. The filled boxes indicate the time "windows" within which average force values for each strial were calculated.
large, summary comparisons of changes in reflex inhibition during fatigue were made primarily using m e a n SOL force reductions, calculated over a narrow band of MG forces. MG force ranges (for example see Fig. 2A) were chosen to include force increases common to all three conditions (before, during and after fatigue). Fig. 2B,C shows the mean decrements in SOL force before, during and after MG fatigue from the 7 experiments. During both isometric (Fig. 2B) and stretch stimulation (Fig. 2C) of MG, inhibition of SOL force increased by at least two-fold during fatigue as compared to before or after fatigue. In all 7 experiments evaluated using this procedure, tile mean decrement in SOL force was statistically greater during fatigue as compared to before and/or after fatigue (t-test, P < 0.01). These fatigue-induced changes in inhibition of the soleus could be mediated by either afferent haput from the fatiguing muscle, or from Renshaw neuron excitation by antidromic activation of motor axons during the fatiguing protocol. To evaluate the former possibility, in 5 experiments we sectioned the MG muscle nerve and electrically stimulated the proximal
end at various stimulus intensities for 3 s (similar to the test paradigm used to elicit reflex inhibition in SOL when the MG muscle-nerve was intact). At low stimulus intensities (within group I range, 1.1-1.5 x 7") and frequencies of 25-50 Hz, little or no effect on SOL force was recorded. At the same stimulus intensities but higher frequencies, 100-200 Hz, small decrements in SOL force production were recorded. However. more substantial reductions in SOL force, such as those seen during muscle fatigue, were recorded only at stimulus intensities at or above 10 x T, stimulus intensities appropriate for activating group !11 and IV afferent fibers 6. To assess the possible inhibitory contribution of antidromic activation of the motor axon during the fatiguing protocol, in one preparation the proximal end of the cut MG muscle-nerve was stimulated for 30 rain at intensities and rates equal to those used to fatigue the muscle (1.3 × T, 3 s, 25 Hz). This repetitive antidromic activation had no effect on ,he electrically mediated threshold of inhibition of SOL force (described above). Thus, the effects seen during fatigue were probably mediated by fatigue-related af-
202 B.
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Fig. 2. Comparisons of the decrement in SOL force elicited by MG force increase, before, during and after fatigue of MG. A: the decrement in SOL force, from a single preparation, plotted as a function of the MG force increase during ramp stretches (4-8 mm) before (I-q), during (B) and after (+) fatigue of MG. The slopes of the regression lines before, during and after fatigue were 0.(13, 0.18 and 0.10 (N SOL/N MG) respectively. Mean changes were determined by calculating the average force decrement in SOL evoked during MG stimulation, within a specified range of MG forces (see Force Window). The graphs in B and C illustrate tht mean decrements in SOL force for 7 preparations during isometric (B) and ramp (C) stimulation of MG. In these 7 experiments the mean decrement in SOL force was significantlygreater during fatigue of MG as compared to before or after fatigue (t-test, P < II.01).
ferent input from the muscle, not from antidromic activation of the motoneuron pool or prolonged excitation of Renshaw cells. Bigland-Ritchie et al. 3 have suggested that the decline of motor unit discharge rate during muscle fatigue may be reflexly mediated by excitation of the small diameter group III and IV afferents. Our reo suits are entirely consistent with this mechanism. Many group III and IV afferents are known to be very responsive to the type of mechanical, metabotic and thermal changes that may occur in muscle during fatigue ll'13. Thus, increases in group Ill and IV discharge during muscle fatigue may be responsible for increased inhibition of homonymous or heteronymous motoneurons, mediated presumably through inhibitory interneurons located in deeper lamina VII of the spinal cord 5. In contrast, it is unlikely that the large diameter
muscle spindle and Golgi tendon organ afferents are primarily responsible for mediating the fatigue-related reflex inhibition. Nelson and Hutton 14 have demonstrated that muscle spindle afferents do not change their response characteristics when the muscle is fatigued by electrical stimulus intensities within the group I range (although the possibility of F-mediated fatigue of intrafusal fibers has not been thoroughly examined). Golgi tendon organ receptor discharge, which is excited by increases in muscle force, would, if anything, be expected to show a relative decline during muscle fatigue tT, giving rise to a decrease in reflex Ib inhibition. One possible additional pathway through which group III and IV afferents may mediate feedback inhibition of motoneurons during fatigue is through increased excitation to the Renshaw cells. These recurrent inhibitory neurons are excited polysynaptically
203 by high threshold muscle afferents tS. Renshaw cell discharge is also contingent upon the discharge of the m o t o n e u r o n s , and Renshaw n e u r o n s , in turn, inhibit m o t o n e u r o n s , making t h e m possible modulators of m o t o n e u r o n discharge rate. T h e r e f o r e , it is possible that during muscle fatigue, increased group 111 and IV input m a y gradually facilitate the R e n s h a w - m e diated recurrent inhibitory p a t h w a y , resulting in progressive reduction of m o t o r unit discharge rate. Furt h e r m o r e , this reflex regulation would be appropriately d e p e n d e n t upon the changing metabolic and thermal state of the muscle, adjusting m o t o n e u r o n output to m a t c h the changing p r o p e r t i e s of the active muscle. Alternative!y, it ~s also k n o w n that the Ib in-
1 Baldissera, F., Hultborn, H. and Illert, M., Integration in spinal neuronal systems. In V.B. Brooks (Ed.), Handbook o.f Physiology. SectionJ. The Nervous S,vslem. Vol. 11, Motor Controt, Part 1, American Physiological Society, Bethesda, MD, 1981, pp. 505-595. 2 Bigland-Ritchie, B.R., Johansson, R.S., Lippoid, O.C.J. and Woods, J.J., Contractile speed and EMG changes during fatigue of sustained maximum voluntary contractions, J. Neurophysiol., 50 (1983) 313-324. 3 Bigland-Ritehie, B.R., Dawson, N.J., Johansson, R.S. and Lippold, O.C.J., Reflex origin for the slowing of motoneurone firing rates in fatigue of human voluntary contractions, J. Physiol. ( Lond. l, 378 (1986) 451-459. 4 Bigland-Ritchie, B.R. and Woods, J.J., Changes in musclc contractile properties and neural control during human muscular fatigue. Muscle Nerve, 7 (1984) 691-699. 5 Cleland, C., Rymer, W.Z. and Edwards. F., Force sensitive interneurons in the spinal cord of the cat. Science, 217 (1982) 652-655. 6 Eccles, R.M. and Lundberg, A., Synaptic actions in motoneurones by afferents which may evoke the flexion reflex, Arch. ital. Biol.. 97 (1959) 199-221. 7 Harrison, P.J. and Jankowska, E., Sources of input to interneurons mediating group I non-reciprocal inhibition of motoneurons in the cat, J. Physiol. (Lond.L 361 (1985) 379-401. 8 Hayward, L., Breitbach, D. and Rymer, W.Z., Increased inhibitory effects on close synerg~.stsduring muscle fatigue, Soc. Neurosci. Abstr., 13 (1987) 1532. 9 Kernell, D. and Monster, A.W., Time course and prop-
terneurons 7 and force sensitive interneurons 5 receive excitatory input f r o m the same groups of high threshold muscle afferents, raising the possibility that the gain of the lb and o t h e r inhibitory pathways m a y also be modulated during muscle fatigue. T h e results from o u r e x p e r i m e n t s simply confirm that there is an increase in h e t e r o n y m o u s reflex inhibition during muscle fatigue of a close synergist.
Supported b~ N I H G r a n t s NS21180, P01NS 17489, Veterans Administration Merit Review ( W . Z . R . ) , N I H T32NS07243 ( L , H . ) and O N R Fellowship (D.B.).
erties of late adaptation in spinal motoneuroncs of the cat, Exp. Brain Res., 46 (1982) 191-196. 10 Kernell, D. and Monster, A.W., Motoneurone properties and motor fatigue. Exp. Brain Res.. 46 (1982) 197-204. 11 Kniftki, K.D.. Mense, S. and Schmidt, R,F.. Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation, Exp. Brain Res., 31 (1978) 511-522. 12 Marsden. S.D., Meadows, J.C. and Merton, P.A., Isolated single motor units in human muscle and their rate of discharge during maximal voluntary effort. J. Physiol. (Lond. J. 217 (1971) 12-13P. 13 Mense, S. and Stahnke, M., Responses in muscle afferent fibers of slow conduction velocity to contractions and ischemia in the cat. J. Physiol. tLond, 1,342 (1983) 383-397. 14 Nelson, D.A. and Hatton, R,S., Dynamic and static changes in muscle spindle responses during muscle fatigue, Med. Sci, Exerc. Sports. 17 (1985)287-294. 15 Piercy, M.F. and Goldfarb, J,, Discharge patterns of Rensllaw cell evoked by volleys in ipsilateral cutaneous and high threshold muscle afferents and their relationship to reflexes recorded in ventral roots. J. Neurophysiol.. 37 (1974) 294-302. 16 Sherrington, C.S., On plastic tonus and proprioceptive reflexes, Q. J. Exp. Physiol.. 2 (1909) 109-156. 17 Stephens, J.A., Reinking, R.M. and Stuart. D.G., Tendon organs of cat medial gastrocnemius: responses to active and passive forces as a function of muscle length, J. Neurophysiol.. 38 (1975) 1217-1231.
199
Elsevier BRE 22714
Increased inhibitory effects on close synergists during muscle fatigue in the decerebrate cat L. Hayward !, D. Breitbach 2 and W.Z. Rymer 1"3 t Department o f Physiology and :Graduate Program in Neuroscience. Northwestern University and ~Vetermts Administraiion Lakeside Medical Center. Chicago. IL 60611 (U.S.A. J
(Accepted 13 Octobcr 1987) Key words: Muscle fatigue: Reflex inhibition; Synergist: Muscle afferent
We compared the magnitude of reflex inhibition induced in the sol:us muscle by contraction or stretch of the medial gaslrocncmius (MG). before, during, and after electrically induced fatigue of the MG. Our findings are that MG fatigue is accompanied by "lsubstantial increase in solcus inhibition, which then recovers with MG rest. This increased inhibition may explain, at least in part. the dcclinc in motoneuron discharge rate that has been described in fatiguing human muscle.
Investigations of human subjects during maximum voluntary contractions of several different muscles have demonstrated that m o t o r unit discharge rate declines as muscle fatigues -'t2. This rate reduction parallels a slowing in muscle contractile speed, which results, in turn, in a reduction in fusion frequency of motor units It appears that this motor unit rate reduction serves to optimize force generation in fatiguing muscle, by matching neural input to changing muscle contractile p r o p e r t i e ¢ . At the present time the mechanism underlying this neural rate modulation is not fully understood. Some of the decline in m o t o r unit discharge rate may reflect rate adaptation of the m o t o n e u r o n 9"~°. Alternatively, recent investigations by Bigland-Ritchie et al. 3 have suggested a role for a peripheral feedback mechanism. These investigators demonstrated that the motor unit discharge rate, which normally recovers within 3 rain following fatiguing contractions of human muscles, does not recover if the muscle is kept ischemic, despite ample time for motoneuron recovery from the rate-adapted state. These authors propc, sed that these effects are most likely mediated by the reflex actions of the groups III and IV muscle afferents, afferents connected to receptors
that are known to be sensitive to the types of thermal and metabolic stimuli that arise during muscle fatigue ~H3. The present study was undertaken to assess the characteristics of this hypothetical fatigue-related peripheral feedback mechanism. In an animal model, we have examined the effects of fatigue of medial gastrocnemius on the reflex excitability of a non-fatigued synergist (sol:us) known to share many common afferent inputs with medial gastrocnemius ~. Preliminary results have been presented in abstract form s . In 14 decerebrate cats, medial gastrocnemius (MG) and soleus (SOL) were dissected free from the adjacent muscles and severed from their calcaneai attachments. The sural, common peroneal, and tibiai nerves were cut and a hip denervation was also performed. In the main experiments, the nerve to MG was isolated but left intact to allow selective electrical stimulation of the M G muscle. In 5 additional experiments, the M G m u s c l e - n e r v e was sectioned and stimulated proximally (see below). The tendon of SOL was attached to a non-compliant load ceil, and the MG tendon was attached to a similar but separate load cell m o u n t e d in-series with an electromagnetic
Correspondence: W.Z. Rymer, Department of Physiology. Ward 5-295, Northwestern University Medical School. 3113East Chicago
Avenue, Ch!cago, IL 60611. U.S.A. 0006-8993/88/$(13.5(tO 1988 Elsevier Science Publishers B.V. (Biomedical Division)
200 puller. The initial muscle lengths of both SOL and MG were set between 5 and 15 mm less than maximum physiological length. The electromyograms (EMG) of MG and SOL were recorded differentially with pairs of 75-1tm Teflon-coated stainless-steel wires inserted into the muscle bellies. The signals were amplified 100x, band pass filtered over 10-100 Hz, and full-wave rectified, All data (force, EMG and length) were sampled on-line by a PDP 11/73 computer at 5-ms intervals and stored on hard discs for later analysis. Force and EMG activity from MG and SOL were monitored before, during and after selective fatigue of MG. For each trial, an initial isometric SOL force between 5 and 9 N was established by applying mechanical pressure on the contralateral foot, or by torsion of the contralateral ankle and knee, thereby activating the crossed extension reflex ~6. Initial MG force was less influenced by the crossed extension reflex, never exceeding 3.0 N active force. SOL force was then recorded during varying increases in MG force elicited by either different amplitude ramp and hold stretches of MG or by a 3-s period of electrical stimulation of the MG muscle nerve, The ramp stretches of MG were 0.5 s in duration and of an amplitude ranging between 2 and 8 mm. Electrical stimulation of the MG nerve was applied at 1.3 times group I threshold, at frequencies between 20 and 50 Hz. Five to 10 trials of each stretch amplitude and stimulation frequency were recorded both before and after fatigue of MG. Fatigue of MG was elicited by electrical stimulation of its muscle nerve at 1.3 times group I threshold (1.3 × T) and 25 pulses/s, with duty cycles ranging from 3 to ! up to 7 to 1 (ratio of electrical stimulation to rest duration). MG was regarded as being fatigued if force output during tetanic stimulation had dropped to 30% or less of the original value. Following the completion of the fatigue protocol, we immediately resumed sampling force output of SOL and MG in response to the electrical stimulation and ramp strctch protocols outlined above. Post-fatigue measurements were obtained 30-50 rain following the cessation of the fatiguing stimulus. Fig. 1 shows the force responses of SOL and MG to electrical stimulation of the MG nerve (Fig. 1A) and ramp stretch of MG (Fig. 1B), respectively. Before fatigue (thin line), the MG force increase (upper
traces) evoked by either electrical stimulation or stretch is accompanied by a reflexly mediated decrease in SOL force (lower traces). Immediately after fatigue of I~G, force increases comparable to those produced before fatigue evoked much larger reductions in SOL force (see Fig. l, thick lines). Following recovery from MG fatigue, reflex inhibition of the SOL returned to values similar to those evoked before fatigue. To quantify the relations between reflex inhibition of SOL and MG force increase, we calculated the difference between the initial and stimulation-related output for each muscle using two specified time 'windows', placed immediately before and during isometric or stretch stimulation of MG (see filled time windows in Fig. l). This change in muscle force was used for analysis, instead of absolute force, to minimize the influence of crossed extensor related variability of initial muscle force. The initial force range for MG was 0.2-2.9 N and 5-9 N for SOL. The change in SOL force was plotted as a function of the corresponding increment in MG force Fig. 2 (part A, open boxes) shows the responses recorded from a typical non-fatigued preparation, in which the decrement in SOL force increased with increasing stretch-evoked MG force (illustrated by positive slope values). Fig. 2A (filled boxes) shows that the effect of fatigue was to increase the slope of the relation between MG force increment and SOL force reduction, and presumably the sensitivity of the heteronymous inhibitory pathways. A similar increase in the slopes of the regression lines during fatigue occurred in all seven experiments of this type. During stretch stimulation of MG (three experiments), MG fatigue was accompanied by an increase in mean slope of the M G - S O L regression from 0.07 to 0.21 (Newton decrement SOL/Newton increment MG). Slopes were estimated by least squares, forcing the linear regression through the origin. For these 3 preparations the percent increase in slope during fatigue was 176,532 and 645%. During electrical stimulation of MG (4 experiments) there was again an increase in mean slope from 0.35 to 0.78 during fatigue (Newtons decrement SOL/Newton increment MG). The percent increase in slope during fatigue within preparations was 137, 223, 295 and 441%. Because the scatter of data points was often fairly
201
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B. 30,, v
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1
2
3
4
5
6
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2 TIME (S)
3
4
Fig. 1. Effect of MG fatigue on reflex responses in a non-fatigued synergist. SOL. A: the reflex inhibition the SOL (lower trace) elicited during isometric contraction of MG (upper trace), before (thin line) and during (thick line) selective fatigue of MG. Co:~traction of MG was evoked by electrical stimdlation of the MG muscle-nerve at 1.3 times a-threshold for 3 s ~stimulation frequency before fatigue was 40 Hz and 2(} Hz during fatigue). B: the reflex inhibition of SOL (lower trace) during a 6-mm ramp stretch of MG (upper trace), before (thin line) and during (thick line) fatigue of MG. The filled boxes indicate the time "windows" within which average force values for each strial were calculated.
large, summary comparisons of changes in reflex inhibition during fatigue were made primarily using m e a n SOL force reductions, calculated over a narrow band of MG forces. MG force ranges (for example see Fig. 2A) were chosen to include force increases common to all three conditions (before, during and after fatigue). Fig. 2B,C shows the mean decrements in SOL force before, during and after MG fatigue from the 7 experiments. During both isometric (Fig. 2B) and stretch stimulation (Fig. 2C) of MG, inhibition of SOL force increased by at least two-fold during fatigue as compared to before or after fatigue. In all 7 experiments evaluated using this procedure, tile mean decrement in SOL force was statistically greater during fatigue as compared to before and/or after fatigue (t-test, P < 0.01). These fatigue-induced changes in inhibition of the soleus could be mediated by either afferent haput from the fatiguing muscle, or from Renshaw neuron excitation by antidromic activation of motor axons during the fatiguing protocol. To evaluate the former possibility, in 5 experiments we sectioned the MG muscle nerve and electrically stimulated the proximal
end at various stimulus intensities for 3 s (similar to the test paradigm used to elicit reflex inhibition in SOL when the MG muscle-nerve was intact). At low stimulus intensities (within group I range, 1.1-1.5 x 7") and frequencies of 25-50 Hz, little or no effect on SOL force was recorded. At the same stimulus intensities but higher frequencies, 100-200 Hz, small decrements in SOL force production were recorded. However. more substantial reductions in SOL force, such as those seen during muscle fatigue, were recorded only at stimulus intensities at or above 10 x T, stimulus intensities appropriate for activating group !11 and IV afferent fibers 6. To assess the possible inhibitory contribution of antidromic activation of the motor axon during the fatiguing protocol, in one preparation the proximal end of the cut MG muscle-nerve was stimulated for 30 rain at intensities and rates equal to those used to fatigue the muscle (1.3 × T, 3 s, 25 Hz). This repetitive antidromic activation had no effect on ,he electrically mediated threshold of inhibition of SOL force (described above). Thus, the effects seen during fatigue were probably mediated by fatigue-related af-
202 B.
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15
20
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3
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2
30
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0 BEFORE
DURING
AFTER
MG FATIGUE
Fig. 2. Comparisons of the decrement in SOL force elicited by MG force increase, before, during and after fatigue of MG. A: the decrement in SOL force, from a single preparation, plotted as a function of the MG force increase during ramp stretches (4-8 mm) before (I-q), during (B) and after (+) fatigue of MG. The slopes of the regression lines before, during and after fatigue were 0.(13, 0.18 and 0.10 (N SOL/N MG) respectively. Mean changes were determined by calculating the average force decrement in SOL evoked during MG stimulation, within a specified range of MG forces (see Force Window). The graphs in B and C illustrate tht mean decrements in SOL force for 7 preparations during isometric (B) and ramp (C) stimulation of MG. In these 7 experiments the mean decrement in SOL force was significantlygreater during fatigue of MG as compared to before or after fatigue (t-test, P < II.01).
ferent input from the muscle, not from antidromic activation of the motoneuron pool or prolonged excitation of Renshaw cells. Bigland-Ritchie et al. 3 have suggested that the decline of motor unit discharge rate during muscle fatigue may be reflexly mediated by excitation of the small diameter group III and IV afferents. Our reo suits are entirely consistent with this mechanism. Many group III and IV afferents are known to be very responsive to the type of mechanical, metabotic and thermal changes that may occur in muscle during fatigue ll'13. Thus, increases in group Ill and IV discharge during muscle fatigue may be responsible for increased inhibition of homonymous or heteronymous motoneurons, mediated presumably through inhibitory interneurons located in deeper lamina VII of the spinal cord 5. In contrast, it is unlikely that the large diameter
muscle spindle and Golgi tendon organ afferents are primarily responsible for mediating the fatigue-related reflex inhibition. Nelson and Hutton 14 have demonstrated that muscle spindle afferents do not change their response characteristics when the muscle is fatigued by electrical stimulus intensities within the group I range (although the possibility of F-mediated fatigue of intrafusal fibers has not been thoroughly examined). Golgi tendon organ receptor discharge, which is excited by increases in muscle force, would, if anything, be expected to show a relative decline during muscle fatigue tT, giving rise to a decrease in reflex Ib inhibition. One possible additional pathway through which group III and IV afferents may mediate feedback inhibition of motoneurons during fatigue is through increased excitation to the Renshaw cells. These recurrent inhibitory neurons are excited polysynaptically
203 by high threshold muscle afferents tS. Renshaw cell discharge is also contingent upon the discharge of the m o t o n e u r o n s , and Renshaw n e u r o n s , in turn, inhibit m o t o n e u r o n s , making t h e m possible modulators of m o t o n e u r o n discharge rate. T h e r e f o r e , it is possible that during muscle fatigue, increased group 111 and IV input m a y gradually facilitate the R e n s h a w - m e diated recurrent inhibitory p a t h w a y , resulting in progressive reduction of m o t o r unit discharge rate. Furt h e r m o r e , this reflex regulation would be appropriately d e p e n d e n t upon the changing metabolic and thermal state of the muscle, adjusting m o t o n e u r o n output to m a t c h the changing p r o p e r t i e s of the active muscle. Alternative!y, it ~s also k n o w n that the Ib in-
1 Baldissera, F., Hultborn, H. and Illert, M., Integration in spinal neuronal systems. In V.B. Brooks (Ed.), Handbook o.f Physiology. SectionJ. The Nervous S,vslem. Vol. 11, Motor Controt, Part 1, American Physiological Society, Bethesda, MD, 1981, pp. 505-595. 2 Bigland-Ritchie, B.R., Johansson, R.S., Lippoid, O.C.J. and Woods, J.J., Contractile speed and EMG changes during fatigue of sustained maximum voluntary contractions, J. Neurophysiol., 50 (1983) 313-324. 3 Bigland-Ritehie, B.R., Dawson, N.J., Johansson, R.S. and Lippold, O.C.J., Reflex origin for the slowing of motoneurone firing rates in fatigue of human voluntary contractions, J. Physiol. ( Lond. l, 378 (1986) 451-459. 4 Bigland-Ritchie, B.R. and Woods, J.J., Changes in musclc contractile properties and neural control during human muscular fatigue. Muscle Nerve, 7 (1984) 691-699. 5 Cleland, C., Rymer, W.Z. and Edwards. F., Force sensitive interneurons in the spinal cord of the cat. Science, 217 (1982) 652-655. 6 Eccles, R.M. and Lundberg, A., Synaptic actions in motoneurones by afferents which may evoke the flexion reflex, Arch. ital. Biol.. 97 (1959) 199-221. 7 Harrison, P.J. and Jankowska, E., Sources of input to interneurons mediating group I non-reciprocal inhibition of motoneurons in the cat, J. Physiol. (Lond.L 361 (1985) 379-401. 8 Hayward, L., Breitbach, D. and Rymer, W.Z., Increased inhibitory effects on close synerg~.stsduring muscle fatigue, Soc. Neurosci. Abstr., 13 (1987) 1532. 9 Kernell, D. and Monster, A.W., Time course and prop-
terneurons 7 and force sensitive interneurons 5 receive excitatory input f r o m the same groups of high threshold muscle afferents, raising the possibility that the gain of the lb and o t h e r inhibitory pathways m a y also be modulated during muscle fatigue. T h e results from o u r e x p e r i m e n t s simply confirm that there is an increase in h e t e r o n y m o u s reflex inhibition during muscle fatigue of a close synergist.
Supported b~ N I H G r a n t s NS21180, P01NS 17489, Veterans Administration Merit Review ( W . Z . R . ) , N I H T32NS07243 ( L , H . ) and O N R Fellowship (D.B.).
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