Department of Physiology, Emory University, Atlanta, Georgia 30322
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ABSTRACT |
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Nichols, T. Richard Receptor mechanisms underlying heterogenic reflexes among the triceps surae muscles of the cat. The soleus (S), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles of the cat are interlinked by rapid spinal reflex pathways. In the decerebrate state, these heterogenic reflexes are either excitatory and length dependent or inhibitory and force dependent. Mechanographic analysis was used to obtain additional evidence that the muscle spindle primary ending and the Golgi tendon organ provide the major contributions to these reflexes, respectively. The tendons of the triceps surae muscles were separated and connected to independent force transducers and servo-controlled torque motors in unanesthetized, decerebrate cats. The muscles were activated as a group using crossed-extension reflexes. Electrical stimulation of the caudal cutaneous sural nerve was used to provide a particularly strong activation of MG and decouple the forces of the triceps surae muscles. During either form of activation, the muscles were stretched either individually or in various combinations to determine the strength and characteristics of autogenic and heterogenic feedback. The corresponding force responses, including both active and passive components, were measured during the changing background tension. During activation of the entire group, the excitatory, heterogenic feedback linking the three muscles was found to be strongest onto LG and weakest onto MG, in agreement with previous results concerning the strengths of heteronymous Ia excitatory postsynaptic potentials among the triceps surae muscles. The inhibition, which is known to affect only the soleus muscle, was dependent on active contractile force and was detected essentially as rapidly as length dependent excitation. The inhibition outlasted the excitation and was blocked by intravenous strychnine. These results indicate that the excitatory and inhibitory effects are dominated by feedback from primary spindle receptors and Golgi tendon organs. The interactions between these two feedback pathways potentially can influence both the mechanical coupling between ankle and knee.
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INTRODUCTION |
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Evidence has accumulated that heterogenic, or
intermuscular, spinal reflexes play an important role in determining
the mechanical properties of multisegmented limbs and in coordinating
the component joints (Gielen et al. 1988; He et
al. 1991
; Hogan 1985
; Nichols 1994
). These reflexes depend on the fundamental variables,
length and force. Furthermore they link muscles with similar lines of action at a given joint in the case of length feedback, and they couple
antigravity muscles that cross different joints in the case of force
feedback (Nichols 1989a
, 1994
). Because of the
dependencies on length and force, it is natural to assume that the
underlying pathways arise from muscle spindles in the case of
length-dependent reflexes and from Golgi tendon organs in the case of
force-dependent reflexes. In view of the uncertain roles of these two
receptors in limb coordination, however, it is important to determine
the basis of heterogenic reflexes in specific receptors and pathways.
The primary receptors of muscle spindles have been shown to constitute
the dominant receptor component of the autogenic stretch reflex
(Houk and Rymer 1981; Houk et al. 1981
)
and the myotatic unit (Bonasera and Nichols 1996
;
Lloyd 1946
; Nichols 1989b
;
Nichols and Koffler-Smulevitz 1991
) based on dynamic
characteristics, distribution to antagonists, and latency. Group Ia
afferents also provide excitatory feedback to all the triceps surae
motoneuron pools (Burke et al. 1976
; Eccles et
al. 1957a
, 1962
; Scott and Mendell 1976
).
Prochazka (1990)
has estimated the relative
contributions of primary and secondary spindle afferents from all three
muscles of the triceps surae to depolarization of motor units of the
medial gastrocnemius muscle during locomotion, but insufficient data are available to determine the contributions to lateral gastrocnemius and soleus muscles as well. Therefore the contributions of spindle receptors to heterogenic reflexes in the triceps surae during active
contractions remain unknown.
Group Ib afferents from Golgi tendon organs are thought to have a wider
distribution among limb muscles than group Ia afferents (Eccles
et al. 1957b; Jami 1992
; Jankowska
1992
; Powers and Binder 1985
). The potentially
short latencies associated with these receptors make them good
candidates for the force-related inhibition that links a variety of
load-bearing muscles in the cat hindlimb (Nichols 1994
).
Step-wise regression analyses have revealed for some muscle combinations that the inhibition strongly depends on the force of the
muscle of origin (Bonasera and Nichols 1994
). However, the adequate stimulus for the Golgi tendon organ is active
contractile force rather than total force (Houk and Henneman
1967
). Therefore a relationship between reflex effect and
active force would establish more firmly the role of the Golgi tendon
organ in the reflex inhibition.
The purpose of the experiments reported here was to obtain further insights into the receptor mechanisms underlying heterogenic reflexes among the triceps surae in the decerebrate cat. It was found that excitatory feedback under conditions of muscle activation was distributed approximately according to heteronymous Ia linkages determined under quiescent conditions. Inhibitory feedback from the gastrocnemius muscles to soleus was found to depend on active contractile force and to act essentially as rapidly as the stretch reflex, supporting the hypothesis that this feedback arises from Golgi tendon organs. New information concerning the duration of the inhibition also was obtained. Finally, the inhibition could be blocked using strychnine, indicating a glycinergic and postsynaptic basis.
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METHODS |
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The data presented here were drawn from experiments on 32 adult
cats of either sex. The methods have been described in detail elsewhere
(Bonasera and Nichols 1994; Nichols
1987
), so only a brief description with aspects relevant to
this study is provided. All protocols are in complete accordance with
the guidelines of both the National Institutes of Health and the Emory
Institutional Animal Care and Use Committee.
Surgical preparation
Under halothane or isoflurane anesthesia, the animal underwent tracheotomy, bilateral carotid ligature, and cephalic vein cannulation. Core temperature was maintained at ~37°C using a rectal temperature controller and a heat lamp. Fluids were infused through the venous cannula. Two steel pins welded to small metal blocks were inserted longitudinally into the tibia and femur at the right knee to provide fixation. After intercollicular decerebration, the right caudal cutaneous sural nerve was dissected free and the right triceps surae muscle group dissected from surrounding connective tissue. Thread markers were placed around the fibula and through the tendons of each of the triceps muscles for setting muscle length with respect to a standard length (L90) corresponding to a 90° ankle angle. The knee was set to an angle of ~110°. In some experiments, the lateral (LG) and medial gastrocnemius (MG) muscles were separated and in others they were left intact. The tendons of the gastrocnemius and soleus (S) were separated from their attachments on the calcaneus with a small bone chip on each tendon. The tendons were fitted with small clamps for attachment to the torque motors. The posterior tibial nerve was freed near the ankle in both limbs for stimulation. The limb was immobilized using hip pins attached to the stereotaxic frame, and the bone pins and an ankle clamp fixed to mechanical ground by magnetic bases. At the end of the experiment, the animal was euthanized with an overdose of pentobarbital and a pneumothorax was performed.
Mechanical stimulation and recording
Muscle length was controlled using two rotary servomotors and precision potentiometers. Linear positioning was achieved by connecting the motor pulleys to linear ball slides by stainless steel cables. Elastic bands were used to cancel the tendency for the cables to unwind and exert force against the muscle. Therefore motor-shaft position corresponded to ball slide position, and the potentiometer signal could be used to measure muscle length. Force was measured using strain-gauge myographs mounted on the ball slides through miniature universal joints to ensure alignment between myograph and muscle. The myographs were manufactured in the laboratory using semiconductor strain gauges mounted on U-shaped aluminum beams. Stiffness in tension of the combined myograph and servomotor system exceeded 200 N/mm.
A personal computer with custom software was used to actuate the motors in the appropriate sequence (see next section), provide the ramp and hold input signals, and acquire the length, force and electromyographic (EMG) data. Samples were acquired at the rate of 500 Hz and with a precision of ~0.05 N. Analogue sample/hold modules were used to extract changes in force and initial force from the total force signal prior to sampling. The sampled initial force and subsequent change in force signals were stored during each trial.
Experimental design
Initial lengths and forces were controlled for each muscle.
Initial lengths were set electronically through the feedback
controller. In most experiments, except where noted, muscles were held
at standard initial lengths (L90) corresponding to an ankle angle of
90° and a knee angle of 110°. The duration and amplitude of the
ramp and the duration of the hold period were set under software control. Muscle force was modulated by evoking either a
crossed-extension reflex through electrical stimulation of the
contralateral tibial nerve or by stimulating the ipsilateral, caudal
cutaneous sural nerve (Figs.
1-3).
The stimulation rate for all three nerves was 50 pps. For both
reflexes, force increased rapidly then declined slowly. The sural nerve
reflex was included to decouple forces in the medial gastrocnemius
muscle (MG) from the force in the soleus muscle (SOL) (Clark et
al. 1993; Kanda et al. 1977
; Labella et
al. 1989
). Stimulation of this nerve resulted in two different patterns of response in SOL. This muscle was either inhibited initially
followed by a delayed excitation (Fig. 1) or it was activated weakly
with the same time course as the strong activation of MG (Fig. 3). In
the latter case, therefore, the force in SOL was maintained over a
narrower range compared with the force in the gastrocnemius muscles.
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In a given experimental trial, either or both muscles were stretched by
4 mm at a constant velocity of either 40 or 20 mm/s. The amplitude was
chosen to approximate the magnitude of the stretch of SOL during the
E2, or yield, phase of the step during trotting (Goslow et al.
1973). The hold period was set at 350 ms. Each experimental
trial consisted of a stretch of one or both muscles. Trials were
conducted as muscle force slowly decayed to obtain responses at
different levels of initial force. In cases in which all three muscles
of the triceps surae were involved, one muscle was connected to an
isometric myograph so that its force could be measured during stretch
of either or both of the other muscles (see Fig. 1).
The stretches were sequenced according to one of two protocols. In
protocol 1, a single muscle was stretched in each trial (Fig. 1). Forces in the stretched muscle as well as isometric forces in
one or two others were measured. Responses of the stretched muscle
consisted of intrinsic and stretch reflex components (Nichols and Houk 1976), and responses of the isometrically constrained muscles consisted of heterogenic reflex components only. Mechanical artifacts due to direct mechanical action of the stretched muscle on
those isometrically constrained were indicated by essentially instantaneous latencies or by effects observed after pharmacological block of heterogenic reflexes. The motors were repositioned so as to
minimize these artifacts. Trials were rejected if these artifacts
exceeded 5% of the total response. In protocol 2, one muscle (1) was stretched on each trial and the other
(2) on alternate trials (Fig. 3). Using this protocol, the
interaction of intermuscular reflexes from muscle 2 and the
stretch reflex from muscle 1 was measured. Because the
triceps surae muscles were all stretched during the yield phase of
movement (Goslow et al. 1973
), protocol 2 better approximates natural conditions. Protocol 1 was
employed mainly to observe reflex effects in isolation from the complex intrinsic properties of stretched muscle (Hayward et al.
1988
).
In six experiments, 0.7 mg strychnine was injected intravenously in
graded doses to block inhibitory reflexes. In two of these experiments,
the animals were pretreated with the
N-methyl-D-aspartate (NMDA) antagonist
D(
)-2-amino-7-phosphonoheptanoic acid (DAP7) through the intrathecal
route. In one additional experiment, the broad spectrum excitatory
amino acid antagonist kynurenic was injected intrathecally. A small
laminectomy was performed at a low thoracic level, and an intrathecal
cannula inserted caudally under the dura to the L7 level. In the case
of DAP7, 1-3 mg dissolved in
500 µl of saline, and in the case of
kynurenic acid, 1.25 mg in 300 µl of saline, was injected. Control
measurements were obtained before and after insertion of the cannula
and after infusion of drug. These drugs did not alter either the
relationship between the magnitude of the stretch reflex and initial
force or the corresponding magnitudes of inhibition, but they did
substantially reduce the tendency of the preparations to exhibit
seizures (Nichols and Koffler-Smulevitz 1991
). This
procedure therefore made it possible to achieve near complete block of
the inhibition with reduced risk of seizures. In a previous experiment,
kynurenic acid in a similar dosage did reduce the gain of the stretch
reflex by about 10% (Nichols and Koffler-Smulevitz
1991
). Because it is known that kynurenic acid blocks non-NMDA
as well as NMDA receptors (Stone and Burton 1988
), the
small reduction in reflex gain in one case indicates that the dosage
used here may have been near the threshold for non-NMDA receptors that
mediate synaptic transmission from group Ia afferents to motoneurons
(see Jahr and Yoshioka 1986
). Because the effects of
kynurenic acid on reflex gain were small and variable, we attribute the
effects of this drug in reducing seizure activity to its effects on
NMDA receptors.
Data analysis
Force responses were collected into groups according to muscle
species and protocol. Responses formed a single group for
protocol 1 (Fig. 2) and two groups for protocol
2. In the latter case, one group consisted of muscle responses
obtained with the stretch of muscle 1 only. The other group
consisted of responses taken with stretch of muscles 1 and
2. Latencies of any changes in force were checked to rule
out mechanical artifacts. The latency for a mechanical effect in the
stretched muscle was essentially instantaneous due to the intrinsic
mechanical responses of the active motor units (Fig. 2, MG). Excitatory
or inhibitory reflex effects occurred with a latency of ~16 ms (Fig.
2, LG and SOL), which interval is less than or equal to the
response time of the earliest components of the stretch reflex in other
systems (Bonasera and Nichols 1994; Nichols and
Houk 1976
). Baselines for each response were estimated using a
linear regression of samples obtained during the first and last 50 ms
of each record. Measurements of the magnitudes of each response at
selected time points then were made from the fitted baselines.
Responses were measured at the end of the ramp stretch ("dynamic"
response) and at the end of the hold phase ("static" response).
Although the force responses included both active and passive
components, the initial lengths of the muscles were chosen in part to
minimize the passive components. These measurements then were plotted
versus the initial forces of either muscle (Figs.
4, 5, 8, and 9). The initial
forces were obtained from voltages stored in the sample/hold modules
during the experiment. The points for a given group of responses were
fitted by a quadratic polynomial and plotted along with the 95%
confidence limits. Comparison of the two lines obtained under
protocol 2 revealed the sign of the net reflex effect and
the dependence of this effect on background force.
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RESULTS |
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Excitatory reflexes
In four preparations in which MG, LG, and SOL were independently stretched according to protocol 2, it was found that these three muscles were linked by excitatory reflexes (Figs. 4 and 5). These excitatory actions were generally found to be independent of initial force for a substantial range of forces (Figs. 4 and 5). That is, the absolute increase in force due to the heterogenic reflex was approximately constant over the range of initial forces. The heterogenic effect also could be expressed as a percentage increase over the autogenic force response (Figs. 4 and 5). The strongest effects were found consistently to extend from either MG or SOL onto LG (Fig. 4, A and C), and the weakest heterogenic reflexes extended from either SOL or LG onto MG (Fig. 4, B and D). In 15 other preparations in which MG and LG were left intact and stretched as a group to minimize muscle damage, excitation with similar characteristics occurred between SOL and the gastrocnemius muscles (G). In preparations with weak inhibitory reflexes, substantial excitation from the gastrocnemius muscles onto SOL also was observed for a wide range of forces (Fig. 5). Using measurements obtained according to protocol 1, latencies of ~15-20 ms were found for this excitation (Fig. 2).
Inhibitory reflexes
As previously described for a more limited set of data
(Nichols 1989a), inhibitory reflexes were observed for
reflexes from either LG or MG onto SOL but not in the reverse
direction. This inhibition increased with force and cancelled the
short-latency excitation at the highest forces (Fig. 2, SOL).
Therefore, the latencies of inhibition and excitation appeared to be
comparable. These interactions are illustrated further in Figs.
6 and 7 for a case in which LG and MG were left intact and activation was achieved
using a crossed-extension reflex. Pairs of records of the stretched G
and isometric SOL are shown for a range of initial forces (Fig. 6). The
relatively brief excitation at low forces and prolonged inhibition at
high forces are apparent from the figure. The brief excitation onto SOL
contrasts with the excitation from MG onto LG that mirrors the duration
of the stretch (Fig. 2, LG). The transition from net inhibition to
excitation as force declined is further illustrated in Fig. 7. For each
10 ms during the experimental record, quadratic polynomials were
constructed from the responses of SOL and the corresponding initial
forces (see METHODS). These polynomials were concatenated
and are shown in Fig. 7 as a surface that relates response magnitude to
initial force and time. The gradual emergence of excitation and
decrease of inhibition as force declines can be explained provisionally by summation of the two reflexes and force dependence of the inhibitory component. It can be argued that the excitation itself does not decline
as force increases, because it remains high over a wide range of forces
in preparations in which the inhibition is weak (Fig. 5). The
excitatory component has a rapid onset and a dynamic phase, whereas the
inhibitory component develops more slowly and outlasts the excitatory
component.
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The inhibition from G onto SOL was found to depend mainly on the force
in the muscle of origin. This conclusion was reached by comparing the
extent of inhibition during activation by crossed-extension and sural
nerve reflexes. In the former case, forces in both muscles covaried
over a large range (Fig. 1). In the latter case, force in G was
modulated widely, whereas the force in SOL varied over a more limited,
low range (Fig. 3). Static responses obtained under protocol
2 are shown plotted versus the initial force in G for both forms
of activation in Fig. 8A. The
responses of SOL were smaller in the case of sural nerve stimulation
because the background forces are low for this muscle, but the
transitions from net inhibition to net excitation occurred at similar
initial forces of G. In the case shown in Fig. 8, the transitions from net inhibition to excitation for the static responses occurred at ~5
N (4.8 and 5.0 N) in G for either reflex. The corresponding forces in
SOL, however, were 2.2 N for the crossed-extension reflex and only 1.2 N for the sural nerve reflex. In the case of the dynamic responses, the
transitions occurred at ~9 N in G for either reflex. The
corresponding forces in SOL, however, were ~8 N for the
crossed-extension reflex and only 2 N for the sural nerve reflex. These
results are summarized in Fig. 8B in relation to the initial
forces in SOL and G for both reflexes. The transition forces that
corresponded to the dynamic and static responses are indicated by
arrows. The fact that these transitions were less dependent on the
force in SOL than on the force in G indicates that the balance between
excitation and inhibition was determined primarily by the feedback from
G and not by the conditions of activation in SOL. In another
experiment, the transition forces for the two reflexes varied by
~10% for the forces of G (13 vs. 12.5 N) and threefold for the
forces of SOL (3 vs. 1 N). In addition, the magnitudes of inhibition at
corresponding levels of initial force were similar for the two forms of
activation and therefore were related primarily to the force in the
muscle of origin of the inhibitory reflex. The interpretation of this
experiment is complicated somewhat by the fact that MG and LG initially
are activated in different proportions during the two reflexes (Fig. 1)
(Nichols et al. 1993), so the sources of the inhibition
might have differed early during each trial. However, SOL receives
strong inhibition from both MG and LG, and the transition forces in the gastrocnemius muscles as a group were quite similar for both reflexes.
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Evidence was obtained that the inhibition was related to active contractile force rather than total force during three experiments in which the initial length of G was varied systematically. Records were obtained according to protocol 1 during crossed-extension reflexes (Fig. 9). At each initial length of G, the initial forces of the two muscles varied according to straight-line relationships (Fig. 9B), but these relationships differed according to slope and intercept. The differences in intercept reflect the different passive forces of G at each length. The different slopes presumably reflect the increased force-generating capacity of G at the longer lengths. Active contractile forces of G were obtained by subtracting the passive (intercept) forces from the measured initial forces. When the responses of SOL were plotted against the calculated active force of G, the points corresponding to different initial lengths of G fell on a single line (Fig. 9A). These results indicate that the magnitude of inhibition from G onto SOL was related to the active, initial force of G but not the total force.
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It was demonstrated further in six preparations that the
inhibition could be blocked using an intravenous injection of
strychnine with or without pretreatment with antagonists of excitatory
amino acids (see METHODS). Results from such an experiment
using protocol 2 are shown in Fig.
10. In this experiment, the inhibition
was particularly strong throughout the range of forces (Fig. 10,
top). Control data were obtained before and after insertion
of an intrathecal cannula to infuse DAP7 (see METHODS) and
after infusion of DAP7 (shown in Fig. 10, top). At an
intravenous dose of 100 µg of strychnine, autogenic responses of SOL
were unaltered, but the inhibition was reduced significantly (Fig. 10,
middle). At a dose of 200 µg, autogenic responses ()
were slightly elevated and the inhibition was essentially absent (Fig.
10, bottom). The elevated autogenic reflex could indicate
that some autogenic inhibition had been present, but the main result
was the complete block of heterogenic inhibition from G onto SOL. This
finding suggests that the inhibition is postsynaptic and glycinergic
(Lodge et al. 1977
; Pratt and Jordan
1987
) and that it sums with the stretch reflex to produce combinations of excitation and inhibition (Fig. 7) (see Nichols and Koffler-Smulevitz 1991
). Similar results were obtained
using strychnine alone or using intrathecal kynurenic acid as a
pretreatment.
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Although inhibition was observed only from MG, LG, or G onto SOL, the extent of this inhibition varied markedly from preparation to preparation. This variability is apparent from a comparison of the force level at which inhibition supercedes excitation in different preparations. The range of the variability is illustrated by comparing Figs. 5 and 10 (top). The inhibition was expressed over the entire range of initial forces in the latter but was absent over most of the range in the former. In most experiments, the magnitude of the inhibition was intermediate between these two extremes.
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DISCUSSION |
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Mechanisms
The data presented in this paper can be explained most simply
using known properties of primary receptors of muscle spindles and
Golgi tendon organs and their homonymous and heteronymous projections
within the triceps surae muscle group. The earliest detectable
excitatory effects, both autogenic and heterogenic, occurred at ~16
ms after the initiation of muscle stretch. This number corresponds to
that obtained for the long toe flexors (Bonasera and Nichols
1994) and is less than the 23 ms obtained for the stretch
reflex of SOL using a different stretching device (Nichols and
Houk 1976
). Considering that the time interval of 16 ms
includes the events between sensory coding of mechanical inputs and
force production in the muscle, a rapid spinal pathway is probably
responsible for this earliest response. Assuming Lloyd's
classification of afferent fibers (Lloyd 1943
) and an
afferent conduction distance of 150 mm for the feline triceps surae
muscles, afferent fibers in the group III range would require 5-25 ms
for the afferent limb of the response alone. Therefore afferents in the
group II or group I range are implicated in these early excitatory
responses. Because the monosynaptic group II inputs from muscle
spindles are relatively weak (Prochazka 1990
), group Ia
afferents from primary muscle spindle receptors are more likely
candidates to mediate these rapid responses, although a role for group
II afferents cannot be excluded.
An additional clue concerning the afferent pathways involved in the
early excitatory responses is the independence of the response on
initial force as observed for other combinations of Ia synergists, such
as peroneus longus and peroneus brevis, and flexor digitorum longus and
flexor hallucis longus (Bonasera and Nichols 1994,
1996
). Similar results were obtained for reciprocal inhibition,
another system that is thought to be mediated by Ia afferents (peroneus
brevis and tibialis posterior: Bonasera and Nichols
1996
; tibialis anterior and soleus: Nichols and
Koffler-Smulevitz 1991
). The fact that the heterogenic
excitation was less dependent on initial force than the stretch reflex
itself (Hoffer and Andreassen 1981
) can be explained
provisionally by the absence of intrinsic muscle stiffness in the
heterogenic response (Hayward et al. 1988
). The stretch
reflex is composed of the stiffness of contracting motor units and
additional force contributions of recruited motor units (Cordo
and Rymer 1982
; Nichols and Houk 1976
). The
progressive increase in the former component with force is thought to
account for the increase in autogenic reflex with force. In the case of an heterogenic reflex, however, the force increase results solely from
recruitment of new motor units and therefore should depend on force to
a lesser extent. Some increase in heterogenic reflex magnitude might be
expected based on the recruitment nonlinearity (Houk et al.
1970
), but this increase is apparently limited even for the
reflex component of the stretch reflex (Hoffer and Andreassen 1981
). Saturation of motor unit recruitment or firing rate
might account for this limitation.
The hypothesis that heterogenic excitation is due mainly to feedback
through Ia afferents is strengthened further by considering the
distribution of excitatory effects among LG, MG, and SOL. Figure
11 shows, in histogram form, the
fractional heteronymous excitatory postsynaptic potential
(EPSP) amplitudes obtained by Eccles et al.
(1957a) using animals anesthetized with pentobarbital sodium. Figure 11 also shows the data obtained in Nichols
(1989a)
of the distribution of excitatory mechanical effects,
expressed as a percentage of autogenic response, obtained in
decerebrate preparations under quiescent conditions. Both sets of data
agree substantially in that MG receives the weakest relative input and LG the strongest. The data can be explained largely by a combination of
Ia projection frequencies (Scott and Mendell 1976
) and
spindle numbers (Chin et al. 1962
). The autogenic
response of LG is increased substantially by stretch of MG and SOL
because MG and SOL contain approximately twice as many muscle spindles
as LG. The relatively small responses of MG can be related to the lower
heteronymous projection frequency from LG and SOL and the smaller
number of muscle spindles in LG.
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These trends are also observed during activation of the triceps surae
(Figs. 4 and 5), supporting the
major contribution of the monosynaptic Ia afferents to heterogenic
excitation under these conditions. No longer latency effects, which
might have been attributed to group II spindle receptors, were noted,
although such effects might not be distinguishable due to the filtering properties of muscle. Given the longer latencies of these pathways and
the smaller size of group II EPSPs (Prochazka 1990), any
such effects might not have been discernible in the present
experiments.
Arguments based on time course, distribution, and force dependence also
can be used to support the hypothesis that the heterogenic inhibition
from MG or LG to S includes feedback from Golgi tendon organs. Despite
the delays associated with oligosynaptic transmission (Eccles et
al. 1957b), the inhibitory action occurred early enough to
progressively diminish what is presumed to be monosynaptic excitation
as initial force increased (Fig. 7). The inhibition also outlasted the
excitation (Figs. 2 and 7). The longer duration of the inhibitory
component is consistent with the longer duration and dispersion of
latencies of inhibitory postsynaptic potentials compared with Ia EPSPs
(Eccles et al. 1957b
; Fetz et al. 1979
; Hamm et al. 1987
; Watt et al. 1976
).
Additional temporal spread in inhibitory action could come about
because of asynchronous recruitment of inhibitory interneurons. This
temporal spread would be expected to apply less to the monosynaptic
pathways for the excitatory component. An additional factor that could
account for the relatively shorter duration of the excitatory response is the brevity of the initial burst in the response of the primary ending of the muscle spindle (Houk et al. 1981
).
The finding that the inhibition is long lasting is in apparent conflict
with recent data concerning inhibitory fading. In cats anesthetized
using either chloralose or pentobarbital, Zytnicki et al.
(1990) showed that electrical stimulation of motor units produces inhibitory effects in motor units that fade within 100 ms even
in the presence of ongoing stimulation and receptor discharge. These
authors suggested that the effect could be due to presynaptic inhibition of Ib afferent fibers onto other Ib afferents. They also
suggested additional hypotheses including a decrease in synchrony of Ib
interneurons or changes in conductance of motoneuronal membranes. Subsequent work suggested that pathways from group II or even group III
afferents might be involved (LaFleur et al. 1993
) and that the transient nature of the inhibition occurs in other inhibitory systems (Heckman et al. 1994
). The reason why the
inhibition did not subside more rapidly in the studies described here
is not clear. However, in the preceding quoted studies that showed
rapid adaptation of the inhibition, the inhibitory responses were
evoked by electrical stimulation of peripheral nerves or synchronous activation of motor units. In the studies reported here as well as
previously (Bonasera and Nichols 1994
, 1996
),
inhibitory effects were evoked by muscle stretch and lasted for the
several hundred milliseconds during which the muscle was held at the
longer length. In a study from another laboratory (Hayward et
al. 1988
), stretch-evoked inhibition was maintained for >2 s.
Therefore the manner in which the inhibitory reflexes were evoked
appears to influence the time course of the reflex effect. The apparent
discrepancy in results could be explained in a number of ways, such as
a difference in the synchrony with which the afferent fibers were
activated or the composition of the population of stimulated afferents.
In any case, the present results as well as the previous results using
muscle stretch suggest that there are important inhibitory reflexes
that are not limited to transient conditions (cf. Heckman et al.
1994
).
When the triceps surae muscles are stretched as a group, the autogenic
response of SOL will be altered by the excitatory and inhibitory
heterogenic components from MG and LG. The extent of the alteration
will depend on the strength of the inhibition, but the dynamic phase of
the response generally will be enhanced due to the addition of
autogenic and heterogenic excitation. In contrast, the static phase
will tend to be diminished due to the longer-lasting inhibitory
component from MG and LG. The assumption that the various sources of
feedback sum in the recipient motoneurons is supported by the finding
that the inhibition can be blocked by strychnine, a potent blocker of
gluycinergic, postsynaptic inhibition (Lodge et al.
1977).
Electrophysiological studies (Eccles et al. 1957b;
Powers and Binder 1985
) have suggested that extensor
muscles at several joints are interconnected by inhibitory feedback
from Ib afferents. Therefore the occurrence of some inhibitory feedback
among the triceps surae was expected, although the inhibition is not
expressed for all combinations of these muscles (Nichols 1989a
,
1994
). Data from the 32 experiments described here confirmed
that no short latency, inhibitory feedback onto either MG or LG is
detectable using these methods. Therefore the net reflex responses of
LG and MG during stretch of the triceps surae group are composed primarily of the autogenic responses and heterogenic excitation from
the other two members of the triceps surae group.
Although several studies have documented the relationships between
heterogenic inhibition and muscle force (Bonasera and Nichols 1994, 1996
; Nichols 1989b
), the results
presented here extend the previous work by further defining the
adequate stimulus of the inhibition. The use of the sural (caudal
cutaneous sural) nerve and crossed-extension reflexes made it possible
to decouple the activation patterns of the triceps surae to determine
whether the inhibition required activation in all three muscles or only the presumed muscles of origin. The sural nerve reflex primarily activates MG (Hagbarth 1952
; Labella et al.
1989
) initially, and then may activate other motor units with
some delay (Fig. 1). This pattern of activation is preparation specific
because SOL is activated simultaneously with MG, in some cases even
though the forces are much smaller (Fig. 3). In contrast to either
pattern of activation through sural nerve stimulation, the
crossed-extension reflex activates all three muscles (Fig. 1). A
complication of this method is that the source of the inhibition
probably did change to some extent from MG during the sural nerve
reflex to a combination of MG and LG during the crossed-extension
reflex. This problem is mitigated, however, by the fact that both MG
and LG are important sources of inhibitory feedback to SOL
(Nichols 1989a
). Another problem could have arisen if
the two reflexes activated different ensembles of motor units within MG
such that different numbers of Golgi tendon organs had been stimulated. It is assumed that the population of activated tendon organs is the
same for a given force during either reflex because size-ordered motor
unit recruitment is preserved in both cases (Clark et al. 1993
; Cope and Pinter 1995
).
Besides the short latency of the inhibition, the other major evidence
for the participation of Golgi tendon organs was the finding that the
inhibition is related to active contractile force rather than total
force. Houk and Henneman (1967) established that tendon
organs have low thresholds to active forces and that the adequate
stimulus is contractile force exerted by the muscle fibers directly in
series with the receptors. It has been shown that the discharge
frequency of tendon organs in the cat soleus muscle is a good predictor
of active muscle force (Crago et al. 1982
;
Stauffer and Stephens 1977
; but see
Horcholle-Bossavit et al. 1990
). In view of this
evidence, it is parsimonious to conclude that the inhibition results
from pathways arising from Golgi tendon organs in MG and LG. However,
it cannot be excluded on the basis of this data that the inhibition
could result from recurrent inhibition (Hamm 1990
). This
possibility is unlikely in view of the evidence that heterogenic
inhibition is markedly reduced in the soleus muscles of animals in
which LG and S had been self-reinnervated and consequently have reduced
proprioceptive feedback emanating from those muscles (Cope et
al. 1994
).
Functional considerations
The asymmetrical distribution of excitation among the triceps
surae has biomechanical consequences. In association with the smaller
numbers of spindle receptors in LG compared with MG and SOL
(Chin et al. 1962), the autogenic reflexes in LG are
smaller than those on MG (Figs. 4 and 5). The larger fractional EPSPs from MG onto LG (Eccles et al. 1957a
) apparently lead to
the larger heterogenic excitation in that direction (Fig. 4 and 5). The
net result is that when the triceps surae are lengthened, the net reflex responses in MG and LG tend toward the same magnitude. Therefore
the line of action of the response of the muscle group will be some
average of the force vectors of the two muscles (Lawrence et al.
1993
; Nichols et al. 1993
). When MG is activated
individually with the suppression of LG and S, as occurs during a sural
nerve reflex, the direction of pull should be dominated by that of MG because this muscle receives most of its excitatory feedback
autogenically and because reflex responses of LG should be suppressed.
This evidence supports the hypothesis that the mechanical actions of MG
on the ankle are unique among the triceps surae because this muscle
provides a significantly larger component of abduction torque than
either SOL or LG.
It has been argued elsewhere that the inhibitory reflexes from MG and
LG to SOL are associated with the differences in action of these
muscles at the knee rather than their different motor unit compositions
(Dacko et al. 1996; Nichols 1989a
). The
data presented here provide further details concerning the dynamics of
the resulting reflex activity in the triceps surae muscles. Early
during the response to stretch of the triceps surae, mixed inhibition
and excitation from MG and LG onto SOL preserves or enhances the
dynamic phase of the stretch reflex of SOL so that the response of the
triceps surae as a whole is dominated by shared excitation. After the
excitatory effect from LG and MG has declined, the remaining inhibition
reduces the magnitude of the tonic stretch reflex in SOL. This later
phase of the response therefore is dominated by the stiffness of MG and
LG. Because these muscles span both ankle and knee joints, the extent
of coupling of the two joints is increased with a consequent increase
in stability.
This interpretation of the role of inhibition in interjoint coupling
and limb stability is subject to the expression of positive force
feedback during some motor behaviors (Pearson 1995).
Excitatory, group I feedback can help regulate the pattern of
locomotion as well as provide a loading reflex to enhance the activity
of antigravity muscles (Dietz et al. 1989
). If
inhibitory force feedback was replaced entirely by excitatory feedback
during a given behavior, then the preceding arguments concerning the
stabilizing effects of force feedback would not apply during that
behavior. However, little information is available concerning the
expression and distribution of these two types of force feedback during
natural behaviors. Recent evidence using intramuscular stimulation in the standing cat, for example, suggested that both types of feedback can coexist with different distributions (Pratt 1995
).
Although instances of positive force feedback were shown during
standing, stimulation of LG still led to inhibition of SOL
(Pratt 1995
). The force feedback system appears to be
subject to considerable flexibility, as indicated by studies of
locomotion and standing as well as the variability of inhibition
observed among preparations reported here.
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ACKNOWLEDGMENTS |
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The author thanks Dr. Timothy C. Cope for valuable comments on the manuscript, two anonymous reviewers for valuable feedback, and M. Witten and D. Koffler-Smulevitz for programming assistance.
This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-20855.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 2 February 1998; accepted in final form 19 October 1998.
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REFERENCES |
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