1Department of Physiology, Medical School, Emory University, Atlanta, Georgia 30322; and 2Department of Physiology, Northwestern University Medical School, Chicago, Illinois 60611
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ABSTRACT |
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Haftel, Valerie K., Jonathan F. Prather, C. J. Heckman, and Timothy C. Cope. Recruitment of Cat Motoneurons in the Absence of Homonymous Afferent Feedback. J. Neurophysiol. 86: 616-628, 2001. This study provides the first test in vivo of the hypothesis that group Ia muscle-stretch afferents aid in preventing reversals in the orderly recruitment of motoneurons. This hypothesis was tested by studying recruitment of motoneurons deprived of homonymous afferent input. Recruitment order was measured in decerebrate, paralyzed cats from dual intra-axonal records obtained simultaneously from pairs of medial gastrocnemius (MG) motoneurons. Pairs of MG motor axons were recruited in eight separate trials of the reflex discharge evoked by stimulation of the caudal cutaneous sural (CCS) nerve. Some reports suggest that reflex recruitment by this cutaneous input should bias recruitment against order by the size principle in which the axon with the slower conduction velocity (CV) in a pair is recruited to fire before the faster CV axon. Recruitment was studied in three groups of cats: ones with the MG nerve intact and untreated (UNTREATED); ones with the MG nerve cut (CUT); and ones with the MG nerve cut and bathed at its proximal end in lidocaine solution (CUT+). The failure of electrical stimulation to initiate a dorsal root volley and the absence of action potentials in MG afferents demonstrated the effective elimination of afferent feedback in the CUT+ group. Recruitment order by the size principle predominated and was not statistically distinguishable among the three groups. The percentage of pairs recruited in reverse order of the size principle was actually smaller in the CUT+ group (6%) than in CUT (15%) or UNTREATED (19%) groups. Thus homonymous afferent feedback is not necessary to prevent recruitment reversal. However, removing homonymous afferent input did result in the expression of inconsistency in order, i.e., switches in recruitment sequence from one trial to the next, for more axon pairs in the CUT+ group (33%) than for the other groups combined (13%). Increased inconsistency in the absence of increased reversal of recruitment order was approximated in computer simulations by increasing time-varying fluctuations in synaptic drive to motoneurons and could not be reproduced simply by deleting synaptic current from group Ia homonymous afferents, regardless of how that current was distributed to the motoneurons. These findings reject the hypothesis that synaptic input from homonymous group Ia afferents is necessary to prevent recruitment reversals, and they are consistent with the assertion that recruitment order is established predominantly by properties intrinsic to motoneurons.
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INTRODUCTION |
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A stereotypical sequence of
activation is observed among the motor units that are grouped together
in an ensemble (Cope and Sokoloff 1999). The member
motor units follow one another in progression, for example, from the
weaker to the stronger and from the slower to the faster contracting
units (Binder et al. 1996
; Burke 1981a
; Cope and Clark 1995
; Henneman and Mendell
1981
; Stuart and Enoka 1983
). This recruitment
order, named the size principle (Henneman et al. 1965a
),
must emerge from systematic variation in the integration of synaptic
input by the motoneuron component of motor units. However, the relative
importance of the various pre- and postsynaptic contributors to
recruitment order remains unclear despite extensive study and
discussion (Binder et al. 1996
; Burke
1981b
; Cope and Pinter 1995
; Pinter
1990
).
Recruitment order depends to some extent on properties intrinsic to
motoneurons. The most persuasive evidence comes from behavioral studies
demonstrating that motor units recruited into activity are recruited in
the same order by a wide variety of synaptic inputs (Henneman et
al. 1965b; Somjen et al. 1965
; reviewed by Henneman and Mendell 1981
). For example, motor units
belonging to the medial gastrocnemius (MG) muscle in decerebrate cats
are recruited in the same sequence when activated in muscle stretch reflexes as they are when activated in a cutaneous reflex (Clark et al. 1993
; Cope and Clark 1991
). The common
element underlying this conforming behavior in the face of dissimilar
synaptic inputs is the motoneuron itself. Exactly which combination of
intrinsic properties might establish the hierarchy in motoneuron
excitability, whether the motoneuron's physical size, voltage
threshold, and/or membrane resistivity, has not been definitively
established (reviewed by Binder et al. 1996
;
Burke 1981a
; Cope and Pinter 1995
;
Pinter 1990
). Nonetheless, biophysical studies of
barbiturate-anesthetized cats demonstrate that the intrinsic
excitability of motoneurons, measured as current threshold, does
covary, although imperfectly, with those motor unit properties that
predict recruitment order (e.g., axonal conduction velocity and tetanic
force) (Fleshman et al. 1981
; Gustafsson and
Pinter 1984
). The inference drawn from these kinds of
correlations is that orderly recruitment traces back, at least in part,
to variation in the intrinsic excitability of motoneurons.
It is also evident that synaptic input has an important role in the
recruitment process. First, synaptic input is required for recruitment
and determines which motoneurons are selected into activity
(Cope and Sokoloff 1999). Second, synaptic input has the potential to reverse the usual order in which motoneurons are
recruited (Clamann et al. 1983
; Davies et al.
1993
; Masakado et al. 1991
; Nielsen and
Kagamihara 1993
). For example, Garnett and Stephens
(1980)
reported that the order in which motor units in the
human hand are recruited during voluntary contractions can be reversed
by prolonged electrical stimulation of the skin. The question addressed
in the present study is whether there is a third role, one in which
synaptic input actually contributes to establishing or preserving
recruitment order.
Results of computer simulations reported by Heckman and Binder
(1993) provide an assessment of the relative contributions of
intrinsic motoneuron properties and synaptic input to orderly recruitment. These investigators developed a computer model using data
collected from MG motoneurons in barbiturate-anesthetized cats to test
how synaptic current from different afferent sources influences
recruitment order. Synaptic current from homonymous group Ia afferents
was distributed among MG motoneurons such that motoneurons with low
current threshold received greater excitatory current than those with
higher thresholds (Heckman and Binder 1988
). When
introduced into the model, synaptic input from Ia afferents expanded
the range of recruitment thresholds and reinforced recruitment order by
the size principle. By contrast, synaptic current from the rubrospinal
tract compressed the range in recruitment threshold by distributing
excitation more strongly to motoneurons with intrinsically high
thresholds than to motoneurons with lower thresholds (Powers et
al. 1993
). In the model, the rubrospinal input increased the
number of reversals in recruitment order, but the addition of group Ia
input counteracted this effect and sharply reduced the incidence of
recruitment reversals. Based on these findings, Heckman and
Binder (1993)
hypothesized that "... one major role of the
monosynaptic Ia afferent system is to preserve orderly recruitment
across a wide variety of input combinations ..." (see also
Grimby and Hannerz 1968
, 1976
; Harrison and
Taylor 1981
; Heckman and Binder 1990
;
Stein and Bertoldi 1981
). The present study tests this
hypothesis with data collected in vivo from the cat.
One test of this hypothesis is afforded by studying the recruitment
order of motoneurons in the reflex initiated by stimulation of the
caudal cutaneous sural (CCS) nerve in the decerebrate cat. Sural nerve
stimulation, while able to differentially alter ongoing firing of MG
motoneurons (Kanda et al. 1977), fails to disturb the
usual sequence of recruitment order (Clark et al. 1993
;
Cope and Clark 1991
). This failure is surprising given
evidence that sural nerve input is distributed to MG motoneurons in
much the same manner as that described above for the rubrospinal input (Burke et al. 1970
; Pinter et al. 1982
;
however see LaBella et al. 1989
). One possible
explanation for this surprising result (Binder et al.
1996
) is that Ia synaptic activity, which is generally present
in intact animals and particularly high in decerebrate cats
(Matthews 1972
), acts to suppress recruitment reversals
just as in the simulations and in accord with the hypothesis of
Heckman and Binder (1993)
. This possibility was tested
here in decerebrate cats for MG motoneurons recruited by sural nerve
stimulation under the condition in which the MG nerve was cut and
treated with lidocaine. This nerve treatment was found to completely
eliminate homonymous afferent feedback but did not reduce the
proportion of motoneuron pairs recruited in order from low to high
axonal conduction velocity (CV), as predicted by the size principle and
found with the MG nerve intact. This finding demonstrates that the
basic structure of orderly recruitment does not rely on homonymous
group Ia afferent input. However, the increased number of pairs that
demonstrate trial-to-trial switches in recruitment order suggests a
role for homonymous afferents in stabilizing motoneuron excitability.
Portions of these results were presented previously in abstract form
(Haftel et al. 1997
, 1998
).
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METHODS |
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Surgical preparation
Experiments were performed on 17 male and female cats (2.5-5
kg) as approved by the Emory University Institutional Animal Care and
Use Committee. The surgical and recording procedures briefly described
here were similar to those detailed in previous reports from this
laboratory (e.g., Cope and Clark 1991; Dacko et
al. 1996
). Animals were anesthetized throughout surgery by a
gaseous mixture of halothane in 1:1 O2 and
NO2, with the halothane level adjusted between 1 and 2.5% as required to completely suppress withdrawal reflexes. The
volume and rate of artificial respiration were adjusted to maintain
end-tidal CO2 between 3 and 4%. Mean blood
pressure was monitored via carotid artery catheter, and maintained
above 70 mmHg as needed either by intravenous infusion of Ringer
solution or, on a few occasions, by a sympathomimetic amine (Aramine).
Radiant heat was adjusted to maintain rectal temperature at 37°C.
Laminectomy enabled recording from ventral or dorsal roots in spinal segments S1 or L7, while dissection of the left hindlimb enabled stimulation and/or recording from the medial gastrocnemius muscle and nerve and the caudal cutaneous sural nerve. The cat was then fixed in a rigid frame to permit stable neural recording. The hip and knee angles were fixed at 140° each and the ankle at 90°. The MG tendon of insertion was cut and attached through a force transducer to a servomotor used to hold the muscle at a length producing 100 g passive tension. The MG nerve (intact or central cut end, see following section), as well as the CCS nerve (intact) were positioned on stimulating electrodes near the popliteal fossa. Exposed tissues were covered in warm (37°C) mineral oil.
Following decerebration by removal of all brain tissue rostral to intercollicular transection of the brain stem, gaseous anesthesia was discontinued to permit reflex activation of motoneurons as described in the following text. To assist with recording stability, cats were paralyzed by intravenous infusion of pancuronium bromide (0.04 mg/kg). Cats were killed by barbiturate overdose at the end of the recording session.
Nerve treatment
The primary goal of this study was to test the dependence of recruitment order on homonymous afferent input. This goal was accomplished by comparing data collected from 17 cats in which the MG nerve was subjected to one, and in some cases, more than one of the following three acute treatments. In one treatment group (UNTREATED), data were collected from 10 cats with the MG nerve intact and untreated. In a second group (CUT), data were sampled with the MG nerve cut in the popliteal fossa during the terminal experiment. These data were collected from a total of 11 cats, 9 of which contributed data to both UNTREATED and CUT groups, being studied both before and after nerve cut. In a third treatment group (CUT+), the MG nerve was cut as just described, and the central end was drawn into the tip of a suction electrode containing a dilute solution of the fast sodium channel blocker, lidocaine (2% in isotonic saline, pH = 6.9). This condition was studied in six cats, including one examined both before and after the nerve was cut and treated with lidocaine. These three treatments proved the most practical means of studying the dependence of recruitment order on homonymous afferent input under the conditions of these experiments. Early attempts to reversibly block action potential conduction in the intact MG nerve with lidocaine proved impractical under these conditions in which recording time is limited because blockade was slow to take effect and to reverse.
Recording and stimulation procedures
Action potentials were recorded by penetrating individual axons
with glass micropipettes (2 M K-acetate, 20-30 M) in either dorsal
or ventral roots. For the purpose of determining recruitment order and
firing rate, two motor axons were penetrated simultaneously, each by a
separate micropipette, in intact ventral roots L7
or S1 (Fig. 1).
Intra-axonal recording was also used to study the effectiveness of MG
nerve treatments in eliminating homonymous afferent activity. Afferent
axons supplying the MG muscle were penetrated by glass micropipettes in
intact dorsal roots S1 and L7. Motor or afferent axons supplying the MG
muscle were identified from action potentials evoked by stimulation of
the MG nerve. All action potential records were amplified (100 times),
filtered (0.1 Hz
10 kHz), digitized (22-35 kHz), and stored on
computer for later analysis.
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Axonal CV (in m/s) was calculated from the conduction distance and delay measured from a micropipette in the ventral (or dorsal) root to the bipolar electrode on the MG peripheral nerve. Extracellular action potentials recorded from the MG nerve were initiated by injecting suprathreshold current (50-ms pulses, 1 Hz) through the micropipette. Stimulus-triggered averages (50-100 records, digitized at 40 kHz) of the action potentials recorded extracellularly at the bipolar electrode were used to measure conduction delay off-line from stimulus onset to the peak of the extracellular action potential.
MG motoneurons were recruited in the segmental reflex initiated by
stimulation of the caudal cutaneous sural nerve. The CCS reflex was
used because it is very effective in recruiting MG motoneurons
(Hagbarth 1952; Kanda et al. 1977
;
Sherrington 1910
; Siegel et al. 1999
).
This reflex was also of interest because studies of synaptic potentials
(Burke et al. 1970
; Kanda et al. 1977
;
Pinter et al. 1982
; Powers and Binder
1985
; but see LaBella et al. 1989
) have
suggested that sural reflex pathways might recruit motoneurons in an
order reversed from that predicted by the size principle. The CCS
reflex was useful therefore in testing the hypothesis that input from
MG afferents prevents reversals of recruitment order. The reflex was
evoked by stimulation of the CCS nerve electrically (40-µs pulse
duration, 100 Hz) at strengths incremented manually and rapidly
(typically within 1-2 s) to levels that recruited both MG motor axons
under study. The stimulus was repeated until both MG motor axons in a
pair were recruited to fire action potentials in eight separate
stimulus trials. Trials were separated by
30 s to minimize the
possible effects of activation history on the CCS. Repetition of the
stimulus permitted determination of the stability of recruitment order,
and eight trials were selected because this number was generally
obtainable before axonal recording quality deteriorated. Whenever
possible, motor axons were also recruited by firm pinch applied by
rat-toothed forceps to the CCS receptive field on the lateral aspect of
the ipsilateral ankle. Skin pinch was used to compare recruitment order
in response to electrical versus natural stimulation. Pinch trials were
also used to produce action potential trains from which motor axon firing rate could be measured without the contamination by stimulus entrainment that was often observed with electrical stimulation.
Data analysis
Recruitment order was determined from the sequence in which
paired axons began firing action potentials (Fig. 1). All axon pairs
were categorized by the consistency of their recruitment behavior over
all eight recruitment trials. Pairs in which recruitment order was the
same across all eight trials were labeled consistent; pairs exhibiting
inter-trial variation were labeled inconsistent. Among pairs in the
consistent category, recruitment order was designated either in accord
with the size principle, when the axon firing first had the slower CV,
or in reverse order, when the axon firing first had the faster CV.
Pairs in which axonal CV differed by 2 m/s were not reliably
distinguishable by this property, owing to variation of
1 m/s in
repeated measures for individual axons. Therefore those pairs were
excluded from further examination.
In addition to firing sequence, firing rate was measured from those
pairs in which both motor axons fired 10 or more action potentials in
response to each of three separate trials of skin pinch. The mean
firing rate was calculated and compared between axons during the time
in which the axons were simultaneously active. The purpose was to
estimate the organization of synaptic excitation from the CCS pathway
by observing the relative firing rates in each member of a motoneuron
pair. Since doublet firing (inter-spike intervals of 10 ms)
(Nelson and Burke 1967
) is thought to originate from a
postsynaptic mechanism (Bawa and Calancie 1983
;
Spielmann et al. 1993
; Zajac and Young
1980
), the doublets that were observed in some motor axons were
discarded from calculation of mean firing rates.
Statistical analysis
The effects of homonymous afferent input on motoneuron behavior
were tested statistically by comparing pooled data from each of the
three treatment conditions of the MG nerve: UNTREATED, CUT, and CUT+.
Recruitment data were examined using the G test (log
likelihood ratio test) applied in tests of goodness-of-fit and in tests
of independence (Sokal and Rohlf 1995). The
goodness-of-fit test was used to determine whether the observed
recruitment order was distinguishable from a random order. The
G test of independence was used to test for differences in
the observed frequency of pairs recruited according to the size
principle among the three animal groups.
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RESULTS |
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Eliminating homonymous afferent feedback
The present study was designed to reduce or eliminate homonymous afferent feedback to MG motoneurons to test the hypothesis that motoneuron recruitment order depends upon this feedback. Elimination was achieved by cutting the MG nerve in the periphery and treating the central cut end with lidocaine. Intra-axonal recording from dorsal roots in one CUT+ cat showed that 24/24 MG afferents within the group I range of axonal CV (>72 m/s) and sampled within 90 min of lidocaine application were silent, exhibiting no occurrences of spontaneous action potentials. In addition, dorsal root volleys could not be evoked by electrical stimulation of the cut and lidocaine-treated nerve ending at strengths exceeding five times the threshold determined prior to lidocaine treatment. The re-emergence of an evoked dorsal root volley, typically 1-3 h after treatment, was taken as evidence that the action potential blockade was wearing off, and the recruitment study was discontinued until replenishing the lidocaine solution re-established complete blockade of the dorsal root volley. These procedures enabled study of motoneuron recruitment in the absence of feedback from homonymous afferents.
Under the condition in which the MG nerve was cut but not treated with
lidocaine, spontaneous activity was observed in the intra-axonal
records taken from several MG afferents. Spontaneous discharge in
axotomized afferents occurring beyond the brief period of injury
discharge has been reported by others (reviewed by Devor 1995; see also Seburn et al. 1999
). In the
present study, 21/47 (45%) MG afferents sampled from three cats fired
spontaneously >5 min after cutting the MG nerve. In comparison,
ongoing firing was observed in 12/45 (27%) group I MG afferents in the
same three cats with the MG muscle held at a slackened length before
the MG nerve was cut (cf. Botterman and Eldred 1982
).
Spontaneous activity was observed in some afferents up to the longest
postcut duration examined, ca. 7 h, a period that extends through
the typical duration of a recruitment order study. The spontaneous discharge took the form of either high-frequency bursts or steady firing rates. In the case of steady firing, rates observed in the CUT
condition [34 ± 24 (SD) pps] were not significantly different (P > 0.05, Student's t-test for
independent samples) than for UNTREATED Ia fibers with the MG muscle
held either at 100 g passive tension (42 ± 48 pps,
n = 21) or at a slack length (34 ± 43 pps). These
findings established that simply cutting the MG nerve is not effective
in eliminating group I homonymous afferent input to motoneurons.
Nonetheless data from this CUT treatment group proved valuable for
distinguishing the effects of cutting motor axons from the effects of
eliminating afferent feedback.
Recruitment behavior
Axon pairs expressed one of three kinds of recruitment order. Order was either consistent across all eight trials, with either the low CV motor axon or the high CV motor axon recruited first, or inconsistent across trials, exhibiting at least one trial in which order switched. Table 1 lists the proportion of units falling into these three categories. Within each treatment group, the distribution of axon pairs across recruitment categories was significantly different from a random model in which percentages were distributed 33:33:33% (P < 0.005, G test). The nonrandom distribution that was observed reflects the majority of axon pairs that were consistently recruited from low-to-high CV and therefore in accord with the size principle in all three treatment groups. Two additional points of primary importance to the present study are apparent in Table 1. First, eliminating homonymous afferent input did not increase the number of recruitment reversals, as can be seen for the CUT+ group in which the percentage of axons recruited from high-to-low CV (6%) was numerically smaller than for the other two groups (19 and 15%). Second, eliminating homonymous afferent input yielded a substantial percentage (33%) of axon pairs expressing inconsistency in recruitment order. This increase in the proportion of axon pairs expressing inconsistency in the CUT+ group was associated with decreases in both categories of consistent order. Table 1 also shows that cutting the peripheral nerve alone, without lidocaine, had no detectable effect on recruitment behavior; UNTREATED and CUT groups were not significantly different.
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Consistent recruitment order
Figure 2 illustrates
the recruitment order measured for pairs of MG motor axons sampled in
each of the three treatment groups. Only those axon pairs exhibiting
consistent order in all eight recruitment trials are presented; axon
pairs expressing inconsistency are considered in the next section.
Figure 2A for UNTREATED motor axons replicates earlier
findings (Clark et al. 1993; Cope and Clark
1991
) in showing that recruitment order is strongly biased to
proceed from slower to faster CV motor axons during sural nerve reflexes. Data from two axon pairs in the UNTREATED group (both from
the same cat) fall conspicuously below the line of identity in Fig.
2A, the result of axons with relatively slow CV (
65 m/s) being recruited after axons with much faster CV (
91 m/s). Reversals in recruitment order of this magnitude are rarely observed in this
laboratory (see also Kanda and Desmedt 1983
;
Stein and Bertoldi 1981
), although preferential
activation of fast over slow CV axons on cutaneous stimulation has been
emphasized by others (Garnett and Stephens 1980
;
Kanda et al. 1977
; Nielsen and Kagamihara
1993
).
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The tendency observed in the UNTREATED group for the first recruited
axon in a pair to have the lower CV was also observed for samples taken
from CUT (Fig. 2B) and CUT+ groups (Fig. 2C). The
bias toward recruitment order from low-to-high CV was significantly different from a random recruitment order for each of the three treatment groups (P < 0.005; G test for
goodness of fit). For the UNTREATED sample, the proportion of pairs
recruited in order from low-to-high CV (33/42; 79%) was similar to the
proportion of 30/36 (83%) reported earlier by this lab
(Sokoloff et al. 1999). Most pertinent to the present
study, comparison of data from the three treatment groups revealed no
significant differences in the frequencies of axon pairs recruited in
order from low-to-high CV (P > 0.1; G test
of independence). These findings demonstrate that eliminating MG
afferent feedback was not sufficient to increase the proportion of MG
motoneurons consistently recruited in reverse order of the size principle.
Further inspection of Fig. 2 shows that the group samples are
comparable with respect to axonal CV. The ranges in CV overlap extensively and span 40 m/s, which is a large portion of the reported
CV range (Zengel et al. 1985
; cf. McDonagh et al.
1980
). Note also the similarity in CV range for those axons
sampled in each group that were not recruitable by sural nerve
stimulation in these experiments (Fig. 2,
). However, closer
inspection of Fig. 2 reveals that the CV range for axon pairs in the
UNTREATED group exceeded that for the other two groups. Taking this
difference into account by comparing treatment groups over the same
range in CV did not alter the outcome obtained in comparison of the complete data sets. This conclusion is supported by Fig. 2A
wherein the limits in CV range taken from the CUT+ group (Fig.
2C) are superimposed as - - - on data taken from the
UNTREATED group. Statistical comparison of the proportions of axons
recruited in order from low-to-high CV over this restricted range in CV
also revealed no significant differences among the three groups
(0.25 > P > 0.10; G test of independence).
Recruitment order was also assessed whenever both axons in a pair
could be recruited by skin pinch applied to the sural receptive field.
For all pairs that were recruited in consistent order over multiple
trials of sural nerve electrical stimulation, skin pinch invariably
yielded the same order. This was observed for 6/6 axon pairs in the
UNTREATED group and 17/17 axon pairs in the CUT+ group (no pairs were
tested in the CUT group). This finding establishes that our
observations on recruitment order are not artifacts of electrical
stimulation. It is also consistent with earlier observations from this
laboratory (Cope and Clark 1991) that recruitment order does not depend on the strength of electrical stimulation of the sural
nerve, which varied across trials and across pairs but which was not
monitored in these experiments.
Inconsistent recruitment order
Some axon pairs in each group exhibited inconsistency in
recruitment order over eight trials of sural nerve stimulation. The inter-trial variation in order gave no evidence of history dependence, i.e., there was no tendency for switches to occur in relation to trial
number. Neither was there any tendency for inconsistencies to increase
or decrease over the course of an experiment. Figure 3 shows the extent of inconsistency for
all pairs that expressed switches in recruitment order. The percentage
of the total sample for the CUT+ group (33% or 22/67 pairs) was
significantly larger (P = 0.0021;
2 test) than for the UNTREATED and CUT groups
combined (13% or 12/94 pairs). Also, 11/22 pairs in the CUT+ group
exhibited recruitment inconsistencies with order ratios of 3:5 or 4:4
trials, while only 3/12 pairs in the UNTREATED and CUT groups combined
had this degree of variability in order. These findings demonstrate
that removing homonymous afferent input promotes recruitment
instability.
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CV was not significantly different for axon pairs in the CUT+ group that exhibited inconsistent versus consistent recruitment order (93.0 ± 10.4 m/s, n = 44 vs. 90.7 ± 9.4 m/s, n = 90; P > 0.1, Kolmogorov-Smirnov test; P = 0.21, Student's t-test for independent samples). In addition, Fig. 4 shows that inconsistent recruitment order was neither restricted to nor uniformly expressed by pairs with similar CV. For example, 26% (7/27) of the pairs for which the difference in CV was greater than or equal to 10 m/s expressed inconsistent order. For the remaining pairs with CV difference <10 m/s, 37% (15/40) or only ~1/3 expressed inconsistency. These results give no support to the possibility that only those axon pairs for which recruitment thresholds were similar, as judged by similar CV, prior to the removal of homonymous afferent input express greater variability in order.
|
The effect of inconsistent recruitment on our assessment of the overall
tendency of the MG population to express either size-ordered or
-reversed recruitment was evaluated as follows. Recruitment order was
assigned to the 28 pairs from all three treatment groups for which
either the low or the high CV axon in a pair was recruited first in a
simple majority of trials (5/8 trials; Fig. 3). Six pairs could not
be assigned and were excluded from further analysis because order and
reversed order were expressed in equal numbers of trials (4:4). When
combined with data taken from the consistent pairs (Table 1), the
frequency of pairs expressing recruitment order from low-to-high CV was
78% (36/46), 81% (38/47), and 87% (54/62), respectively for the
UNTREATED, CUT, and CUT+ groups. Statistical analysis of these
frequencies yields the same result as the previous analysis for the
subset of axon pairs selected for consistency (Table 1), namely that
all groups exhibited recruitment order that was significantly different
from random (P < 0.01) but not significantly different
from one another (P > 0.05). These observations
demonstrate that whereas removal of homonymous afferent input increased
the proportion of motor axons expressing inconsistency, it did not
increase the incidence of reversed order.
Distribution of sural excitation among MG motoneurons
The expected increase in frequency of pairs exhibiting recruitment
reversals following the elimination of homonymous afferent input was
based on the suggestion that sural reflex pathways have the potential
to reverse recruitment order (Heckman and Binder 1993;
Kanda et al. 1977
). However, given the discrepancy in
findings on the distribution of sural excitation onto MG motoneurons
(Clark et al. 1993
; Heckman et al. 1992
;
LaBella et al. 1989
), it seemed necessary to estimate
the distribution of sural input under the conditions of these
experiments. This estimation was made from the simultaneous repetitive
firing evoked in both motor axons of a pair in response to sural
stimuli. An advantage of this pairwise estimation technique is that
firing is measured simultaneously from two motor axons in response to
the identical sural nerve stimulus.
Figure 5A illustrates the mean firing rates for those pairs driven by skin pinch to fire repetitively for a minimum of 10 spikes in each of three stimulus trials for pairs sampled from the CUT+ group. A clear tendency appears for the axon with faster CV to fire at a higher mean rate than the axon with slower CV in 7/8 pairs. Among these seven pairs, the increase in mean firing rate between member units of each pair ranged from 7 to 39 pps. This finding suggests that in the absence of homonymous afferent feedback, the sural reflex pathway distributes excitation more strongly onto fast CV than onto slow CV motoneurons and therefore might act to compress the range of recruitment threshold (see INTRODUCTION). If this tendency resulted solely from differences in intrinsic excitability of faster versus slower CV motoneurons rather than from differences in synaptic drive, then this same tendency for the faster CV axon to fire faster should occur regardless of the source of synaptic excitation. To the contrary, Fig. 5C shows a very different pattern, one in which stretch of the MG muscle resulted in slower mean firing rates in the faster CV motoneuron for 5/7 pairs. This result lends further support for the utility of this means of estimating the distribution of synaptic input from relative firing rates. Interestingly, the differential effects of skin pinch were also less regular with the MG nerve intact (Fig. 5B). In this group, firing rate was faster (2-21 pps) in 5/9 pairs, slower in 3/9 pairs (6-15 pps), and did not differ in 1 pair, for the faster versus the slower CV axon in each pair. This finding suggests that the distribution of synaptic excitation from the sural nerve onto MG motoneurons is modified by MG afferents.
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DISCUSSION |
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The present study provides the first direct test of the hypothesis
that synaptic current from homonymous group Ia muscle afferents assists
in establishing orderly recruitment among -motoneurons. The role of
muscle stretch afferents was tested indirectly in a study by
Henneman et al. (1965a)
in which activity in muscle spindle afferents was presumably reduced as a consequence of
eliminating gamma motoneuron drive to spindles by cutting ventral
roots. No change in recruitment sequence was observed under this
condition. By contrast, some evidence was obtained for reversals among
motor units recruited volitionally in human subjects in whom afferent impulses were blocked from reaching the spinal cord either by nerve
compression or by lidocaine injection (Grimby and Hannerz 1968
,
1976
). However, the experimental procedures were acknowledged to leave uncertainty about which afferents were blocked and to what
extent. In the present study, input to MG motoneurons from homonymous
afferents including group I afferents was verifiably blocked, thereby
permitting definitive conclusion that this input is not essential to
the basic structure of orderly recruitment. On elimination of
homonymous afferent input, most MG motor axon pairs were recruited in a
consistent, orderly manner in accordance with the size principle, such
that the lower CV axon of the pair was recruited first. There were
exceptions to this order, but these size principle violations were no
more frequent than with afferent input intact. Elimination of
homonymous afferent input was not without effect, however, as evidenced
by increased variability in recruitment order. In sum, we find that
homonymous afferent input does not suppress consistent reversals of
recruitment order as predicted, but its presence does check recruitment instability.
Potential mechanisms for changes in recruitment behavior
Removal of homonymous afferent feedback produced a threefold increase in the proportion of axon pairs exhibiting inter-trial variation in recruitment order. This increase occurred together with small decreases in frequency in both categories of consistent recruitment, i.e., order as well as reverse order of the size principle. None of these effects was attributable to injury sustained by the MG motor axons since cutting the MG nerve alone did not alter the normal recruitment pattern (Table 1). We have found no previous reports that lidocaine applied to the MG nerve in the periphery acts retrogradely on motoneurons to alter their central excitability. The possibility of a retrograde effect seems unlikely because inconsistent recruitment order occurred as frequently within hours after lidocaine treatment as it did later when potential retrograde effects might have been expressed. We conclude, therefore, that the recruitment instability is caused by the elimination of homonymous afferent feedback to the spinal cord.
To assist in identifying the plausible mechanism(s) by which
elimination of afferent feedback produces inconsistency in recruitment order, we adapted the computer simulation of Heckman and Binder (1993) to perform repeated recruitment trials following
procedures of the present study (see APPENDIX). Recruitment
of MG motoneurons was achieved by activating synaptic currents modeled
after rubrospinal inputs. Effective synaptic current from this input is
much greater in the least excitable MG motoneurons than in the more
excitable ones (Powers et al. 1993
), resulting in a
strong compression of the recruitment threshold range across the MG
motor nucleus. This compression is thought to be similar to that
produced by sural input (Binder et al. 1996
;
Heckman and Binder 1993
).
Figure 6 illustrates the observed and
simulated recruitment patterns under a variety of conditions. In the
presence of homonymous Ia feedback, there is good correspondence
between observed and simulated data (Fig. 6, and
, respectively)
in the percentages of axon pairs exhibiting size principle order,
reverse order, and inconsistent order. This finding for recruitment
obtained experimentally with sural input and simulated with rubrospinal input is consistent with the assertion that these inputs are similarly distributed across MG motoneurons (Burke et al. 1970
).
Evidence that sural nerve input resembles rubrospinal input in
compressing the recruitment threshold range is also given by our
confirmation of one earlier report (Kanda et al. 1977
)
that MG motor axons with faster CV fire faster than those with slower
CV in sural nerve reflexes (Fig. 5). Most importantly the model
simulates the normally observed pattern of recruitment by sural nerve
input. From this position, we determined whether removal of homonymous Ia afferent input from the model could reproduce the effects of removing homonymous afferent input on recruitment behavior in vivo.
Figure 6 shows that removal of Ia input in the model was unable to
yield the observed result. With Ia input modeled to expand recruitment
range as it does in the pentobarbital sodium (Nembutal)-anesthetized
cat (Heckman and Binder 1988
), its removal dramatically
increased consistent reversals and had little effect on recruitment
inconsistency (Fig. 6,
). This was not observed in the decerebrate
cat (Fig. 6,
).
|
A recent report calls for additional examination of the discrepancy
just described between simulation and observation. Lee and
Heckman (2000) report that for the decerebrate cat, effective synaptic current from group Ia afferents increases together
with motoneuron input conductance, a tendency that is the reverse of that observed in Nembutal-anesthetized cats (Heckman and Binder 1988
). This distribution of effective synaptic current in
decerebrate cats appears to involve amplification of the synaptic
current, perhaps by voltage-sensitive conductances in MG motoneurons.
However, Lee and Heckman (2000)
also report that
amplification in the high-input conductance cells begins at more
depolarized membrane potentials and therefore later in time as the
membrane potential approaches threshold than in the low input
conductance motoneurons. Thus the magnitude versus the onset of
amplification presents competing influences on recruitment order,
thereby leading to uncertainty about the ultimate effect of
amplification on order. Notwithstanding this uncertainty, we went on to
simulate the effect on recruitment order of Ia input distributed among
MG motoneurons so as to compress the range in recruitment threshold.
Similar to the result obtained upon removal of homonymous afferent
input in the decerebrate cat, removal of Ia input in the simulation did
not yield an increase in recruitment reversals. Unlike the result
observed in vivo, however, the incidence of inconsistent recruitment
order did not change in the simulation. These results demonstrate that
regardless of how Ia input is distributed among MG motoneurons, whether
it compresses or expands the threshold range, eliminating Ia input cannot reproduce the full range of effects observed in vivo.
By contrast, the changes in recruitment pattern observed following
elimination of homonymous afferent input could be reproduced in the
model by amplifying time-varying fluctuations in synaptic drive (see
APPENDIX). Increasing the amplitude of these fluctuations in the model yields a large increase in pairs with inconsistent order
(40%) at the expense of pairs with consistent size principle and
reversed orders (Fig. 6, ). This roughly matches the observations made in the decerebrate cat following elimination of afferent input
(Fig. 6,
), suggesting that removal of homonymous afferent input
acts to increase variance in either or both motoneuron excitability and
synaptic drive. If this increased variance was uniformly distributed among MG motoneurons, then we should have observed inconsistency predominantly among motor axon pairs with similar excitability as
assessed from CV. The latter pattern was not observed, however (Fig.
4), so we suggest that increased variance is distributed unevenly among
MG motoneurons and not in relation to CV. This uneven distribution of
variance might derive from fluctuations in membrane potential,
originating pre- or postsynaptically, that are temporally uncorrelated
or unequally distributed among MG motoneurons (Gossard et al.
1994
).
Recruitment by the size principle in the sural nerve reflex
With the MG nerve intact or treated, the activation of sural
reflexes either by skin pinch or by electrical stimulation has little
effect in reversing recruitment order by the size principle (Fig. 2).
It is important to the validity of these findings, however, to
carefully consider the way in which the sural nerve was activated. Single electrical stimuli applied to the sural nerve can produce synaptic potentials that appear first as an inhibitory postsynaptic potential (IPSP) followed by an excitatory postsynaptic potential (EPSP), particularly in motoneurons with low CV (Kanda et al. 1977; Pinter et al. 1982
, Powers and
Binder 1985
). In addition, Heckman et al. (1992
,
1994
) report that the early IPSP gives way to a steady-state
EPSP during high-frequency stimulation of the sural nerve. These
observations are relevant to the present work wherein recruitment
achieved by progressively increasing stimulus strength may have allowed
time for early inhibition to give way to excitation before either
motoneuron in the pair was recruited. In this way, the potential effect
of an early IPSP on recruitment order might have been artificially
obscured. Although we cannot discount this possibility entirely, it
seems highly unlikely for the following reasons. In the present and in
previous studies from this laboratory (Clark et al.
1993
; Cope and Clark 1991
), recruitment sequence
was not sensitive either to the rate or to the strength of electrical
stimulation of the sural nerve. In some instances, we studied
recruitment by simply switching on the electrical stimulation of the
sural nerve at strengths previously determined to recruit both motor
units and found that the percentage of reversals by the size principle
of recruitment was no greater than when the units were recruited by a
ramp increase in stimulation strength. In addition, we report here that
sudden skin pinch invariably yields the same recruitment sequence as
does electrical stimulation. For these reasons, it seems reasonable to
conclude that the tendency toward recruitment order by the size
principle was not an artifact of the stimulus protocol.
Pre- and postsynaptic dependence of recruitment order revisited
Our study provides the first test of earlier assertions that group
Ia input assists in establishing recruitment order by the size
principle (Grimby and Hannerz 1968, 1976
; Heckman
and Binder 1993
; Stein and Bertoldi 1981
). The
emergence of this orderly recruitment despite increased instability
demonstrates that order among MG motoneurons is not dependent on
synaptic input from either group Ia afferents or any of the other
primary afferents in the homonymous nerve. However, it is possible that
homonymous group Ia input is not the only synaptic source acting to
expand the recruitment threshold range. For example, MG motoneurons
receive group Ia input from the lateral gastrocnemius and soleus
muscles, and this heteronymous input was not eliminated in these
studies. However, in preliminary study, we determined that recruitment inconsistency in CUT+ cats was unaltered when heteronymous group Ia
afferent input was manipulated by changing passive muscle stretch or by
applying vibration to the lateral gastrocnemius and soleus muscles. It
seems unlikely then that heteronymous stretch-sensitive afferent inputs
produce any substantial expansion of recruitment threshold range. No
afferents other than the homonymous group Ia afferents are known to
expand the recruitment threshold range, but such afferent systems
cannot be ruled out. Powers and Rymer (1988)
found that
cutting the dorsal spinal cord compressed recruitment threshold range,
and reversed recruitment order in 4/14 pairs of motoneurons. An
injury-induced change in motoneuron excitability cannot be excluded as
the basis for this effect (see discussion in Carp et al.
1991
). All considered, it remains possible that recruitment
order is disrupted as a result of cutting some afferent system that
distributes excitation onto MG motoneurons in a pattern that assists in
establishing orderly recruitment.
Our findings are entirely consistent with the view that recruitment
order is determined predominantly if not completely by intrinsic
properties of motoneurons. The intrinsic excitability of MG motoneurons
measured as rheobase current covers a 30-fold range in
Nembutal-anesthetized cats (Zengel et al. 1985). Perhaps the computer simulations used here and earlier (Heckman and
Binder 1993
) overestimated the ability of synaptic input to
reverse recruitment order because the range in intrinsic excitability
was underestimated. It is possible that threshold range is even greater
in decerebrate cats as a consequence of voltage-dependent conductances.
A motoneuron property that might expand the range of intrinsic
excitability is the persistent inward current that is activated by much
less depolarization in the most excitable motoneurons than in less excitable ones (Lee and Heckman 1998
). Whatever they may
be, the intrinsic properties of motoneurons seem most likely to account for the abundant observations (Calancie and Bawa 1990
;
Cope and Clark 1995
; Henneman and Mendell
1981
) that orderly recruitment occurs during virtually all
naturally evoked reflexes and volitional contractions, and, as shown
here, after removal of certain inputs. Synaptic inputs, by contrast,
seem to play no part in establishing recruitment order, but rather they
determine which motoneurons are selected into activity as well as the
recruitment gain (Burke 1981a
; Heckman
1994
; Kernell and Hultborn 1990
), i.e., the
number of motoneurons recruited per increment in net excitatory
synaptic drive.
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APPENDIX |
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The purpose of these simulations was to evaluate whether removal
of Ia input could account for the findings presented in the accompanying paper. Previous simulations of motoneuron recruitment (Heckman and Binder 1993) tested the role of Ia input,
but these studies did not consider the consistency of recruitment in
repeated trials for individual pairs as was done in the foregoing work.
Basic methods
Methods for the simulations were identical to those presented by
Heckman and Binder (1991, 1993
), with the exception that each
pair of recruited motoneurons was tested for recruitment order in eight
repeated trials. The pool of simulated motoneurons consisted of 100 motoneurons. The key motoneuron parameters for the present recruitment
order simulations were the threshold current for generating an action
potential (Ithres) and the CV of the axon (CV). The distribution of threshold values was closely matched to
the distribution for the cat medial gastrocnemius motoneuron pool
(modeled in Heckman and Binder 1991
based on
experimental results from Kernell and Monster 1981
). CVs
were assigned to each motoneuron with even spacing between 70 and 110 m/s, assuming a perfect correlation between
Ithres and CV. Addition of random noise (see following text) typically expanded this range to ~50-130 m/s and produced Ithres-CV
relationships with a considerable degree of scatter. The organization
of synaptic inputs was based on weighting factors derived from the
systematic studies of effective synaptic currents from Ia input and
various descending systems by Powers, Binder, and colleagues (reviewed
in Binder et al. 1996
). The synaptic current weighting
factors and the threshold currents together determined the recruitment
threshold of the motoneuron.
Techniques for specifying noise levels
Varying degrees of random noise were added to the
Ithres and CV of each motoneuron to
simulate normal biological noise. This noise was divided into two
components. The first component
(Nneuron) was meant to mimic the
biological variance inherent in the electrical properties of
motoneurons. This variance is likely caused by factors such as the
differences between motoneurons in density of voltage-sensitive channels. Nneuron thus specified the
average scatter in the relationship between
Ithres and CV. The second component of
the noise (Nsynaptic) was meant to
represent the time-varying fluctuations in membrane potential in
motoneurons due to time-varying fluctuations in their synaptic drive.
Both forms of noise had Gaussian distributions and both were added to
the Ithres and CV values via standard
Monte Carlo techniques (Heckman and Binder 1993). Each
Gaussian distribution was scaled so that three standard deviations fell
within a specified percentage of each motoneuron's standard
Ithres and CV values. For example, if
Nneuron was set to 30% for
Ithres, then a given motoneuron's
value for Ithres was randomly chosen
from a distribution in which 3 SDs encompassed a range of 0.7-1.3
times that motoneuron's standard
Ithres value.
Nneuron was usually set to 30% for
both Ithres and CV. Correlations
between Ithres and CV for
Nneuron = 30% averaged about
r = 0.6 to 0.7, which falls at the upper end of the
range seen in experimental data for correlations between these two
parameters within individual animals (see the methods section of
Lee and Heckman 1999
). For each set of eight trials, Nneuron was applied only at the start
of the set. In contrast, Nsynaptic was
reapplied for each of the eight trials to generate intertrial
variability. Values for Nsynaptic
varied between 2 and 20%.
Simulation procedures
Each simulated experiment was performed as follows. The synaptic
organization and percentages for
Nneuron and
Nsynaptic were specified. A specific
value for Ithres and CV for each of
the 100 motoneurons was set by adding the combined noise levels
specified by Nneuron and
Nsynaptic. The recruitment threshold
for each of the 100 motoneurons was calculated based on the
Ithres values (as modified by
Nneuron and
Nsynaptic) and the synaptic weighting factors for the chosen synaptic organization (Heckman and Binder 1993). Each of the motoneurons was then randomly paired with
another one with each motoneuron used in only one pair. The percentages of the 50 pairs showing normal recruitment (low CV motoneuron first)
and reversed recruitment (low CV motoneuron recruited second) were
calculated. The run was then repeated seven more times with precisely
the same pairing of motoneurons and the same synaptic organization.
However, time varying fluctuations from trial to trial were simulated
by re-adding the noise level corresponding to the
Nsynaptic to the
Ithres and CV values of the previous
trial before each new trial began. Thus the values of
Ithres and CV for each motoneuron set
in the first trial by application of both Nneuron and
Nsynaptic then varied in subsequent
trials only by the amount specified by
Nsynaptic. A new experiment consisting of eight repeated trials was initiated by selecting new values of
Ithres and CV from the Gaussian
distributions, by reapplying both
Nneuron and
Nsynaptic, and by randomly setting new
pairings between motoneurons.
Experiments were repeated 500 times for a given input organization and
noise level. The results for a set of 500 experiments were expressed in
terms of the percentage of consistent normal pairs (low CV motoneuron
recruited first in all 8 trials), the percentage of consistent
reversals (low CV motoneuron recruited second in all 8 trials) and the
percentage of inconsistent pairs (1 trial with a different
recruitment order than the others). All percentages were averages of
the values across all 500 experiments.
Organization of synaptic input
To replicate the control conditions in the experimental data,
three assumptions were made about the organization of simulated synaptic input. 1) The main excitatory drive during the
sural input generated relatively larger effective synaptic currents in
high- than low-threshold motoneurons. This input thus tended to
compress the range of recruitment thresholds set by the ~10-fold range of Ithres values (3.5-40 nA
before any noise was added) (Heckman and Binder 1993).
This assumption is supported by the larger effect of sural input on
firing rate of high-threshold units (see Fig. 5). 2) A
small, constant inhibitory bias current existed. This inhibition was
applied simply because it seemed unlikely that the sural drive was
purely excitatory. While much of the inhibition during the sural input
fades within the first 50 ms of steady stimulation (Heckman et
al. 1994
), recruitment of units in the present study occurred
near the onset of sural input, where inhibition is still likely to be
important. In addition, there may exist some tonic baseline inhibition
in the decerebrate due, for example, to tonic firing in antagonist Ia
afferents. 3) All motoneurons received a steady bias of
excitatory input from Ia afferents. This of course was the main
assumption driving the experimental studies (see
INTRODUCTION). The sensitivity of the simulations to these
three assumptions was evaluated (see following text). The amplitude of
the inhibitory bias was set to 1 nA and the excitatory bias from Ia
afferents was set to 2 nA. The inhibition was given a uniform
distribution for all motoneurons (the inhibitory systems studied thus
far have uniform distributions) (Binder et al. 1996
). As
pointed out in the INTRODUCTION, the Ia input is
distributed preferentially to low-threshold units and thus tends to
expand the range of recruitment thresholds (Heckman and Binder
1988
).
Simulation results
The main results are shown in Fig. 6 in the
DISCUSSION. An accurate recreation of the control data was
achieved with Nneuron set to 30%,
Nsynaptic set to 4%, and the sural
synaptic drive distributed according to the weighting factors used for
the rubrospinal system in Heckman and Binder (1993). As
presented in DISCUSSION, removal of Ia input without
altering Nneuron and
Nsynaptic did not replicate the effect
of removing the homonymous input (cf. Fig. 6,
and
). A good
match to removal of homonymous input was achieved when
Nsynaptic was increased from 4 to 12%
(Ia input was again eliminated;
Nneuron remained at 30%; Fig. 6,
). This replicated both facets of the removal of homonymous input in
the experimental data: slight decreases in both consistent size
principle pairs and consistent reversed pairs coupled to a large
increase for inconsistent pairs.
Sensitivity analyses for synaptic organization
The rubrospinal input is much stronger in high than
low-threshold cells (Binder et al. 1996). In the
simulations, this differential action was captured by using a ninefold
range of weighting factors (largest weights to high-threshold units,
smallest to low-threshold units) (see Heckman and Binder
1993
). Effective synaptic currents for sural input have not yet
been measured, but the assumption that the sural excitation also favors
activation of high-threshold units is reasonable (see
DISCUSSION). However, the differential sural effect may not
be as strong as for the rubrospinal excitation. We therefore
systematically simulated the effects of reducing the preferential
excitatory drive to high-threshold motoneurons by substituting
vestibulospinal excitation (which has only a twofold range of weighting
factors) for rubrospinal excitation. For the Ia input, the key issue is
whether the simulated amplitude of 2 nA exaggerates the impact of the
tonic firing of Ia afferents in the homonymous nerve in the decerebrate
preparation used in this study. The amplitude of Ia input used in the
simulation was based on activation by tendon vibration in the
pentobarbital anesthetized preparation (Heckman and Binder
1988
), which likely generated average firing rates of 180 Hz in
Ia afferents. The lower firing rates of tonically active Ia afferents
(see RESULTS) are at least somewhat offset by dendritic
amplification of Ia actions that are present in the decerebrate
(Lee and Heckman 2000
; Prather et al.
2001
). We tested the effect of both lowering and raising the
amplitude of the Ia bias current. Finally, we also evaluated the effect
of lowering and raising the inhibitory bias currents. None of these
changes in input organization altered the main result of Fig. 6. In
general, changes in input organization, whether from different input
systems or changes in amplitudes of bias currents, impact recruitment
order by compressing or expanding the 10-fold range of recruitment
thresholds established by the intrinsic current thresholds of the
motoneurons (i.e., the differences in
Ithres in the simulation)
(Heckman and Binder 1993
). Changes in threshold range
invariably had parallel effects on the percentages of consistent
reversals and inconsistent pairs. A strong compression of the range
produced a marked increase in consistent recruitment reversals coupled
with a small increase in inconsistent pairs (this was essentially what
happened when the simulated Ia input was removed in Fig. 6). Expansion
had the opposite effects. Neither change mimicked the experimental
results for removing homonymous input in which consistent recruitment
reversals and inconsistent pairs changed in opposite directions (see
Fig. 6).
Sensitivity analyses for noise
Changes in Nsynaptic had
the expected effects: the larger the amplitude of
Nsynaptic the greater the percentage
of inconsistent pairs and the lower the percentage of both consistent
size principle pairs and consistent reversed pairs. This is exactly
what eliminating homonymous input did (Fig. 6, ). In contrast,
increases in Nneuron had inverse
effects on consistent pairs, decreasing the size principle pairs while
increasing the reversed pairs. The percentage of inconsistent pairs
increased slightly with increased
Nneuron. In other words, increasing
Nneuron acted somewhat like
compressing the range of recruitment thresholds, having parallel
effects on consistent reversals and inconsistents. Thus changes in
Nneuron could not produce the decrease
for consistent reversals and large increase for inconsistents seen in
the data and accurately simulated by changes in
Nsynaptic (Fig. 6).
One aspect of the experimental results that could not be
simulated was the result illustrated in Fig. 5, which shows
inconsistency in recruitment among motoneuron pairs expressing the full
range of differences in CV. In the simulations, there was a strong
tendency for inconsistent recruitment to occur more frequently among
pairs with close CVs. The reason for the lack of this relation in the experimental results is unclear, as one would expect it to be easier to
alter recruitment order in unit pairs with close thresholds, which
presumably have close CVs. Perhaps this discrepancy can be accounted
for by the dynamic characteristics of the synaptic noisefor example,
occasional large noise peaks that also have fast rates of rise might be
particularly effective at recruiting even a relatively high-threshold
unit out of its normal order. Obviously, dynamic phenomena cannot be
simulated using the present techniques, which assume steady conditions.
However, these dynamics would only apply to
Nsynaptic not
Nneuron because
Nneuron is only meant to capture the
variability in intrinsic differences in motoneuron properties. Thus the
basic conclusion of this subsection, that changes in
Nsynaptic but not
Nneuron could replicate the
experimental results shown in Fig. 6, still holds. Similarly, the
conclusion of the previous section, that changes in synaptic
organization alone cannot produce the experiment results of Fig. 6,
would not be altered by including dynamic properties in
Nsynaptic.
Summary of sensitivity analyses
The sensitivity analysis presented in the preceding text indicates that the simulation results presented in Fig. 6 are representative examples of a wide range of simulations with different synaptic organizations and synaptic noise amplitudes. Thus the main conclusion from Fig. 6, that increases in Nsynaptic provided the best simulation of removing homonymous input, is likely to be correct even if the specifics of the simulation did not precisely replicate biological reality.
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ACKNOWLEDGMENTS |
---|
The authors thank Dr. Robert Lee for critical review of the manuscript.
This research was supported by National Institute of Neurological Disorders and Stroke Grants NS-21023 (T. C. Cope) and NS-34382 (C. J. Heckman).
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FOOTNOTES |
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Address for reprint requests: V. K. Haftel, Dept. of Physiology, 1648 Pierce Dr., Emory University, Atlanta, GA 30322 (E-mail: valh{at}physio.emory.edu).
Received 3 November 2000; accepted in final form 16 April 2001.
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REFERENCES |
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