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The Journal of Neurophysiology Vol. 80 No. 2 August 1998, pp. 572-582
Copyright ©1998 by the American Physiological Society
Department of Physiology, Northwestern University Medical School, Evanston, Illinois 60201
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Lee, R. H. and C. J. Heckman. Bistability in spinal motoneurons in vivo: systematic variations in rhythmic firing patterns. J. Neurophysiol. 80: 572-582, 1998. In the presence of the monoamines serotonin and norepinephrine, spinal motoneurons can exhibit bistable behavior, in which a brief period of excitatory input evokes prolonged self-sustained firing. A brief inhibitory input returns the cell to the quiescent state. To determine whether motoneurons differ in their capacity for bistable behavior, intracellular recordings were obtained in the decerebrate cat preparation. To enhance the likelihood of encountering bistable behavior, the noradrenergic 
1 agonist methoxamine was applied to the ventral surface of the cord. The capacity of the cells to produce bistable behavior was assessed from the duration of self-sustained firing evoked by a brief (1.5 s) excitatory synaptic input from muscle spindle Ia afferents. About 35% (17 of 49) of the cells produced steady self-sustained firing for >3 s and were considered fully bistable. The other 32 cells (~65%) were partially bistable, with self-sustained firing lasting <3 s. Fully bistable cells tended to have lower current thresholds for spike initiation and slower axonal conduction velocities than did partially bistable cells. This suggests that fully bistable motoneurons innervate fatigue resistant muscle fibers. The frequency-current (F-I) relations of the motoneurons were characterized with slow triangular current ramps. Fully bistable cells displayed an acceleration in firing rate immediately on initiation of rhythmic firing. The F-I gain after completion of the acceleration was positive. Fully bistable cells also displayed a hysteresis in the current level for firing threshold with the ascending threshold occurring at substantially higher current level than the descending one. Additionally, these current thresholds usually were centered about zero current, so that the ascending current threshold was positive while the descending current threshold was negative. This negative offset meant that fully bistable cells could exhibit tonic firing without depolarizing injected current. Partially bistable cells exhibited very different F-I characteristics. Firing rate acceleration was just as large as in fully bistable cells but did not occur until well above the current level needed to initiate rhythmic firing. F-I gain after acceleration was negative, there was little to no hysteresis between the ascending and descending firing thresholds, and both thresholds were above the zero current level. These properties of partially bistable cells suggest their functional role is in tasks requiring relatively brief, high forces. The low thresholds of fully bistable cells mean they will be readily recruited in low force tasks like posture, where their prolonged self-sustained firing would be advantageous.
The electrical behaviors of motoneurons are subject to modification by several neuromodulators, and generally speaking, these neuromodulators tend to enhance motoneuronal excitability (reviewed in Binder et al. 1996 Preparation
Data were obtained from 14 cats (average weight ~2.5 kg). All procedures were approved by the animal care committee at Northwestern University. Initial surgical preparations were done under deep gaseous anesthesia (1.5-3.0% isoflurane in a 3:1 mixture of O2 and N2O), according to standard procedures in our lab (Heckman et al. 1994 Drug application and effects
Methoxamine, a noradrenergic Intracellular recording
Intracellular recordings were obtained with sharp microelectrodes filled with potassium citrate (IM). In all 10 experiments involving intracellular recordings, the preparation was paralyzed with gallamine triethiodide (Flaxedil; 10 mg initial dose, supplemented at regular intervals with additional doses of 1-2 mg) and artificially respired. End tidal CO2 was monitored and kept within acceptable limits by adjusting respiration rate and volume. In addition, a bilateral pneumothorax was done to enhance intracellular recording stability. Microelectrode tips were broken back under microscopic observation and control. Because of the large currents needed to evoke rhythmic firing and because some of the cells were studied using single-electrode voltage-clamp techniques (see Lee and Heckman 1998 Data analysis
DATA ACCEPTANCE CRITERIA.
The main acceptance criteria were that the amplitude of the antidromic spike exceeded 70 mV and the resting membrane potential did not vary by more than ±5 mV during the course of the data collection. However, eight cells exhibited tonic firing in the absence of any input, requiring the application of a steady hyperpolarizing current for the duration of the impalement. After compensating for the electrode resistance with the bridge balance circuit, these eight cells met the same membrane potential stationarity and spike height requirements as the other cells. Additionally, most of these cells had free running spike heights greater than the 70-mV requirement even while firing tonically at zero current. A total of 49 cells met the above stability requirements.
ASSESSMENT OF BISTABLE BEHAVIOR.
Data with sustained firing patterns generated in response to tendon vibration and injected current ramps were digitized at 5-10 kHz. Antidromic spikes were digitized at 58 kHz to allow accurate measurement of conduction time. All data were stored on removable hard disks for off-line analyses.
CONDUCTION VELOCITY AND ESTIMATION OF MOTOR UNIT TYPE.
In preparations where activity in monoaminergic axons is suppressed, rheobase is an excellent predictor of motor unit type (Zengel et al. 1985 STATISTICAL ANALYSES.
The electrical properties of fully versus partially bistable cells were compared using t-tests, assuming unequal sample variances. In addition, linear regression analyses were used to assess the relationships between variables. The significance level, alpha, was set at P = 0.05. Where results from multiple t-tests were compared (as in Table 1), we chose a conservative alpha level of 0.05/10 = 0.005.
Bistable behavior in motoneurons
All studies were carried out after application of a standardized dose of the noradrenergic
Variation in bistable behavior with motoneuron electrical properties
To test the hypothesis that motoneurons with low rheobases and conduction velocities were more likely to exhibit strong bistable behavior, we compared the duration of self-sustained firing following Ia input in each cell to its electrical properties. In pentobarbital-anesthetized preparations, rheobase is well correlated with motor unit type, with type S units having the lowest values (Fleshman et al. 1981
Frequency-current relationships
The effect of the plateau potential underlying the bistable behavior also was evaluated while systematically varying the input to the cell. Figure 3 shows the firing patterns of a fully and a partially bistable cell in response to three injected current steps of increasing amplitude. The fully bistable cell (Fig. 3A) began firing with the first step and then immediately underwent a relatively rapid acceleration in firing frequency to reach ~40 Hz. This acceleration likely was produced by the onset of the plateau potential (cf. Hounsgaard and Kiehn 1989
Rate adaptation
The tendency for the firing rate to decay in partially bistable cells (see Figs. 3B and 4E) may be related to the long-term rate adaptation seen motoneurons in deeply anesthetized preparations (see the discussion in the companion article). A significant factor in long-term rate adaptation is that higher initial firing rates are associated with greater adaptation (Kernell and Monster 1982 Threshold for sustained rhythmic firing versus rheobase
In spinal motoneurons in pentobarbital-anesthetized preparations, the threshold current for sustained rhythmic firing (referred to above as the ascending threshold for the F-I function) is usually greater than the threshold current required to generate a single spike (i.e., rheobase) (Kernell and Monster 1981
Summary
Approximately one-third of the cells in our sample could generate prolonged self-sustained firing and were considered fully bistable. This behavior resulted from a combination of the endogenous effects of tonic activity in reticulospinal serotonergic and noradrenergic axons (see further text), and the exogenous actions of the noradrenergic Methodological considerations
Previous work has established that serotonergic fibers that originate in the brain stem are tonically active in the decerebrate cat preparation (Crone et al. 1988 Motor unit type and bistable behavior
As noted in the INTRODUCTION, a capacity for long-term, self-sustained firing in type FF motoneurons does not make good functional sense because of their very poor resistance to fatigue. The finding in the present study that fully bistable cells tend to have low current thresholds and slow conduction velocities is supportive of the conclusion that these are type S and FR cells. However, current thresholds are clearly lower in our sample than in the studies that established threshold-type correlations (Bakels and Kernell 1993 Functional implications
The bulbospinal tracts that release the monoamines norepinephrine and serotonin are tonically active in the waking state (Aston-Jones et al. 1991
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
). The monoamines serotonin and norepinephrine have an especially profound effect on adult spinal motoneurons, allowing brief periods of synaptic input to generate sustained depolarizations known as plateau potentials (Conway et al. 1988; Hounsgaard and Kiehn 1989; Hounsgaard et al. 1988). Input from either synaptic activation or current injected via the microelectrode can initiate a plateau potential. This is manifest as a sudden depolarization if the cell is subthreshold or as a sudden acceleration in discharge frequency if the cell is already firing. When the input is terminated, the plateau potential can persist for long periods, allowing the cell to maintain a tonic firing rate in the absence of applied input. A brief hyperpolarizing input can eliminate this self-sustained firing and return the cell to the quiescent state. Thus the cell is said to be "bistable" because it has two stable states for the same input condition, quiescent and self-sustained firing (Hounsgaard et al. 1984). Bistable behavior has been seen in several different types of cells (e.g., Hounsgaard and Kiehn 1989; Hounsgaard et al. 1988; Lechner et al. 1996; Morisset and Nagy 1996; Rekling and Feldman 1997; Russo and Hounsgaard 1996; Zhang and Harris-Warrick 1995).
; Lee and Heckman 1996b), a phenomenon that may be linked to the well-known differences in motoneuron electrical properties (reviewed in Binder et al. 1996). Motoneurons requiring only a small amount of synaptic or injected current to reach threshold for rhythmic firing also tend to have low input conductances and slow axonal conduction velocities. These low-threshold motoneurons tend to innervate muscle fibers with slow contraction speeds and low forces but with very high resistances to fatigue. In contrast, the high-threshold motoneurons with fast conduction velocities innervate fast, high-force muscle fibers with poor fatigue resistances. Motoneurons with intermediate-valued properties are distributed in a continuum between these two extremes. This continuum of motor units usually is divided into three classes based on the differences in muscle fiber properties: type S (slow), FR (fast, fatigue resistant), and FF (fast, fatigable) (Burke et al. 1973). From a functional viewpoint, the fatigability of the motor units is a particularly important consideration for bistability in motoneurons because prolonged firing in FF motor units would rapidly lead to severe fatigue. Therefore a reasonable hypothesis is that long-term self-sustained firing is most likely to occur in motoneurons with low thresholds and slow conduction velocities, whereas it may be weak or absent in motoneurons with high-thresholds and fast conduction velocities.
; Engberg et al. 1968) and also may have tonic activity in reticulospinal noradrenergic fibers (Sastry and Sinclair 1976) (see DISCUSSION). In addition, to increase the probability that motoneurons would exhibit bistable behavior, we applied the pharmacological agent methoxamine, a noradrenergic 1 agonist (cf. Lee and Heckman 1996b). The tendency for bistable behavior was assessed by applying a short period of steady synaptic input and by measuring the relationship between discharge frequency and the amplitude of current injection via the microelectrode (i.e., the F-I relationship). Our results were consistent with the proposed hypothesis that the duration of self-sustained firing was longest in cells with slow conduction velocities and low thresholds. In addition, these same cells exhibited marked hysteresis in their F-I relations (cf. Hounsgaard et al. 1988) (D. J. Bennett, H. Hultborn, B. Fedirchuk, and M. Gorassini, unpublished data). A portion of these results has been presented in abstract form (Lee and Heckman 1996a, 1997).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). In the left hindlimb, the nerves to medial gastrocnemius (MG) and lateral gastrocnemius-soleus (LGS) muscles were isolated carefully and left in continuity. The entire Achilles tendon was attached to a muscle puller via a bone chip from the calcaneus. Before the tendon was freed, the foot was dorsiflected manually, and a small piece of suture was tied to the tendon and to the underlying shank of the lower leg. After the soleus was attached to the puller, alignment of the two threads was defined as maximum physiological length. The surgically exposed areas of the hindlimb were covered with a pool of mineral oil that was formed within the pulled-up skin flaps. A precollicular decerebration was performed by transecting the midbrain with an ophthalmic spatula and aspirating the entire forebrain. The calvarium was packed with saline-soaked cotton wool. The gaseous anesthesia then was discontinued, and the animal was allowed to breathe room air. Radiant heat was used to maintain hindlimb and core temperatures within physiological limits. At the end of the experiment, the animals were killed with a lethal dose (100 mg/kg iv) of pentobarbital sodium.
1 agonist (obtained from Sigma), was applied via a modified intrathecal method. A fine-diameter catheter (PE10 polyethylene) was slid gently under the lumbar enlargement after the dura of the cord was opened. The entry point for the catheter was at L5 and the catheter reached to approximately L6 or L7. The catheter was secured by suturing it to the pinned-out dura, and its distal end was taped to the spinal frame. Mineral oil then was applied to form a pool over the exposed spinal cord, with care being taken to avoid disturbing the CSF and saline that remained underneath the cord after the dura was cut. Thus when the drug was applied via this ventral topical method, it diffused into the CSF/saline already present under the cord.
). The animals for these four experiments were not paralyzed, and the reflexive muscle force produced by the Ia input was assessed via a strain gauge. Muscle length was set at ~10-mm short of physiological maximum.
; Engberg et al. 1968), and there also may be tonic activity in noradrenergic reticulospinal axons (see DISCUSSION). The bistability seen in this study then resulted from both noradrenergic and serotonergic effects.
), resistances of the electrodes were kept low
typically ~4-6 M
in saline before entering the cord.
), in which synaptic noise evokes spikes (Calvin 1974). Hyperpolarizing baseline currents were used to eliminate the self-sustained firing and confirm that the Ia input had a crisp offset. Next, the frequency-current (F-I) function of the cell was assessed via injection of a current waveform with a triangular shape. The rates of rise and fall were equal at 5 s each. The amplitude of the triangular-shaped current was adjusted so that each cell reached a firing rate of 
60-80 Hz. This resulted in the rate of rise varying from 4 to 8 nA/s (the F-I behaviors obtained for this range of rates were similar). In most cells, the amplitude of the triangular-shaped current was 30 nA, resulting in a rate of rise of 6 nA/s, and a steady DC bias current was used to control the peak current reached during the input. In some cells, this was followed by a series of current steps lasting 1-3 s.
30 s was allowed to elapse between each of the protocols. This was done to avoid the effects of voltage-dependent facilitation (Bennett et al., unpublished data; Svirskis and Hounsgaard 1997). This phenomenon was not quantified in our studies but was readily apparent. For example, if the current pulses to assess rheobase were applied with ~0.5-s intervals, the depolarization produced by each pulse increased and a burst of spikes often developed by the third or fourth pulse.
). However, both serotonin and norepinephrine are likely to reduce rheobase (Larkman and Kelly 1992; Lindsay and Feldman 1993; Parkis et al. 1995) (see RESULTS). In contrast, conduction velocity is unlikely to be altered. To confirm that conduction velocity remained unchanged, we monitored the latency and shape of the extracellular field produced by antidromic stimulation of the MG and LGS nerves in two experiments before intracellular data were taken. No differences were found in either parameter before, during, and for 30 min after ventral topical application of the standard dose of methoxamine. We did not measure conduction distances in our experiments, preferring to primarily rely on within-animal comparisons of conduction times in the two experiments with the largest sample sizes (n = 9 and n = 10). This analysis was supplemented with a comparison of conduction times across experiments where the conduction times within each experiment were normalized by that experiment's average. These across-experiment analyses were only carried out in experiments with data from at least two fully and two partially bistable cells. This gave a total of four experiments, the two with the largest samples and two further experiments where n = 7 and n = 4. Conduction time was measured from the difference between stimulation onset in the nerve and the initiation of the antidromic action potential above baseline.
View this table:
TABLE 1.
Comparison of F-I behaviors in fully and partially bistable cells
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
1 agonist methoxamine via the catheter placed under the lumbar cord (see METHODS). The steady monosynaptic input from Ia afferents generated by tendon vibration (1.5-s duration) was used to assess the capacity of motoneurons to generate self-sustained firing. Of the 49 cells, 17 (or ~35%) were fully bistable, i.e., they exhibited self-sustained firing for >3 s (see METHODS). Figure 1A shows typical data for a fully bistable cell. When this cell was depolarized to within ~5 mV of its threshold for steady firing (Fig. 1A, top), it responded with a high discharge frequency (~50 Hz) during the Ia input. This was followed by steady, self-sustained firing at lower rate (~20 Hz) after the Ia input ceased. In the absence of injected current (Fig. 1A, middle), the self-sustained firing only lasted ~1 s. Hyperpolarization (Fig. 1A, bottom) eliminated firing and revealed a 1.5-s Ia EPSP with a sharp onset and offset.
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FIG. 1.
Example of bistable behavior in 2 motoneurons elicited by a 1.5-s period of excitatory synaptic input from muscle spindle Ia afferents. A: fully bistable cell at 3 different holding currents (indicated by labels on left portion of the traces). At a holding current of +2 nA (top), the cell fires steadily after the end of the synaptic input for the 3 s necessary to be considered fully bistable. (Spike peaks truncated for clarity.) At a slightly lower holding current of 0 nA (middle), the cell only generates afterdischarges for ~1 s. At hyperpolarizing hold current of -8 nA (bottom), no firing is seen and the Ia input is seen to exhibit a sharp offset. B: partially bistable cell. At a holding current that is nearly at rhythmic firing threshold (7.5 nA; top), the cell produces only a few spikes after the end of the input. At lower current levels (5 nA; middle), fewer spikes are seen after the input. At 0 nA (bottom), the cell does not spike and the Ia input produces an excitatory postsynaptic potential (EPSP) with a rapid offset.
; Zengel et al. 1985). Thus a low rheobase implies a high fatigue resistance. Figure 2 illustrates the relationship between rheobase and the duration of the self-sustained firing after the Ia input. The average rheobase of the fully (
) and partially bistable cells (
) was 1.4 ± 4.1 nA and 8.8 ± 3.3 nA, respectively, and this difference was statistically significant (t-test, P < 0.000001).
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FIG. 2.
Duration of self-sustained firing versus rheobase. Data from 17 fully ( ) and 32 partially bistable () cells. All durations for fully bistable cells are shown as 3 s even though they could fire for much longer (see text). When 2 fully bistable cells had identical rheobases, 1 of the pair of symbols was slightly offset horizontally for clarity.
; Parkis et al. 1995). Consistent with this, the range of rheobases in our sample (
5 to +14 nA) is shifted downward in comparison to previous studies in pentobarbital anesthetized preparations (+3 to +30 nA) (e.g., Gustafsson and Pinter 1984), which lack neuromodulatory input form the brain stem. Therefore we assessed axonal conduction velocity for the antidromic spike, which also is correlated with motor unit type (e.g., Emonet-Denand et al. 1988) but was not altered by methoxamine (see METHODS).
0.90 (n = 9) and 0.74 (n = 10), resulting in P values of 0.0005 and 0.007, respectively. The across experiment analysis, which was based on the four experiments in which data from at least two fully and two partially bistable cells were obtained, also resulted in a significant correlation between normalized conduction time (see METHODS) and rheobase (P < 0.001). Thus the relationship between rheobase and conduction velocity seen in the pentobarbital-anesthetized preparation (e.g., Fleshman et al. 1981; Zengel et al. 1985) was preserved, suggesting that the overall range of rheobases was lowered without seriously distorting the S versus FR versus FF hierarchy.
). The subsequent two current steps gave further small increases in frequency, each coupled to a very slight degree of adaptation in firing rate during the course the 3-s step duration. The partially bistable cell shown in Fig. 3B also showed a very strong acceleration in firing due to plateau potential onset, reaching ~36 Hz during the second step. However, the subsequent adaptation was much more dramatic than in the fully bistable cell, with firing rate decreasing steadily after the peak of the acceleration. The final step increase in current elicited a small increase in firing rate in the otherwise clearly decreasing trend. Also note that steady firing existed below the current level require to evoke acceleration.
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FIG. 3.
Examples of firing rate acceleration in fully and partially bistable cells. A and B, top, firing rate (···, instantaneous firing rate; 
, moving average of 5 interspike intervals); bottom: injected current. Each step increase in current was 3 nA. A: current "stair step" input to a previously quiescent, fully bistable cell. Firing rate starts at ~18 Hz but rapidly accelerates to 40 Hz during the first 3 nA step. Subsequent steps result in small jumps in firing rate but no further acceleration. Note that the cell continues to fire after the holding current returns to 0. B: stair step current input to a partially bistable cell from a holding current of 15 nA. Cell is already firing steadily at the initial holding current. First 3 nA step causes a small increase in firing rate from to ~12 to ~16 Hz. Second step causes the firing rate to accelerate to a peak of ~36 Hz. Firing rate then immediately begins to decline. Third step causes a brief increase in the steadily decreasing firing rate.
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FIG. 4.
Frequency-current (F-I) relationships for a fully bistable cell (left) and a partially bistable cell (right). A and B: changes in membrane potential in response to a triangular injected current (10-s total duration; spikes truncated for clarity). C and D: firing frequency vs. time for data from A and B, respectively. Dotted line, instantaneous firing rate; thick solid line: smoothed firing rate (moving average of 5 interspike intervals); solid thin line: injected current. In the fully bistable cell, firing rate and threshold coincided. In the partially bistable cell, firing rate acceleration occurs ~8 nA higher than the initiation of firing. E and F: F-I plots of data in C and D, respectively. Labeled features are the behaviors used for quantitative comparisons of fully and partially bistable cells. In both types of cells, firing acceleration is manifest as a high gain region (acceleration gain). Postacceleration gain in the fully bistable cell was positive, whereas it became briefly negative in the partially bistable cell. Descending threshold occurred at a substantially lower current level than the ascending threshold in the fully bistable cell, but the 2 thresholds were similar in the partially bistable cell.
). Note also that variability in firing rate increased sharply during this phase. This is consistent with previous work showing that plateau potentials greatly increase membrane noise (Hounsgaard et al. 1988). The F-I slope on the descending phase (i.e., the descending gain) is slightly greater than the postacceleration gain (see Table 1). Firing occurs over a much wider current range on the descending phase because the descending threshold (i.e., the current at which firing ceases) did not occur until current reached a strongly hyperpolarized level (7 nA). In Fig. 4A, it is clear that the plateau potential persists beyond the end of the triangular input, producing occasional spikes as it slowly decayed during about a 5-s period (only a portion of which is shown). This threshold hysteresis was seen in all bistable cells (cf. Bennett et al., unpublished data; Hounsgaard et al. 1988), with the average difference between descending and ascending thresholds being ~6 nA (Table 1).
).
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FIG. 5.
Comparison of postacceleration gain to peak acceleration frequency for both fully and partially bistable cells. Postacceleration gain of the fully bistable cells ( ) has a slight downward trend with frequency but remains above 0 [slope = 0.03 (Hz/nA)/Hz, r = 0.49, significance of slope P = 0.12]. In contrast, the postacceleration gain of the partially bistable cells (
) can be seen to decrease sharply with frequency and is usually negative [slope = 0.31 (Hz/nA)/Hz, r = 0.75, significance of slope P < 0.001].
; Sawczuk et al. 1995). A relationship of this type was evident on the ascending phase of our triangular current inputs. The peak firing rate at the end of the high gain phase (i.e., after acceleration had run its course) was correlated negatively with the subsequent gain of the F-I function within the partially bistable group (P < 0.001; see Fig. 5). However this relationship was not significant in the fully bistable group (P = 0.12), and the slope of this relationship was much steeper for the partially bistable group than the fully bistable group despite the extensive overlap in peak frequency ranges. This suggests that the greater tendency of the partially bistable group to exhibit rate adaptation is not solely due to higher frequencies during the acceleration. The increased tendency for decay in firing rate in partially bistable cells presumably reflects the decay characteristics of the persistent inward current that produces the plateau potential (see Lee and Heckman 1998).
). In Fig. 6 the ascending (A) and descending (B) current thresholds are plotted versus rheobase. Although the partially bistable cells conform to expectation that their ascending thresholds are greater than their rheobases, the fully bistable cells have ascending thresholds that tend to be lower than their rheobases. The slope for the descending thresholdrheobase relationship is even steeper because the descending threshold in bistable cells is even lower than the ascending threshold. The probable basis for this result is that the rheobase current is too brief to activate the plateau potential. Thus if the voltage threshold for the plateau potential is lower than the voltage threshold for the action potential, rhythmic firing can commence below rheobase (see Lee and Heckman 1998).
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FIG. 6.
Comparison of currents for rhythmic firing thresholds to rheobase currents for both fully and partially bistable cells. A: ascending firing threshold vs. rheobase. - - -, regression relation (slope: 1.24; intercept: 1.23; r = 0.91; P < 1 × 10
11). Note the regression slope was somewhat >1 (), indicating that fully bistable cells tended to have an ascending threshold slightly below rheobase. B: descending firing threshold vs. rheobase (slope: 1.72; intercept: 5.78; r = 0.86; P < 1 × 109). Fully bistable cells clearly have descending thresholds below rheobase, whereas partially bistable cells have descending thresholds slightly above rheobase.
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
1 agonist methoxamine. The fully bistable cells tended to have lower conduction velocities and lower current thresholds than the partially bistable cells, which lacked the capacity for prolonged self-sustained firing. Consequently, it is likely that the fully bistable cells are type S or perhaps type FR. The limitations imposed on this conclusion by the noise in the relation between conduction velocity and motor unit type are discussed later.
). In partially bistable cells, the plateau potential was activated well above F-I threshold and then appeared to rapidly decay, resulting in negative postacceleration gain and a lack of threshold hysteresis.
; Engberg et al. 1968). In addition, it seems likely that there was some tonic activity in reticulospinal noradrenergic fibers in our preparation. Engberg et al. (1968) concluded that noradrenergic pathways did not play a significant role in decerebrate excitability, but Sastry and Sinclair (1976) found evidence for a tonic noradrenergic drive to Renshaw cells. Both of these studies were done in intercollicular decerebrate preparations. An intercollicular transection may damage the upper portion of the locus coeruleus, which is a primary source of descending noradrenergic fibers. Our studies used precollicular decerebrates, in which the locus coeruleus was likely left entirely intact. Therefore the effects of the applied methoxamine probably were superimposed on at least some endogenous release of both serotonin and norepinephrine.
).
), it is likely that the form of the F-I function will be somewhat different when synaptic current is the primary source of input. For example, Bennett et al. (unpublished data) showed that synaptic input lowers the frequency and current at which firing acceleration begins. We suspect that addition of synaptic current will have approximately equal effects on partially and fully bistable cells so that the two cell types would maintain distinctive F-I behaviors. However, systematic comparisons of the effect of synaptic input on F-I behavior in fully and partially bistable cells clearly are needed.
; Fleshman et al. 1981; Gardiner 1993; Zengel et al. 1985), which were done in preparations were neuronal activity is suppressed by pentobarbital and thus lacked neuromodulatory input form the brain stem. Although conduction velocity is unlikely to be altered by the exogenous and endogenous neuromodulatory actions in our preparation (see METHODS), conduction velocity ranges for FF and FR cells overlap considerably (e.g., Emonet-Denand et al. 1988). Given these uncertainties, we cannot make a firm conclusion as to the motor unit types in our sample.
). By this estimate, our range of conduction velocities in fully bistable cells was from 80 to 103 mm/s and from 95 to 107 m/s in the partially bistable group. S motor unit conduction velocities range from ~70 to 100 m/s and FR conduction velocities from ~84 to 114 m/s (Zengel et al. 1985). Thus it is quite possible that some of the fully bistable cells in our sample were FR motoneurons. In addition, the relatively high minimum estimated conduction velocity implies the smallest cells were under-represented in our sample. This was likely to occur because of the relatively large electrodes and strict criteria for recording stability that we used.
; Kiehn et al. 1996; Veasey et al. 1995). Indeed, it is quite possible the CNS makes continual adjustments in the activity of these tracts to match the electrical properties of motoneurons to the task at hand (cf. Jacobs and Fornal 1993). Thus motoneurons can be said to have a range of electrical behaviors. At one extreme are the properties measured in deeply anesthetized preparations when activity in the monoaminergic tracts is suppressed. In this study, we sought to quantify motoneuron electrical properties at the other end of the spectrum, the fully "bistable" state when monoamines have near maximal actions.
). Because S units are likely to be heavily used in postural tasks (Walmsley et al. 1978), the data presented here strongly supports the hypothesis (Kiehn et al. 1996) that bistability is an integral part of postural control. Furthermore, our systematic comparisons of F-I relations provide a picture of how fully bistable motoneurons might be advantageous for steady posture and partially bistable motoneurons advantageous for corrections for large postural disturbances.
; Henneman and Mendell 1981)]. Rheobase is the primary determinant of motor unit recruitment order because low rheobase cells require only a small amount of synaptic current to reach threshold. Although rheobase values were lower in our data sample than in previous studies in the pentobarbital-anesthetized preparation, there was still a good correlation between rheobase and conduction velocity. Thus cells with the slowest conduction velocities, which are likely to be type S, will tend to be recruited first (cf. Bawa et al. 1984; Cope and Clark 1991).
; Kernell et al. 1983) (the average self-sustained firing rate of fully bistable cells in our sample was 21 ± 10 Hz).
have shown that electrical stimulation near the mesencephalic locomotor region in the decerebrate cat preparation produces firing patterns much like those described above. That is, S units maintain a steady firing rate, while F units rapidly peak and decline. Kiehn et al. (1996) have found that elimination of monoamines in the spinal cord by neurotoxins virtually eliminates tonic electromyographic patterns in chronic recordings in the rat. Moreover, recent evidence suggests the motor units in humans do exhibit self-sustained firing (Gorassini et al. 1998; Kiehn and Eken 1997). All these data are consistent with the hypothesis that monoaminergic input to motoneurons plays an essential role in postural control. The question of how motoneuron properties are modulated in this and other tasks is clearly essential one for understanding the genesis of movement.
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ACKNOWLEDGEMENTS |
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We thank Dr. Jack F. Miller for assisting in some of these experiments and K. D. Paul for developing our data acquisition and analysis software. We also thank two anonymous referees for recommendations for improving this paper.
This work was supported by National Institute of Neurological Disorders and Stroke Grant NS-34382. R. H. Lee was supported in part by a National Institute of Child Health and Human Development Training Grant (T32-HD-07418).
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FOOTNOTES |
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Address for reprint requests: C. J. Heckman, Dept. of Physiology M211, Northwestern University Medical School, Evanston, IL 60201.
Received 2 February 1998; accepted in final form 4 May 1998.
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Abstract
Introduction
Methods
Results
Discussion
References
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