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The Journal of Neurophysiology Vol. 80 No. 4 October 1998, pp. 2023-2037
Copyright ©1998 by the American Physiological Society
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, Copenhagen N, Denmark
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ABSTRACT |
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 Abstract
 Introduction
Methods
Results
Discussion
References
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Bennett, David J., Hans Hultborn, Brent Fedirchuk, and Monica Gorassini. Synaptic activation of plateaus in hindlimb motoneurons of decerebrate cats. J. Neurophysiol. 80: 2023-2037, 1998. Intracellular recordings were made from hindlimb motoneurons in decerebrate cats to study how synaptic inputs could affect the threshold at which plateau potentials are activated with current injections through the recording microelectrode in the cell body. This study was prompted by recent evidence that the noninactivating inward currents that regeneratively produce the plateau potentials arise (partly) from dendritic conductances, which may be relatively more accessible to synaptic input than to current injected into the soma. Initially, cells were studied by injecting a slow triangular current ramp intracellularly to determine the threshold for activation of the plateau. In cells where the sodium spikes were blocked with intracellular QX314, plateau activation was readily seen as a sudden jump in membrane potential, which was not directly reversed as the current was decreased. With normal spiking, the plateau activation (the noninactivating inward current) was reflected by a steep and sustained jump in firing rate that was not directly reversed as the current was decreased. Importantly, the threshold for plateau activation (at 34 Hz on average) was significantly above the recruitment level (13 Hz on average). When tonic synaptic excitation [excitatory postsynaptic potentials (EPSPs)] was provided either by stretching the triceps surae muscle or by stimulating its nerve at a high frequency, the threshold for plateau activation by intracellular current injection was significantly lowered (by 12 Hz or 5.8 mV on average, without and with QX314, respectively). Conversely, tonic synaptic inhibition [inhibitory postsynaptic potentials (IPSPs)], provided by appropriate nerve stimulation, significantly raised the plateau threshold (by 19 Hz or 7.6 mV on average). These effects were graded with the intensity of tonic EPSPs and IPSPs. Strong enough EPSPs brought the plateau threshold down sufficiently that it was activated by the intracellular current soon after recruitment. A further increase in tonic EPSPs recruited the cell directly, and in this case the plateau was activated at or before recruitment. The finding that synaptic excitation can produce plateau activation below the recruitment level is of importance for the interpretation of its function. With this low-threshold activation, the plateau potentials are likely important in securing an effective recruitment to frequencies that produce significant force generation and would subsequently have no further affect on the frequency modulation, other than to provide a steady depolarizing bias that would help to sustain firing (cf. self-sustained firing). Additional jumps in frequency after recruitment (i.e., bistable firing) would not be expected.
The classical view of the mammalian spinal motoneuron, which emerged from the laboratories of Eccles and Granit in the 1950s and 1960s, held that the cell membrane in areas of synaptic contact (largely the dendrites) was essentially passive, allowing a linear summation of synaptic inputs and passive transmission to the spike-initiating region (i.e., initial segment/soma) (Granit et al. 1966a
Intracellular recordings were made from motoneurons of the left hindlimb of 14 male cats, with approval from the local animal ethics committee. The animals were initially anesthetized with the short-acting drug Saffan (1.5 ml/kg im; Pitman-Moore) in order to place two venous lines in the front legs, a carotid arterial blood pressure line, and a tracheal tube. As the Saffan wore off, the animal was kept under deep anesthetic by inhalation of ether (1-2%) mixed in nitrous oxide (50%) and oxygen (50%). Atropine (0.1 mg/kg sc) and dexamethasone (1 mg/kg iv) were given to prevent congestion and CNS swelling, respectively. Exhaled C02 was monitored and maintained between 4 and 5%, and the animal was ventilated if necessary during the anesthetic. A bicarbonate mixture (1.7% NaHCO3 and 10% glucose in saline) was given continuously through the experiment to counter acidosis, with doses determined in several cats with blood gas analysis. The bladder was catheterized. A rectal probe and heating lamp and pad were used to maintain the cat's temperature between 36 and 37°C during surgery. Additional temperature probes were placed in the spinal and leg pools during recordings (see below), and warm air was also blown under the cat. During surgery, fluid (saline or Dextran) was sometimes given to maintain the pressure above 80 mmHg. When the blood pressure fell after surgery (often ~5-8 h later) the noradrenergic (NA) agonist Effortil (Boehringer) or NA were given intravenously to effect, with a slow perfusion pump.
Decerebration, nerve preparation, and laminectomy
Cats were anemically decerebrated by ligating the basilar and both common carotid arteries, a procedure that has been shown to produce a decerebration that involves all cortical tissue above the pons, where the basilar ligature is placed (Crone et al. 1988 Nerve stimulation, intracellular electrodes, and recording
Nerves were stimulated with pairs of silver wire electrodes to antidromically activate and identify motoneurons. A monopolar silver wire electrode was placed over the cord dorsum for recording the incoming nerve volley. Intracellular recordings were made with conventional glass electrodes, with tips broken to 1.2-1.5 µm, and pressure filled with 3 M potassium acetate to give a 5- to 8-M Plateau identification
A slowly increasing and then decreasing current ramp ("triangular" pulses, ~5 nA/s) was injected to test for the presence of plateaus (Fig. 1B) (see also Hounsgaard et al. 1988
"Secondary" slope in F-I relation
We have used the terminology primary and secondary slope to denote the shallow and then steep F-I slopes that occur during the slow current ramps. These slopes do not necessarily correspond to the classical primary and secondary ranges. Classical experiments to compute F-I slopes involve responses to current steps, computed at different times after the step, including when steady-state firing is reached (Granit et al. 1966a Drugs to promote plateaus
The anemic decerebrate cats without pharmacological treatment can exhibit plateaus during intracellular current injection, with an associated rigidity mediated by the Intracellular plateau activation with current ramps
Intracellular recordings were made from 91 hindlimb motoneurons in 14 decerebrate cats, and plateaus were identified as detailed in METHODS (see section, Plateau identification). Initially, current was injected through the recording microelectrode with a ramp profile to determine the threshold for plateau activation under resting conditions, without muscle stretch. A plateau was assumed to be initiated if there was a sustained jump in firing rate that was not immediately reversed as the injected current was reduced (see counterclockwise hysteresis and self-sustained firing in Figs. 1B and 2). The term "plateau" is somewhat misleading, because during the plateau the firing rate and potential were not clamped at a particular level and could readily be increased or decreased by the current ramp (Figs. 1B and 2). In this case it might be more appropriate to refer to the activation of noninactivating inward currents that caused the sustained increase in firing, but, because we did not measure these currents directly, we retain the terminology "plateau," with the implication that the noninactivating inward currents were activated (Hultborn and Kiehn 1992
Influence of tonic synaptic excitation [excitatory postsynaptic potentials (EPSPs) below recruitment level] on plateaus
Our main finding was that the plateau threshold, measured during intracellular current injection as above, was substantially lowered by peripheral excitatory synaptic input (EPSPs, Fig. 2, A and B). The majority of the cells recorded were GS motoneurons, and we produced the EPSPs with tonic stretch of the GS muscle. If stable penetrations were made from other identifiable cells, we produced tonic EPSPs by high-frequency stimulation of heteronymous nerves. In all cases, EPSPs were adjusted to be subthreshold for firing (muscle length usually 10-12 mm from slack, but less in units that fired at this length; nerve stimulation 1-2T). With such subthreshold EPSPs, intracellular current ramps initiated plateaus at significantly lower frequencies of firing (see arrows in Fig. 2B; mean drop
Influence of tonic synaptic inhibition [inhibitory postsynaptic potentials (IPSPs)] on plateaus
Because tonic EPSPs facilitated plateaus, we investigated whether the opposite effect might be achieved by tonic inhibitory synaptic input, IPSPs (by high-frequency nerve stimulation; e.g., CP nerve, 100 Hz, 2T; Fig. 2). Indeed, such IPSPs significantly increased the threshold frequency for plateau activation (Fig. 2, right; P < 0.05, Table 1, 100% of cells tested affected, although 9 cells were not tested because IPSPs could not be produced). In cells that did not exhibit plateaus, but exhibited a secondary slope, tonic IPSPs significantly increased the transition frequency (P < 0.05, Table 1).
Influence of tonic synaptic excitation that recruits cell directly
When the synaptic excitation was increased to bring a cell just below the firing level, the threshold for activating the plateau with intracellular current was lowered to the point where the plateau was activated soon after the intracellular current ramp started, as mentioned above (e.g., Fig. 2, left). We thus hypothesized that further activation might lower the plateau threshold below the firing level. Indeed, we found that when the synaptic excitation (muscle stretch) was slightly suprathreshold for firing (i.e., increased to recruit the cell at a low firing rate), then subsequent current injected into the cell could not produce a jump in frequency or hysteresis (middle plot of Fig. 3A; lack of hysteresis not shown, because the firing on the downward current ramp obscures that on the upward ramp), even though it could without the stretch (right plot in Fig. 3A). In this case there was either 1) no plateau, or 2) a plateau was already initiated by the synaptic input and the injected current could not activate a further plateau. We favor the latter interpretation, because another current ramp that was applied starting from a hyperpolarized level, to stop the initial firing produced by the muscle stretch, caused hysteresis indicative of plateau activation (left plot in Fig. 3A). In this case the plateau was activated as soon as firing began, as seen by the steep slope at this time. The AHP amplitude was also reduced when firing was initiated by stretch (Fig. 3A, middle, and Fig. 3B2), as compared with when firing occurred without a plateau (Fig. 3A, right, and Fig. 3B1). As we describe below, the reduction in AHP size was characteristic of a plateau activation.
Intracellular plateau activation when Na+ spikes were inactivated with QX314
From the above experiments, we suspected that during synaptic activation, the threshold for the activation of the plateau decreased close to the recruitment level of the cell. However, because the large rhythmic changes in membrane potential at the initiation of firing obscured subtle changes in the membrane potential during plateau activation (Figs. 1 and 2), we studied 17 cells with firing inactivated with intracellular QX314. Because plateaus are not thought to be carried by sodium channels in motoneurons, we were able to study the effects of synaptic input on the plateau activation threshold as described above, but analyzing potential rather than frequency. As before, a current ramp was injected into the cell, and a plateau was assumed to be activated at a particular threshold if a steep rise in potential occurred that was not directly reversed during lowering of the current (Fig. 4). With QX314 the plateau activation occurred in all cells tested and was particularly easy to spot, because it usually occurred rapidly with an overshoot in membrane potential (85% of cells, example marked with an asterisk in Fig. 4B). The overshoot lasted ~80 ms and may have been a broad, partially blocked sodium spike, or perhaps a calcium overshoot (spike) associated with the plateau activation (Hounsgaard and Kiehn 1993
Stretch activated plateaus with QX314
To further quantify the activation of plateaus during synaptic input, we studied their activation during phasic (sinusoidal) stretching, while holding the cells at different levels of hyperpolarization with intracellular current injection. We present results from cells with QX314 first (Fig. 6), because the interpretation is simpler. In some cells we were able to obtain a measure of the firing level at recruitment immediately upon penetration, before the QX314 took effect (horizontal line in Fig. 6A), and so we had an approximate idea of the degree to which the plateau activation was below the firing level.
Stretch activated plateaus without QX314
We repeated these stretch reflex experiments in 18 cells without QX314 (with sinusoidal and/or triangular stretching, the latter not shown), so that the plateau thresholds could be directly compared with the firing level (only cells that exhibited plateaus with ramp intracellular current injections were studied). A typical cell is shown in Fig. 7A using the same format as in Fig. 6B. As before, at hyperpolarized levels the stretch reflex response simply reflected the synaptic input (Ia afferents). As the bias current was removed, we saw voltage-dependent amplification and prolongation of the stretch reflex responses (by 3-8 mV in 89% of cells tested), indicative of plateau activation, and this plateau activation was often significantly below the firing level (Fig. 7). Indications of plateau activation at or below the recruitment level occurred in 86% of cells (12/14; 4 cells needed current bias to fire and were not included).
Self-sustained firing
The plateau activation during muscle stretch could often be seen from the firing rate profiles. For example, for the cell in Fig. 8 without a current bias (0-nA condition), the first stretch caused firing that was sustained during shortening, even though the effective synaptic activation, predicted from the hyperpolarized stretch response, only occurred during stretch (bottom of Fig. 8, Synaptic activation of plateaus in high-threshold "fast" motoneurons
In higher threshold cells the muscle stretch could not, by itself, recruit the cell or activate the plateau. However, when these cells were depolarized with a steady current bias, the plateau could be activated by a subsequent stretch. For example, in the cell shown in Fig. 9, with a bias current of 10 nA the stretch reflex produced phasic depolarizations just below the plateau threshold (1st 3 stretches, cell with QX314). When the current was increased to 11 nA, the subsequent stretch activated the plateau. However, in these fast motoneurons that required large injected currents to aid in plateau activation, the plateau was sustainable for only short periods of time (<5 s), consistent with similar findings in the turtle (Russo 1994
AHP changes with plateaus and synaptic input
As a final topic, we investigated the changes in the interspike membrane trajectories (AHP shape) during plateaus and compared them with and without muscle stretch. When a plateau was activated by intracellular current injection, the AHP amplitude was significantly reduced compared with before the plateau activation, even when comparisons were made at equal interspike intervals, as shown in Fig. 3B2 (see also Brownstone et al. 1992 The results in this study demonstrate that a tonic background synaptic excitation dramatically reduces the threshold for plateau activation by intracellular current injection. This refers to the threshold seen from the soma, either by recording the membrane potential at which the plateau potential was initiated, or the firing frequency at which the steep slope (the frequency "jump") began. When the synaptic excitation was strong enough to recruit the cell, the plateau threshold was brought down to, or below, the recruitment level. That implies, as demonstrated experimentally, that when synaptic excitation alone (no current injection) recruited the motoneuron, the plateau was already initiated below, or at, the recruitment level. The latter results, which may be of great functional significance, are based on recordings from low-threshold, early recruited motoneurons. It was also demonstrated that synaptic inhibition had the opposite effect on the threshold of plateau activation. Although this is an important finding (see below), it may be of little functional significance because the motoneurons obviously will never be recruited during a dominating inhibition unless depolarizing current is injected as part of an experimental protocol.
Interpretations based on dendritic model
As suggested in the INTRODUCTION, this dendritic model assumes that on average both the plateaus and the synaptic input exert a major part of their effects through electrotonically distant dendrites, because they arise at least partly from the dendrites, and the surface area of the dendrites is very large in comparison to the soma (20-30 times larger) (Cullheim et al. 1987 Alternative explanations
We do not know whether the amount of dendritic depolarization to activate the plateau remains unchanged with synaptic excitation, as we assumed above. Actually, the recent results from turtle neurons by Russo and Hounsgaard (1994, 1996) and Svirskis and Hounsgaard (1995 Possible relations between "secondary range" firing and the plateau current
Inward currents do not normally produce maintained plateaus or F-I relations with counterclockwise hysteresis (with triangular current injections) in spinal and/or anesthetized animals. That is, a regenerative response requires a reduction of the outward currents (see INTRODUCTION). Nevertheless, these noninactivating inward currents may be important for the high-frequency firing in response to sustained current injections in what has classically been called the secondary range in the F-I relation. In particular, Schwindt and Crill (1982) Functional implications
We suggest that our results lead to a simpler, rather than more complex, picture of mammalian motoneuron behavior. The plateaus are often activated during recruitment, and a short time after recruitment further plateau activation is impossible (i.e., bistable firing not likely in this case). Thus, during tonic firing, the plateaus have no influence other than to add a steady depolarizing current. For example, once above the firing threshold the plateaus no longer influence the stretch reflex responses recorded in motoneurons (compare
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
). It is now known that several active membrane properties further shape the motoneuronal output, including voltage-dependent, noninactivating inward currents (likely Ca2+-mediated) (Schwindt and Crill 1980a-c, 1982, 1984). In particular, these inward currents can regeneratively produce prolonged depolarizations (plateau potentials) and associated self-sustained firing when facilitated by brain stem serotonergic and noradrenergic pathways or for that matter, any intervention that sufficiently reduces opposing outward currents (e.g., K+) (see reviews, Hultborn and Kiehn 1992; Schwindt and Crill 1984). If these active membrane properties function at or near the soma, they would simply serve to amplify the motoneuron output, so that Granit's concept of linear summation of synaptic input on the dendrites may still hold qualitatively. However, recent evidence from turtle motoneurons has indicated that these noninactivating inward currents arise from channels that cover the dendritic tree (Hounsgaard and Kiehn 1993), thus raising the possibility that inputs to motoneurons may be differentially amplified by these currents, depending on their distance from the soma. We have investigated this possibility because previous results, which we describe below, have suggested a discrepancy between the threshold for activation of plateau potentials by synaptic input, compared with current injected directly into the soma through a microelectrode.
; Heckman and Lee 1996; Hounsgaard et al. 1988). With such intracellular activation the plateau threshold is above the recruitment level of the cell, so moderate to high levels of firing are reached before the plateau is activated, and the plateau activation produces a distinct jump to a still higher firing rate (i.e., bistable firing) (Eken et al. 1989; see Figs. 1d and 5 in Hounsgaard et al. 1988). In an effort to determine whether plateau potentials occur in awake freely moving animals and humans, Eken and Kiehn (1989, 1992) recorded single motor units and looked for such sustained jumps in firing (bistable firing) in response to short-lasting excitatory synaptic inputs. However, these studies and the more recent studies of Gorassini et al. (1998a,b; see also Eken and Kiehn 1997) have found that bistable firing is uncommon, and instead more often the short-lasting synaptic excitation caused a recruitment of new motor units, which continued to fire after the synaptic excitation was removed (self-sustained firing). In retrospect, these findings are consistent with the original cat studies, where short-lasting synaptic excitation triggered plateau potentials that caused intracellularly recorded motoneurons (Hounsgaard et al. 1988) to also jump from rest to sustained firing (self-sustained firing) (e.g., cat motor units in Crone et al. 1988; and Fig. 1b of Hounsgaard et al. 1988). Apparently, in this situation where the plateau is activated by synaptic input alone, the threshold for activation appears to be at or below the recruitment level, and thus much lower than when activated by intracellular current as described above. The difference between the threshold for intracellular and synaptic activation of plateaus was not specifically addressed in the original cat studies, but now that it appears to be important in understanding plateaus in awake animals and humans, we have reinvestigated this issue.
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FIG. 1.
Schematic of experiment and possible model of plateau activation in motoneurons (see DISCUSSION). A: plateau activation by intracellular current injection was studied with and without a steady (tonic) peripheral synaptic input (Ia afferent excitation, and reciprocal Ia inhibition). B: method of measuring plateau threshold, shown for a gastrocnemius-soleus (GS) motoneuron. A linearly increasing current (ramp) was injected into the cell, while measuring the membrane potential and instantaneous firing frequency. The plateau was considered to be initiated at the point where the frequency and potential jumped steeply (plateau threshold), and a subsequent decrease in current did not reverse this steep jump. In this case the plateau threshold was 27 Hz and remained activated after the cell stopped firing, until the point marked with an arrow. The changes in membrane potential can be seen more clearly during firing from the superimposed thin line, which is the potential after filtering out the high-frequency spikes (low-pass filter of 5 Hz). Tops of spikes clipped in this and subsequent plots. C: frequency plotted against current for data shown in Fig. 1B. Arrows show direction of time. Note hysteresis and self-sustained firing (firing below current at recruitment), indicative of a plateau.
) have shown that these inward currents arise both in the dendrites and soma, and thus considering the large size of the dendritic tree compared with the soma (e.g., 20-30 times the area of the soma) (Cullheim et al. 1987), both these inward currents and the synaptic input should indeed act primarily on the dendrites. Thus synaptic input should activate the plateau potentials relatively easily, whereas current injected into the soma through a microelectrode should easily activate the sodium spikes in the initial segment/soma, but less effectively activate the inward currents in the dendrites (depicted in Fig. 1A). Although this possible differential activation of synaptic and somatic inputs on the plateaus depends critically on there being sufficient electrotonic attenuation between the soma and dendrites, it does not require that the synaptic input and plateaus have to arise in the extreme distal dendrites. Even relatively modest distances from the soma (e.g., half a space constant), consistent with the known average location of Ia afferent inputs, should suffice (see DISCUSSION) (Brown and Fyffe 1981; Redman and Walmsley 1983; Segev et al. 1990).
).
METHODS
Abstract
Introduction
Methods
Results
Discussion
References
). The anesthetic was removed 5-6 h after ligating the vessels, and the decerebration was verified to be clinically complete in all animals by the development of tonic extensor muscle tone (alpha rigidity) (Crone et al. 1988), lack of spontaneous movements, and large nonreactive pupils.
1 h. A pneumothorax was performed after the pancuronium injection, and artificial respiration was initiated as soon as the drug took effect. Skin flaps were used to make mineral oil pools over the spinal cord and leg. The Achilles tendon was tied to a muscle puller (310B, Cambridge), and the portion that was out of the leg pool was kept moist with mineral oil-soaked cotton.
resistance. Some electrodes also had the sodium channel blocker QX314 mixed with the potassium acetate to inactivate spiking (100-mM solution used to fill tip of electrode, potassium acetate used to complete filling of electrode; RBI) (Brownstone et al. 1994). Recordings were made with an Axoclamp2B amplifier (Axon Instruments) in either standard bridge mode, or in discontinuous current clamp mode (DCC; 2- and 5-kHz sampling rate, followed by 1-kHz low-pass filter) (cf. Brownstone et al. 1994). The DCC mode allowed for more accurate measurements of membrane potential despite changes in electrode resistance with injected current and was used during experiments with QX314.
3-nA pulse, rheobase, conduction velocity, afterhyperpolarization (AHP) duration and amplitude. Cells with resting membrane potentials more negative than 55 mV and spike height of >65 mV were included in the results.
). The membrane potential increased roughly linearly with the current until firing began, at which point the mean potential transiently dropped due to AHP initiation (see thin line in Fig. 1B). The firing rate (and membrane potential) then increased linearly with the current (primary slope, marked p) until a critical transition frequency was reached, above which the frequency (and potential) increased steeply (secondary slope marked s in Fig. 1B; see note on terminology below). This steep rise, or jump, in frequency usually indicated the initiation of the plateau (or rather the associated noninactivating inward currents), because bringing down the injected current after this jump did not bring the firing rate back to that before the jump at matched current levels. This can be most clearly seen by plotting current against frequency and observing the frequency differences at a given current level (Fig. 1C; cf. counterclockwise hysteresis loop) (Hounsgaard et al. 1988). Also in Figs. 1B and 2 we have drawn, for reference, the firing rate profile that would be predicted if the plateau (inward currents) had not been initiated (thin lines; extrapolated from the primary slopes). The threshold at which the plateau was initiated (i.e., the frequency at which a steep jump in firing rate began; i.e., plateau threshold) was the main subject of investigation, and is marked with an arrow in Fig. 1B. This plateau threshold and the amplitude of the frequency jump were examined during ramp current injections at different levels of synaptic input produced by either muscle stretch or high-frequency nerve stimulation. Both steady and sinusoidally modulated muscle stretch was used.
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FIG. 2.
Influence of tonic synaptic input on plateau in GS motoneuron. A, middle plot: control/resting situation similar to that of Fig. 1C. Left plot: effect of tonic muscle stretch [excitatory postsynaptic potentials (EPSPs), 10 mm] applied throughout the current ramp shown. This tonic EPSP was adjusted to be below the recruitment level (subthreshold) before the current ramp. Right plot: affect of tonic inhibitory nerve stimulation [inhibitory postsynaptic potentials (IPSPs) from ipsi- and contralateral common peroneal (CP) stim. 2T, 100 Hz]. Hashed regions show contributions of plateau in each case. B: composite of results from A, showing responses during ascending phase of ramp plotted against current. Note that the plateau threshold frequency (arrows) is lowered by EPSPs and raised by IPSPs.
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FIG. 10.
Influence of plateau on AHP shape. Responses of 2 low-threshold GS motoneurons to ramp current injections. Same format as Fig. 1B. A: cell with plateau activated a few spikes after recruitment (arrow), as seen from increase in firing rate, which was sustained for currents substantially negative to the recruitment current (cf. self-sustained firing). Membrane trajectory before and after the plateau was activated are shown on an expanded time scale, for 2 points with equal interspike intervals. Note the reduced AHP amplitude and the appearance of an afterdepolarization labeled with arrows. B: cell with plateau activated during recruitment, because there was no jump in firing rate and yet a marked asymmetry in the firing profile (cf. self-sustained firing). Note the 2 closely spaced spikes at recruitment (doublet). Also, note appearance of the AHP afterdepolarization during firing, compared with during antidromic stimulation (bottom right, c).
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FIG. 4.
Influence of synaptic input on plateau activation after spike inactivation. GS motoneuron recorded with QX314. A and B: same format as Fig. 2. Recordings taken in DCC mode, compensated for electrode rectification as calibrated extracellularly. Note that the plateau threshold was again lowered and raised, respectively, by tonic EPSPs (stretch) and IPSPs (CP stimulation; see arrows). Two results shown for CP stimulation, the one on the right was with a stronger stimulation that eliminated the plateau. Also, note the rapid plateau activation in each case, with a characteristic overshoot in membrane potential (marked with asterisk in resting condition). C: potential plotted against current [voltage-current (V-I) plot] for the same data, showing hysteresis as in Fig. 1C, time indicated by diagonal arrows for one plot. Line thickness varied to distinguish plots.
,b). Our F-I slopes most closely correspond to these steady-state responses, because the ramps were slow. This issue is taken up further in the DISCUSSION.
), we tested how the threshold for the onset of the secondary slope (transition frequency) also changed with synaptic input. Basically, this was a repeat of Granit's classical experiments (Granit et al. 1966a,b), except that a ramp, rather than a series of step inputs, were used.
-motoneurons (Hounsgaard et al. 1988). This situation relies on the integrity of the brain stem and its descending monoaminergic pathways, including actions of serotonin (5-HT) and norepinephrine (Conway et al. 1988; Hounsgaard et al. 1988). However, some cats did not exhibit plateau behavior and had poor muscle tone. In these cats we gave small doses of the 5-HT precursor 5-hydroxytryptophan (5-HTP; 5-10 mg/kg) to facilitate plateaus. These doses were below those necessary to initiate plateaus in spinal cats (>50 mg/kg), indicating that brain stem monoaminergic tracts still had considerable influence on the spinal cord (Hounsgaard et al. 1988). In two cats, we facilitated plateaus with the monoamine oxidase inhibitor Nialamide (50 mg/kg) (Conway et al. 1988), rather than 5-HTP, which presumably facilitated the actions of endogenous monoamines, including 5-HT. We consider it unlikely that these drug interventions affected our conclusions, because our main objective was to study the interaction of synaptic input with plateaus and not the occurrence of plateaus per se.
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
; Schwindt and Crill 1980a-c, 1982).
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TABLE 1.
Summary of effects of tonic synaptic excitation (EPSP, below recruitment level) and inhibition (IPSP) on motoneurons with and without plateaus
and Svirskis and Hounsgaard (1995, 1997), and for the present material in a companion paper (Bennett et al. 1998). For the results described below, we have avoided it by waiting >20 s between trials (or repeatedly activating a plateau under the same conditions until a steady state was reached).
12 Hz, P < 0.05, Table 1, 87% cells affected). The plateau amplitude (size of the frequency jump during plateau activation, Table 1) was not altered, but it was often activated more slowly (cf. shallower secondary slope; Fig. 2A). Of course, the EPSPs also lowered the amount of current needed to initiate the plateau, but this was expected, even with simple linear summation (Granit et al. 1966a). With EPSPs, the plateau threshold was often lowered to near the initial recruitment rate (Fig. 2A, left), and on average to within 8.5 Hz of this rate (Table 1).
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FIG. 3.
Influence of suprathreshold synaptic input on plateau. A: responses to ramp current injection, as in Fig. 2, but for low-threshold GS motoneuron that could be recruited directly by tonic muscle stretch. Right plot: frequency-current (F-I) relation showing jump to plateau (horizontal arrow) and hysteresis under control/resting conditions. Diagonal arrows show direction of time. Middle plot: synaptic input produced firing just at recruitment rate (suprathreshold; rectangular box, at 0 nA current), which was followed immediately by a current ramp to test for plateau activation. Note that there was no jump in firing rate in this case (see text). Left plot: same as previous, but a hyperpolarizing current bias was applied after the cell was recruited by muscle stretch, to terminate the firing produced by the muscle stretch. A current ramp starting from this hyperpolarized level caused an early jump in frequency, and hysteresis indicative of a plateau. B: membrane potentials showing AHP size and shape before (1), and after plateau activation with either intracellular current (2) or muscle stretch (3). Stars indicate interspike intervals of comparable durations, and arrows show appearance of afterdepolarization. Data corresponds to points labeled 1-3 in A.
; see DISCUSSION).
). Thus the effect of IPSPs was to bring the threshold for the secondary slope and/or plateau closer to this maximum (Fig. 2, right). Strong enough IPSPs could raise this threshold to meet the maximum rate, so the secondary slope and jump to the plateau was reduced or eliminated (Fig. 2A, see also Fig. 4).
).
60 mV (Fig. 4; 56.4 mV on average, Table 1), which was likely below the sodium threshold, if firing were not blocked with QX314. The effects of IPSPs were also graded. Strong enough IPSPs eliminated the jump to the plateau, because there was a maximum depolarization above which it was difficult to depolarize the cell further (e.g., 48 mV in Fig. 4B), just as with the rate limiting seen without QX314.
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FIG. 5.
Gradation of plateau threshold with different levels of muscle stretch. GS motoneuron recorded with QX314, in DCC mode. Same format as Fig. 4B. Right-most plot is resting condition with no prestretch. Muscle length increased to 12 cm in equal steps for plots to left of the resting condition plot. Plateau thresholds shown with arrows, and decreased with increasing length.
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FIG. 6.
Stretch activated plateaus with QX314. A: recording from GS motoneuron with QX314 to inactivate spiking, during sinusoidal stretching of GS muscle. At the left, the cell was hyperpolarized by 5 nA, and there was only a reflex response during the stretch phase of the sinusoid (upward slope). When the hyperpolarizing bias was removed, a plateau was activated phasically with each stretch, until the bias was reduced to 1 nA, after which the stretch produced a tonic activation of the plateau. B: averaged and smoothed stretch responses at the different bias currents, for the same cell as in A. The most hyperpolarized condition showed no plateau, but at more depolarized levels there was a plateau that started at the thresholds marked with arrows, and increased in amplitude and duration as the bias was reduced. The plateau activation traversed the estimated firing level (horizontal line). C: on the left the plateau was activated twice by stretch and terminated by a strong inhibitory stimulation (CP nerve stimulation train, 100 Hz, 10T, 500 ms, at asterisks). The same CP stimulation had no long-lasting effect when there was no plateau (right). D: input/output properties of the cell. Reflex responses from B plotted against the reflex response at the most hyperpolarized level (9 nA); the latter was assumed to represent the synaptic input, without influence of the plateaus. Direction of time shown with arrows as in Fig. 4C. Data in C smoothed with 5-Hz low-pass filter.
5 to 2 nA conditions in Fig. 6A; see also Fig. 6B). When the holding current was further reduced, the next stretch cycle activated the plateau tonically (Fig. 6A, right). The final plateau level was above the estimated firing level (horizontal line). Subsequent stretch responses where superimposed on this tonic plateau.
5 to 2 nA. Also, note that the plateau activation started below the predicted initial firing level (horizontal line) and continued until it was fully activated above this level. Thus, for example in the 2 nA condition, had the firing not been inactivated, the stretch would have recruited the cell phasically, and the cell would have continued to fire during muscle shortening, because of the plateau activation. Once the plateau was fully activated, the responses to stretch were smaller, and comparable with those at hyperpolarized levels (9 nA condition), consistent with the interpretation that the inward currents responsible for the plateau were tonically activated and not able to further contribute to the stretch reflex.
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FIG. 7.
Stretch activated plateaus without QX314. A and B: response of soleus motoneuron to sinusoidal muscle stretch with different current bias. Same format as Fig. 6, A and B. Note the amplification and prolongation of the stretch reflex as the hyperpolarizing bias was reduced (cf. plateau activation). The plateau was tonically activated in the 0-nA condition; thus the responses were smaller as was seen in Fig. 6. Firing occurred in this 0-nA condition, so it is shown displaced vertically for clarity.
9 nA bias current, shown in Fig. 6B, but not A), then we can compare this synaptic input with responses at other bias currents, to infer the influence of the plateau on the cell's input/output properties. In other words, if we plot the membrane potential at a given current bias against that at the 9-nA bias (as in Fig. 6D), then we can examine the degree of hysteresis produced by the plateau, as was done with the V-I plots in Fig. 4C. In this format the magnitude of the amplification of the stretch reflex response produced by the plateau is reflected in the openness of the hysteresis loop plots. As seen in Fig. 6D, hysteresis occurred over a range of hyperpolarizing bias currents, where the plateau was phasically activated with each stretch. Further, once a plateau was tonically active (1 nA condition in Fig. 6D), the cell responded without hysteresis or amplification of the stretch reflex response, as mentioned above. In all QX314-treated cells tested with phasic stretching (n = 5), we found similar subthreshold voltage-dependent plateau activation (arrows in Fig. 6B).
; Russo and Hounsgaard 1994, 1996); that is, activation of the plateau become progressively larger with each stretch cycle, unlike in Fig. 6. In these cells we waited for a steady state to be reached during the sinusoidal stretch (in a few cycles), before we analyzed the responses.
1-nA bias the first stretch cycle produced a sustained depolarization (Fig. 7A, bottom plot) that was maintained for later stretch cycles (top plot labeled 1 nA), which caused further sustained depolarizations (labeled plateau) and firing.
9-nA response (Fig. 7B; spikes not shown, and data smoothed to see slight hysteresis at the most hyperpolarized level, e.g., 2 nA). The hysteresis response at the 0-nA condition could not be shown because the cell fired throughout most of the stretch. In other cells the plateau threshold was closer to the firing level than in Fig. 7, and recruitment simultaneous with plateau activation made such hysteresis plots impossible to make (e.g., cell in Fig. 8), and analysis of firing rate was necessary.
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FIG. 8.
Transition to plateau and self-sustained firing produced by muscle stretch. Firing rate profiles of GS motoneuron during sinusoidal stretching [rheobase 4 nA, afterhyperpolarization (AHP) half-amplitude duration 62 ms]. Responses shown during the 1st 2 cycles of stretch after the current bias was changed to the levels indicated. The membrane potential with a 9-nA hyperpolarizing bias shown for one stretch cycle, to give an indication of the time course of the actual synaptic excitation produced by the stretch. Note that, although the synaptic excitation only occurred during stretch, firing was maintained during shortening (after the dotted lines in 0- and 1-nA condition; cf. self-sustained firing), suggesting a plateau activation.
9 nA). Such self-sustained firing was even more pronounced when the stretch occurred after a 1-nA bias was introduced, and probably resulted from a plateau activation.
9-nA response). Likely the plateau was activated on the first stretch, causing the steep recruitment step, and then remained activated through to the end of the second stretch cycle. Likewise in the 1-nA condition in Fig. 8, the plateau appeared to be activated by the first stretch, and continued to be activated (tonically) for subsequent stretch cycles. When the cell was activated phasically in the 1-nA condition, there was also a steep increase in rate at recruitment, possibly due to a plateau; however, there was no sustained firing (as in Fig. 7A), because the synaptic input decreased too rapidly for this hyperpolarized level (again see 9-nA response in Fig. 8, which reflected the synaptic input). It should be noted that the self-sustained firing seen in Fig. 8 could be predicted from the data with QX314 in Fig. 6. It is also noteworthy that the cell in Fig. 8 could not produce bistable firing. That is, it was on the plateau even when firing at only a few impulses per second (middle of 0-nA condition). Increases in rate, once the cell was recruited, only occurred gradually as described above.
). That is, the plateau was only maintained for one stretch cycle (~5 s). Subsequent stretch cycles could reactivate the plateau phasically (Fig. 9, right), but to a lesser degree.
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FIG. 9.
Stretch activated plateaus in a high-threshold "fast" motoneuron. Recording from GS motoneuron during muscle stretch and a current bias. Cell recorded with QX314, but rheobase at penetration was 9 nA and AHP half-amplitude duration 24 ms. When the bias current was 11 nA, the stretch elicited phasic plateaus, the first of which lasted for 2 stretch cycles, and started at the arrow indicated. Note that the plateau started sharply with an overshoot as for current injection in Fig. 4, but then tapered off after a few seconds.
). Also, during the plateau there was at times an associated afterdepolarization that made the AHP shape less concave (see arrow in Fig. 3B; cf. delayed depolarization) (Granit et al. 1963), especially in low-threshold "slow" units [84% of low-threshold units with plateaus (21/25) and 25% of higher threshold units (6/24)]. However, note that even though AHP shape changes do occur with plateau activation, they do not necessarily (by themselves) imply that a plateau is present. For example, afterdepolarizations can occur in anesthetized cats where plateaus are not present (Nelson and Burke 1967).
).
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
; also see Segev et al. 1990 in relation to excitation from Ia afferents). Because of this electrotonic attenuation, the dendrites may act in relative isolation and may be more readily depolarized by synaptic input (EPSPs) than by current injected into the soma through an intracellular microelectrode. For example, EPSPs that depolarize the dendrites just subthreshold for plateau activation (on the dendrites) will depolarize the soma less than the dendrites [i.e., EPSP effect attenuated by e
(x/
); that is: Vsepsp = Vd e(x/), where Vsepsp and Vd are the changes in soma and dendritic potentials relative to rest, x is the distance to the soma, and 
is the effective space constant for the dendritic tree]. In this case, a slight increase in excitation or a small amount of current injected into the soma through a microelectrode will activate the plateau on the dendrites. On the contrary, without EPSPs, current injected into the soma to bring the dendritic plateaus to threshold will depolarize the soma (Vs) more than the dendrites, again due to electrotonic attenuation [Vd = Vs e(x/)]. If we assume that the presence of EPSPs does not change the absolute plateau threshold at dendritic level (Vd; see next section), then the soma will be less depolarized when the plateau is activated with the help of EPSPs, than without, as we have observed. Specifically, the plateau threshold seen at the soma and measured relative to rest (65 mV or recruitment rate of 13 Hz) would be lowered by EPSPs by the combined electrotonic attenuation in the two situations described above, as seen by the following substitution
Thus, if the synaptic activation occurred primarily at half a space constant from the soma (x = 0.5
![<IT>Vs</IT><SUB>epsp</SUB><IT> = Vd e</IT><SUP>−(<IT>x</IT>/λ)</SUP> = [<IT>Vs e</IT><SUP>−(<IT>x</IT>/λ)</SUP>]<IT>e</IT><SUP>−(<IT>x</IT>/λ)</SUP> = <IT>Vs e</IT><SUP>−(2<IT>x</IT>/λ)</SUP>](/content/vol80/issue4/fulltext/2023/img001.gif)
; see INTRODUCTION) (and see Segev et al. 1990), then the plateau threshold would be approximately halved by these EPSPs (lowered by a factor of 1/e = 0.4), which is remarkably consistent with our data (Figs. 2 and 4, and Table 1, where on average the plateau threshold was lowered by factors of 0.59 for QX314 data and 0.41 for data during firing). The above computation compares two extreme situations of plateau activation with either intracellular or synaptic input. When plateaus are activated by a combination of synaptic and intracellular current, the plateau threshold will vary in proportion to the synaptic excitation, as is shown with the analysis in the APPENDIX .
as just described. Although this is consistent with the known location of Ia afferent input (Segev 1990; on average 600 µm from soma Brown and Fyffe 1981), there is much less known about the location of inward currents responsible for the plateau. Schwindt and Crill (1980b,c) argued that these currents are within a few hundred micrometers of the soma, based on their ability to voltage clamp them. In contrast, if these inward currents are calcium currents, then the recent results of Talbot and Sayer (1996) would suggest that a substantial portion of this current is generated distally. That is, these authors found that, in addition to its effect on sodium channels, intracellular QX314 reduced both low- and high-threshold calcium currents in hippocampal neurons. Thus the presence of plateaus following QX314 in our experiments might then imply that the inward currents are significantly more distal than the sodium channels responsible for the action potential (i.e., distal enough to be not influenced by QX314). Finally, the location of the synapses of the Ia inhibitory interneurons that produce the IPSPs on the motoneurons is likewise rather uncertain, although the results of Burke et al. (1971) would suggest that they may be more proximal than synapses from Renshaw cells, which are themselves close to the soma (at 0.25) (Fyffe 1991).
, Fig. 1). That is, a motoneuron was, on one hand, shown to be brought from rest to sustained firing at a relatively low rate by a brief nerve stimulation, due to a plateau activation (<14 Hz; self-sustained firing). On the other hand, when a depolarizing bias current was applied to the same cell, it fired at a higher rate (14 Hz) without the plateau activated, because the same brief nerve stimulation caused a sustained jump to a still higher firing rate (24 Hz), due to the plateau activation. The latter situation is bistable firing (see INTRODUCTION), and in retrospect, it may now be explained by the intracellular current bias raising the plateau threshold.
, 1997), on a voltage-dependent facilitation (reduction of threshold; warm-up) of plateau generating currents, would indicate that the local thresholds of the plateau potentials could be decreased by a tonic (synaptic) depolarization. It is, however, unclear whether the tonic EPSPs in the present study (Figs. 2 and 4) would produce such warm-up, because they did not themselves activate the plateau, and warm-up has only been shown to occur above or "just subthreshold" to the plateau (see Bennett et al. 1998 for further discussion; Russo and Hounsgaard 1996).
). However, they would not change the dendritic interpretation discussed above. That is, the Ia EPSPs seem to be mainly mediated by non-NMDA receptors (e.g., Engberg et al. 1993), so NMDA channels would not be directly activated by the tonic EPSPs during muscle stretch. It is possible that other ongoing synaptic input (not related to the muscle stretch; cf. decerebrate preparation) could activate NMDA receptors, and these would certainly participate in generation of the plateau potential. However, the action of these NMDA receptors would be very much like that of the other intrinsic inward (plateau) currents already discussed; both would be more readily activated by other synaptic inputs (from muscle stretch; cf. non-NMDA), than by current injected into the soma. Thus NMDA receptors activated by ongoing synaptic input (not related to the stretch) would indirectly participate in lowering of the plateau threshold measured at the soma during muscle stretch, but only in as far as these receptors are electrotonically distant from the soma.
showed that graded activation of these currents was necessary (although not sufficient) for the production of steady-state firing in the secondary range, whereas these currents were not significantly activated at lower firing rates of the primary range. Even though the major conclusion by Granit et al. (1966a,b) was that the effects produced by injected and synaptic current added linearly, their illustrations clearly demonstrated that synaptic input markedly affected the steady firing in the secondary range, evoked by rectangular current pulses (and they indeed point this out in a different context) (Granit et al. 1966b). In particular, they showed that tonic excitatory synaptic input from muscle stretch or nerve stimulation (EPSPs) produced a steep secondary range firing in cells that did not otherwise display this range (Fig. 3 in Granit et al. 1966b). Furthermore, synaptic inhibition eliminated the secondary range (Fig. 5 in Granit et al. 1966b). If the steady inward current that assists in producing the secondary range firing (Schwindt and Crill 1982) is the same as the current that produces the plateaus, then we might indeed expect EPSPs (or IPSPs) to affect the transition frequencies between primary and secondary range firing, just as the plateau thresholds (point at which steep frequency jump initiated) are affected. We therefore investigated this problem in cells that did not show signs of plateau potentials (see METHODS and RESULTS). In so far as the steep slope initiated during our slow ramps can be associated with the classical secondary range measured at the end of several graded long-lasting rectangular current pulses (steady state), our findings indeed support the proposition that the same inward currents are responsible for the secondary range firing and the "plateau" current. Clearly this warrants further study, with the same experimental paradigms as in the original studies by Granit et al. (1966a,b).
1- and 9-nA conditions in Fig. 6). The conclusion that bistable firing might not be expected with strictly synaptic activation could explain why previous studies of motor units in awake rats and humans have only given limited evidence of this phenomena (see INTRODUCTION).
; Zajac and Young 1980) could have resulted from plateau activation, although this issue clearly needs further study (see companion paper; and Gorassini et al. 1998b). In as far as plateaus are controlled by brain stem neuromodulators, such as 5-HT (Eken et al. 1989; Hultborn and Kiehn 1992), there may be gain control over such amplification of motor unit firing at recruitment.
). Furthermore, human motor units often cease firing at a lower rate than they start at (e.g., Erim et al. 1996; Gorassini et al. 1998a), as we have seen in cats (Fig. 8), and this probably results from plateaus that are activated abruptly at recruitment and sustained until after de-recruitment, as we have already discussed in RESULTS (Figs. 1B and 8).
).
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ACKNOWLEDGEMENTS |
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We thank L. Grondahl and I. Kjær for expert technical assistance.
Funding was provided by the Danish Medical Research Council, the Michaelsen Foundation, the Alberta Heritage Foundation for Medical Research (for D. Bennett), the Canadian Medical Research Council (for B. Fedirchuk), and a grant from the Danish Research Academy (for M. Gorassini).
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APPENDIX |
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The motoneuron model of Booth and Rinzel (1995) can be used in predicting how the dendritic EPSPs lower the plateau threshold seen at the soma (for related computer models see Baginskas et al. 1993; Binder et al. 1996; Butrimas and Gutman 1981; Lee and Heckman 1996a). The Booth model has a soma compartment and a dendritic compartment separated by a coupling conductance (Gc; to approximate the electrotonic attenuation). We start by considering how the model applies to our data with spiking inactivated (QX314 results from Fig. 3). Referring to the simplified situation where the absolute plateau threshold seen at the dendrites (Vd) does not depend on whether it is reached by injected current or synaptic current (see DISCUSSION), the following relations can be derived, which do not rely on specific knowledge of the soma-dendritic conductances. Without EPSPs, we need to inject current to depolarize the soma by a certain amount (Vs) in order for the dendrites to depolarize to reach the dendritic plateau threshold (Vd). With EPSPs, to reach the same dendritic depolarization (Vd), we need to depolarize the soma less (by 
Vs), so that the current that passes through the coupling conductance to the dendrites (Gc Vs) equals the effective (dendritic) synaptic current from the EPSPs (Id = Gc Vs). Thus the EPSPs lower the plateau threshold seen at the soma by Vs = Id/Gc. This relation indicates that the plateau threshold seen at the soma should be lowered in proportion to the synaptic input (Id; as we see in Fig. 5), and this effect should be greater for cells with larger dendritic trees that are more electrotonically distant (i.e., smaller coupling conductance: Gc). Without QX314 this simple equation cannot obviously be derived (if spiking occurs); however, it still holds qualitatively, as we have found with simulations involving spiking (cf. equations of Booth and Rinzel 1995; unpublished computer simulations in Matlab). The only thing to keep in mind is that the threshold for firing must be modeled to increase with firing rate (Schwindt and Crill 1982), thus allowing the plateau threshold to be reached.
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FOOTNOTES |
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Address for reprint requests: D. Bennett, 513 HMRC, Division of Neuroscience, University of Alberta, Edmonton, Alberta T06G 2S2, Canada.
Received 26 September 1997; accepted in final form 17 June 1998.
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REFERENCES |
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Abstract
Introduction
Methods
Results
Discussion
References
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Y. Li, M. A. Gorassini, and D. J. Bennett Role of Persistent Sodium and Calcium Currents in Motoneuron Firing and Spasticity in Chronic Spinal Rats J Neurophysiol, February 1, 2004; 91(2): 767 - 783. [Abstract] [Full Text] [PDF]
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A. M. Taylor and R. M. Enoka Quantification of the Factors That Influence Discharge Correlation in Model Motor Neurons J Neurophysiol, February 1, 2004; 91(2): 796 - 814. [Abstract] [Full Text] [PDF]
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J. J. Kuo, R. H. Lee, M. D. Johnson, H. M. Heckman, and C. J. Heckman Active Dendritic Integration of Inhibitory Synaptic Inputs In Vivo J Neurophysiol, December 1, 2003; 90(6): 3617 - 3624. [Abstract] [Full Text] [PDF]
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T. V. Bui, S. Cushing, D. Dewey, R. E. Fyffe, and P. K. Rose Comparison of the Morphological and Electrotonic Properties of Renshaw Cells, Ia Inhibitory Interneurons, and Motoneurons in the Cat J Neurophysiol, November 1, 2003; 90(5): 2900 - 2918. [Abstract] [Full Text] [PDF]
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H Hultborn, M E. Denton, J Wienecke, and J B Nielsen Variable amplification of synaptic input to cat spinal motoneurones by dendritic persistent inward current J. Physiol., November 1, 2003; 552(3): 945 - 952. [Abstract] [Full Text] [PDF]
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C Westad, R H Westgaard, and C J De Luca Motor unit recruitment and derecruitment induced by brief increase in contraction amplitude of the human trapezius muscle J. Physiol., October 15, 2003; 552(2): 645 - 656. [Abstract] [Full Text] [PDF]
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D. Nozaki, N. Kawashima, Y. Aramaki, M. Akai, K. Nakazawa, Y. Nakajima, and H. Yano Sustained Muscle Contractions Maintained by Autonomous Neuronal Activity Within the Human Spinal Cord J Neurophysiol, October 1, 2003; 90(4): 2090 - 2097. [Abstract] [Full Text] [PDF]
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Y. Li and D. J. Bennett Persistent Sodium and Calcium Currents Cause Plateau Potentials in Motoneurons of Chronic Spinal Rats J Neurophysiol, August 1, 2003; 90(2): 857 - 869. [Abstract] [Full Text] [PDF]
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R. H. Lee, J. J. Kuo, M. C. Jiang, and C. J. Heckman Influence of Active Dendritic Currents on Input-Output Processing in Spinal Motoneurons In Vivo J Neurophysiol, January 1, 2003; 89(1): 27 - 39. [Abstract] [Full Text] [PDF]
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R. K. Powers and M. D. Binder Persistent Sodium and Calcium Currents in Rat Hypoglossal Motoneurons J Neurophysiol, January 1, 2003; 89(1): 615 - 624. [Abstract] [Full Text] [PDF]
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R. Cueva-Rolon, R. Delgado-Lezama, J. G. Raya, M. Raya, R. Tecuanhuey, and E. J. Munoz-Martinez Sustained Firing of Alpha and Gamma Hind Limb Motoneurons Induced by Stimulation of the Pudendal Nerve J Neurophysiol, December 1, 2002; 88(6): 3232 - 3242. [Abstract] [Full Text] [PDF]
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J. F. Prather, B. D. Clark, and T. C. Cope Firing Rate Modulation of Motoneurons Activated by Cutaneous and Muscle Receptor Afferents in the Decerebrate Cat J Neurophysiol, October 1, 2002; 88(4): 1867 - 1879. [Abstract] [Full Text] [PDF]
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T. G. Hornby, J. C. McDonagh, R. M. Reinking, and D. G. Stuart Effects of Excitatory Modulation on Intrinsic Properties of Turtle Motoneurons J Neurophysiol, July 1, 2002; 88(1): 86 - 97. [Abstract] [Full Text] [PDF]
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M. Gorassini, J. F. Yang, M. Siu, and D. J. Bennett Intrinsic Activation of Human Motoneurons: Possible Contribution to Motor Unit Excitation J Neurophysiol, April 1, 2002; 87(4): 1850 - 1858. [Abstract] [Full Text] [PDF]
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M. Gorassini, J. F. Yang, M. Siu, and D. J. Bennett Intrinsic Activation of Human Motoneurons: Reduction of Motor Unit Recruitment Thresholds by Repeated Contractions J Neurophysiol, April 1, 2002; 87(4): 1859 - 1866. [Abstract] [Full Text] [PDF]
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B. Mattei and A. Schmied Delayed and prolonged effects of a near threshold EPSP on the firing time of human {alpha}-motoneurones J. Physiol., February 1, 2002; 538(3): 849 - 865. [Abstract] [Full Text] [PDF]
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D F Collins, D Burke, and S C Gandevia Sustained contractions produced by plateau-like behaviour in human motoneurones J. Physiol., January 1, 2002; 538(1): 289 - 301. [Abstract] [Full Text] [PDF]
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D. J. Bennett, Y. Li, and M. Siu Plateau Potentials in Sacrocaudal Motoneurons of Chronic Spinal Rats, Recorded In Vitro J Neurophysiol, October 1, 2001; 86(4): 1955 - 1971. [Abstract] [Full Text] [PDF]
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D. J. Bennett, Y. Li, P. J. Harvey, and M. Gorassini Evidence for Plateau Potentials in Tail Motoneurons of Awake Chronic Spinal Rats With Spasticity J Neurophysiol, October 1, 2001; 86(4): 1972 - 1982. [Abstract] [Full Text] [PDF]
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S. C. Gandevia Spinal and Supraspinal Factors in Human Muscle Fatigue Physiol Rev, October 1, 2001; 81(4): 1725 - 1789. [Abstract] [Full Text] [PDF]
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D. F. Collins, D. Burke, and S. C. Gandevia Large Involuntary Forces Consistent with Plateau-Like Behavior of Human Motoneurons J. Neurosci., June 1, 2001; 21(11): 4059 - 4065. [Abstract] [Full Text] [PDF]
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S Krawitz, B Fedirchuk, Y Dai, L M Jordan, and D A McCrea State-dependent hyperpolarization of voltage threshold enhances motoneurone excitability during fictive locomotion in the cat J. Physiol., April 1, 2001; 532(1): 271 - 281. [Abstract] [Full Text] [PDF]
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J. F. Prather, R. K. Powers, and T. C. Cope Amplification and Linear Summation of Synaptic Effects on Motoneuron Firing Rate J Neurophysiol, January 1, 2001; 85(1): 43 - 53. [Abstract] [Full Text] [PDF]
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G. Svirskis, A. Gutman, and J. Hounsgaard Electrotonic Structure of Motoneurons in the Spinal Cord of the Turtle: Inferences for the Mechanisms of Bistability J Neurophysiol, January 1, 2001; 85(1): 391 - 398. [Abstract] [Full Text] [PDF]
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J.-F. Perrier, S. Mejia-Gervacio, and J. Hounsgaard Facilitation of plateau potentials in turtle motoneurones by a pathway dependent on calcium and calmodulin J. Physiol., October 1, 2000; 528(1): 107 - 113. [Abstract] [Full Text] [PDF]
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R. H. Lee and C. J. Heckman Adjustable Amplification of Synaptic Input in the Dendrites of Spinal Motoneurons In Vivo J. Neurosci., September 1, 2000; 20(17): 6734 - 6740. [Abstract] [Full Text] [PDF]
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M. Gorassini, T. Eken, D. J. Bennett, O. Kiehn, and H. Hultborn Activity of Hindlimb Motor Units During Locomotion in the Conscious Rat J Neurophysiol, April 1, 2000; 83(4): 2002 - 2011. [Abstract] [Full Text] [PDF]
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J. C. Rekling, G. D. Funk, D. A. Bayliss, X.-W. Dong, and J. L. Feldman Synaptic Control of Motoneuronal Excitability Physiol Rev, April 1, 2000; 80(2): 767 - 852. [Abstract] [Full Text] [PDF]
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K L Paroschy and S J Shefchyk Non-linear membrane properties of sacral sphincter motoneurones in the decerebrate cat J. Physiol., March 15, 2000; 523(3): 741 - 753. [Abstract] [Full Text] [PDF]
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R. K. Powers and M. D. Binder Summation of Effective Synaptic Currents and Firing Rate Modulation in Cat Spinal Motoneurons J Neurophysiol, January 1, 2000; 83(1): 483 - 500. [Abstract] [Full Text] [PDF]
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R. H. Lee and C. J. Heckman Paradoxical Effect of QX-314 on Persistent Inward Currents and Bistable Behavior in Spinal Motoneurons In Vivo J Neurophysiol, November 1, 1999; 82(5): 2518 - 2527. [Abstract] [Full Text] [PDF]
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M. Gorassini, D. J. Bennett, O. Kiehn, T. Eken, and H. Hultborn Activation Patterns of Hindlimb Motor Units in the Awake Rat and Their Relation to Motoneuron Intrinsic Properties J Neurophysiol, August 1, 1999; 82(2): 709 - 717. [Abstract] [Full Text] [PDF]
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J.-F. Perrier and J. Hounsgaard Ca2+-Activated Nonselective Cationic Current (ICAN) in Turtle Motoneurons J Neurophysiol, August 1, 1999; 82(2): 730 - 735. [Abstract] [Full Text] [PDF]
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R. H. Lee and C. J. Heckman Enhancement of Bistability in Spinal Motoneurons In Vivo by the Noradrenergic alpha 1 Agonist Methoxamine J Neurophysiol, May 1, 1999; 81(5): 2164 - 2174. [Abstract] [Full Text] [PDF]
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D. J. Bennett, H. Hultborn, B. Fedirchuk, and M. Gorassini Short-Term Plasticity in Hindlimb Motoneurons of Decerebrate Cats J Neurophysiol, October 1, 1998; 80(4): 2038 - 2045. [Abstract] [Full Text] [PDF]
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