Acute Spinal Cats Research Articles

Transplants of Neurotrophin-Producing Autologous Fibroblasts Promote Recovery of Treadmill Stepping in the Acute, Sub-Chronic, and Chronic Spinal Cat.

Adult cats show limited spontaneous locomotor capabilities following spinal transection, but recover treadmill stepping with body-weight-supported training. Delivery of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3) can substitute for body-weight-supported training, and promotes a similar recovery in a shorter period of time. Autologous cell grafts would negate the need for the immunosuppressive agents currently used with most grafts, but have not shown functional benefits in incomplete spinal cord injury models and have never been tested in complete transection or chronic injury models. In this study, we explored the effects of autologous fibroblasts, prepared from the individual cats and modified to produce BDNF and NT-3, on the recovery of locomotion in acute, sub-chronic and chronic full-transection models of spinal injury. Fourteen female cats underwent complete spinal transection at T11/T12. Cats were separated into four groups: sham graft at the time of injury, and BDNF and NT-3 producing autologous fibroblasts grafted at the time of injury, 2 weeks after injury, or 6 weeks after injury. Kinematics were recorded 3 and 5 weeks after cell graft. Additional kinematic recordings were taken for some cats until 12 weeks post-graft. Eleven of 12 cats with neurotrophin-producing grafts recovered plantar weight-bearing stepping at treadmill speeds from 0.3 to 0.8 m/sec within 5 weeks of grafting, whereas control cats recovered poor quality stepping at low speeds only (≤ 0.4 m/sec). Further, kinematic measures in cats with grafts were closer to pre-transection values than those for controls, and recovery was maintained up to 12 weeks post-grafting. Our results show that not only are autologous neurotrophin-producing grafts effective at promoting recovery of locomotion, but that delayed delivery of neurotrophins does not diminish the therapeutic effect, and may improve outcome.

Take Your PIC: Motoneuronal Persistent Inward Currents May Be Somatic as Well as Dendritic. Focus on “Facilitation of Somatic Calcium Channels Can Evoke Prolonged Tail Currents in Rat Hypoglossal Motoneurons”

Inputs to motoneurons can be amplified and prolonged by noninactivating conductances mediating “persistent inward currents” or PICs. These currents, first identified by [Schwindt and Crill (1977)][1], are generated through voltage-dependent channels that have been thought to be confined to the

Functional consequences of motor unit recruitment order reversals following spinal cord transection in cat

Motoneuron recruitment order determinations were made for acute, 2-week chronic, and 3-month chronic spinal cats by comparing cutaneous nerve stimulation thresholds for evoking single unit tibialis anterior (TA) electromyogram (EMG) spikes of different sizes. Recruitment order was largely (∼80%) orderly (small spikes recruited at lower stimulus intensities than large spikes) in acute and 3-month chronic spinal animals. However, in 2-week chronic spinal animals recruitment order was reversed, with large units more often recruited at lower stimulus intensities than small units (∼65%). Morphological analyses of TA muscle fibers suggested that fiber size changes were unlikely to account for the dramatic alterations in recruitment order results of the 2-week chronic spinal animals. Additional studies suggested that the recruitment order reversal in the 2-week chronic animals coincided with an enhanced reflex neural output (increased recruitment or reflex gain) for the flexion reflex which compensated for disuse atrophy related decreases in flexor muscle force generation capability in these animals. The data from 2-week chronic spinal animals represent a functionally significant example of deviation from the normal size principle of motoneuron recruitment order as the corresponding reflex gain increases can enhance the rapidity of motor function recovery (standing, locomotion) following spinal injury.

Coherent sympathetic nerve activity in different postganglionic nerves after spinal cord transection in the cat

In this study, simultaneous discharges were recorded in three nerves originating from different levels of the spinal cord and the correlation between them was analyzed in the absence of the synchronizing input from the brainstem. In acute spinal cats, significant coherence (up to 0.3) was found at low frequencies (<4 Hz) between the vertebral and cardiac nerves and between the vertebral and renal nerves. Coherent discharges were, however, unstable, intermittent, and occurred rarely. In most experiments, it took several hours of observation to capture such an episode. Intrathecal glutamate injections facilitated the occurrence of rhythmic slow waves, which were, however, not correlated. We conclude that spinal sympathetic networks are capable of low frequency synchronization of the activity in different sympathetic outputs.

Réflexes de flexion: mécanisme de leur exagération chez les patients paraplégiques

IntroductionIn paraplegic patients, the stimulation of flexor reflex afferents (FRA) induces the usual flexion reflex followed by a later response, probably responsible for the clinical effects. Method This review summarizes the evidence that the late response is a genuine late reflex related to the late flexion reflex described in the acute spinal cat after Dopa and then to the spinal stepping generator. Conclusion This shows that some elements of the spinal circuitry on which the generation of stepping rhythms relies in animals exist in man.

Urethral pudendal afferent-evoked bladder and sphincter reflexes in decerebrate and acute spinal cats

Electrical stimulation of the urethral sensory pudendal nerve in decerebrate or acute spinal cats was used to evoke micturition reflexes in animals that failed to respond to bladder distension. In the decerebrate animals, stimulation of urethral afferents evoked voiding characterized by a large bladder pressure increase coordinated with a simultaneous decrease in external urethral sphincter activity. In animals in which the spinal cord was transected between T10 and L6, electrical stimulation of the urethral afferents evoked small increases in bladder pressure that were insufficient to expel fluid but the contractions were coordinated with a decrease in external urethral sphincter activity. It was concluded that in addition to interacting with spinobulbospinal micturition pathways, urethral pudendal afferents may have direct access to a spinal circuitry that can coordinate bladder and sphincter activity.

Spinal 5-HT2 receptor-mediated facilitation of pudendal nerve reflexes in the anaesthetized cat.

1. 5-Hydroxytryptamine (5-HT) is intimately associated with central sympathetic and somatic control of the lower urinary tract. The sympathetic and somatic innervation of the lower urinary tract is conveyed through efferent axons of the hypogastric and pudendal nerves, respectively. 2. The present study examined the effects of 2,5-dimethoxy-4-iodophenylisopropylamine (DOI), a 5-HT2 receptor subtype-selective agonist, on evoked potentials recorded from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of afferent fibres in the pelvic and pudendal nerves, respectively. Various spinalization paradigms were employed to localize the site of action. All cats were pretreated with xylamidine (1 mg kg-1), a peripherally-restricted 5-HT2 receptor antagonist. 3. In acute spinal cats, DOI (0.01-3 mg kg-1, i.v.) reliably produced dose-dependent increases in the pudendal nerve reflex (to 228 +/- 31% of control). These increases were reversed by the 5-HT2 receptor-selective antagonist, LY53857 (0.3-3 mg kg-1, i.v.). On the other hand, in spinally-intact cats, DOI produced no significant changes in the pudendal reflex. However, within minutes of spinalization of DOI-pretreated cats, a marked increase (to 221 +/- 16% of control) in the pudendal reflex was observed which could be reversed by LY53857. No significant effects were observed on hypogastric reflexes in either acute spinal or spinally-intact cats following DOI administration. No effects were seen in either spinally-intact or acute spinal animals when LY53857 was administered as the initial drug. 4. These results indicate that activation of spinal 5-HT2 receptors facilitates pudendal reflexes. In spinally-intact cats, it is hypothesized that DOI activates supraspinal pathways that mediate inhibition of the pudendal reflexes and counteracts the facilitatory effects of spinal 5-HT2 receptor activation.

Restoration of extensor excitability in the acute spinal cat by the 5-HT2 agonist DOI

1. The decerebrate cat preparation with an intact spinal cord is characterized by a high degree of excitability in extensor motoneuron pools, which is eliminated by acute spinalization. Subtype-specific agonists for serotonin (5-HT) were investigated in terms of their effectiveness in restoring the extensor excitability following spinalization. 2. Our hypothesis was that 5-HT2 receptors have the primary role in enhancement of extensor reflex excitability, whereas 5-HT1A and 5-HT1B/D receptors are relatively unimportant. Reflex excitability was assessed from the tonic levels of force and electromyographic (EMG) output from the ankle extensors medial gastrocnemius (MG) and soleus (SOL), and from the reflex forces in both these muscles generated by ramp-and-hold stretches of MG. 3. Before spinal transection, MG and SOL usually exhibited a small amount of tonic background EMG activity and force output. Ramp-and-hold stretch of MG generated a large-amplitude reflex response. Spinal transection at the level of T10 virtually abolished tonic background activity in both extensors and greatly attenuated the MG stretch reflex. Ventral topical application of the selective 5-HT2A/2C agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane hydrochloride (DOI) restored the amplitude of the MG stretch reflex in a dose-dependent fashion. However, a considerable portion of the DOI-mediated restoration of MG stretch reflex force was due to elevation of tonic background force levels above previous intact cord levels. 4. The DOI-induced increase in extensor tonic background excitability and facilitation of MG stretch reflex were reversed by ventral topical administration of the selective 5-HT2 antagonist ketanserin. No increase in extensor excitability was observed in spinalized preparations after administration of either the 5-HT1A agonist (+-)-8-hydroxy-dipropylaminotetralin hydrobromide or the 5-HT1B/1D agonist 7-trifluoromethyl-4-(4 methyl-1-piperazinyl)-pyrrolo[1,2- a]quinoxaline maleate. These data strongly suggest that the DOI-induced facilitation of extensor stretch reflex and tonic activity in spinalized preparations is mediated through an action on spinal 5-HT2 receptors. 5. One important difference between the actions of DOI in spinalized versus intact states was that the DOI-induced tonic and reflex forces in the spinalized state were subject to irregular oscillations. In contrast, DOI did not noticeably affect the smoothness of reflex force generation in the intact state. This discrepancy was probably due to the effects of clasp knife inhibition from muscular free nerve endings, which have potent reflex actions in the spinalized but not intact states. Thus DOI elevated excitability levels but did not alter the effects of spinalization on stretch reflex patterns.

Evidence for a spinal stepping generator in man.

The existence of the central pattern generator (CPG) for locomotion in lower mammals has been clearly demonstrated by Brown I who showed that rhythmic stepping like activity observed in the acute spinal cat was not due to a succession of reflexes since it persisted after peripheral deafferentation of the distal stump of the spinal cord. The physiology of the CPG has been reappraised by Lundberg's group2,3 and then exten­ sively described in lower mammals.4,5 Spinal locomotor activity was mainly observed in acute spinal prepara­ tions after injection of cathecolaminergic drugs.2,4 Spinal locomotor activity was also observed in the chronic �inal cat but only if the cat was spinalized as a kitten or if the spinal section was immediately followed by daily training on a treadmill. 7 In the chronic trained adult spinal cat, clonidine (which is a cathecolaminergic drug) is not necessary to induce rhythmic activity but it improves its amplitude and its regularity.8 Similarly, spinal locomotor activity can be obtained in chronic spinal rats after transplanting embryonic cathecolaminer�ic cells below the level of the spinal transection.9,1 In the chronic spinal monkey, the existence of this CPG was first denied. I I This assertion has been rediscussed by the same group and has led to less clear cut interpretations of the results. 12 The presence of a CPG in man is still debated and the recent paper by Illisl3 asserts that it has not been unequivocally demonstrated, following complete trans­ ection in man. Usually, patients with a clinically complete spinal cord section clearly do not recover rhythmic alternating locomotor activity as expected, although encouraging results have been obtained recently by Dietz et al14 and Wernig et al15 and described in the review by Barbeau and Rossignol.16 In addition, our group brought out two significant arguments favouring the presence of a CPG in patients with clinically complete paraplegia. First, we demon­ strated that flexor reflexes in paraplegic patients are always related to the CPG network. 17 -19 Secondly we observed rhythmic spinal activity in a patient with a clinically complete spinal cord section (spinal myoclo­ nus)?O

Plasticity in spinal opioid control of lower urinary tract function in paraplegic cats.

Spinal cord injury disrupts micturition reflexes, which produces morbidity. The contribution of endogenous opioid systems to urinary retention were assessed in chronic spinal cats by administering the opioid receptor antagonist, naloxone (5-500 micrograms kg-1, i.p.), to unanesthetized paraplegic cats while monitoring lower urinary tract function and observing hind limb reflexes. While naloxone had no overt effect in acute spinal cats, in chronic spinal cats naloxone induced the release of large volumes of urine and produced marked hind limb hyper-reflexia. Prominent tachyphylaxis and tolerance to the effects of naloxone were evident. Immunohistochemical studies indicated a marked increase in leucine enkephalin and dynorphin in sacral spinal neurons. Together, these data indicate hyperactivity of the endogenous spinal opioid system following recovery from spinal cord injury and, furthermore, suggest that the spinal neural circuitry may become 'dependent' upon elevated levels of endogenous opioid peptides.

Reversal of the influence of group Ib afferents from plantaris on activity in medial gastrocnemius muscle during locomotor activity.

1. Rhythmic locomotor activity was evoked in clonidine-treated acute and chronic spinal cats, and the effect of stimulating group I afferents from the plantaris muscle on the timing and magnitude of bursts in medial gastrocnemius (MG) motoneurons was examined. 2. The locomotor rhythm was entrained when group I afferents in the plantaris nerve were electrically stimulated with trains of stimuli presented at rates above and below the intrinsic frequency of the rhythmic activity. During entrainment at rates higher than the intrinsic frequency, a burst of activity in ipsilateral MG motoneurons was initiated approximately 40 ms after the onset of each stimulus train. At lower rates of entrainment the onset of MG bursts preceded the onset of the stimulus trains, and each stimulus train had an excitatory effect on the MG burst with a latency in the range of 30-50 ms. A similar excitatory effect was observed when the stimulus trains were triggered at a preset delay after the endogenous generation of the MG bursts. 3. The excitatory action of plantaris group I afferents on the MG motoneurons was only seen during periods of locomotor activity. In the absence of rhythmic activity, the same stimulus trains reduced any ongoing tonic activity in MG motoneurons. 4. Vibration of the plantaris muscle to preferentially activate group Ia afferents neither entrained the locomotor rhythm nor increased the magnitude of the MG bursts. 5. We conclude that during locomotor activity, input from group Ib afferents of the plantaris muscle has an excitatory action on the system of interneurons generating the extensor bursts, i.e., on the extensor half-center of the central rhythm generator.(ABSTRACT TRUNCATED AT 400 WORDS)

Spinal locomotor activity in acutely spinalized cats induced by intrathecal application of noradrenaline.

In this study we present a method of intrathecal drug administration in the acute spinal cat. A thin tube introduced into the subarachnoid space below the spinal cord was used for local drug administration. Noradrenaline reduced short-latency and provoked long-latency reflexes following high threshold afferent stimulation. Topical application of noradrenaline to the spinal cord was also able to induce and maintain locomotion. Our results strengthen the notion that noradrenergic systems play an important role in motor control. In addition, the present report introduces a protocol in the acute spinal cat, which combine the benefits associated with direct application of drugs as used in vitro experiments with the advantages of using the well investigated in vivo cat spinal cord preparation.

The use of naloxone to facilitate the generation of the locomotor rhythm in spinal cats

The locomotor rhythm evoked by perineal stimulation in clonidine-treated acute and chronic spinal cats can be produced more easily when the opioid receptor antagonist naloxone is also administered. Naloxone increases the frequency of the locomotor rhythm and decreases the intensity of skin stimulation required for evoking the rhythm. A useful property of naloxone is that it can restore the locomotor rhythm when the rhythm wanes, thus prolonging the time period over which locomotor activity can be generated. Administration of naloxone without clonidine does not enable the locomotor rhythm to be generated by skin stimulation, but it does reduce the concentration of clonidine required for the expression of a robust rhythm and may increase the chance of a successful preparation. We conclude that naloxone is a useful pharmacological tool for studies on the locomotor pattern generator.

Inhibitory effects on flexor reflexes in patients with a complete spinal cord lesion.

The inhibitory effects on flexors of electrical stimulation of a distal peripheral nerve were investigated in 7 paraplegic patients having a complete spinal cord section. The stimuli (3-50 mA) were applied to the sural nerve. Their effects were investigated on: 1) the ipsi- and contralateral H reflex of the Tibialis Anterior (TA); 2) the continuous EMG activity reflexly elicited in TA by a sustained pinch of the foot and 3) on the reflexes evoked in TA by contralateral sural nerve stimulation. Sural nerve stimulation induced two peaks of facilitation of the ipsilateral TA H reflex that could be replaced by inhibition as the stimulus intensity was increased. The comparison of the effect on H reflexes and the EMG activity suggests presynaptic inhibition of Ia fibres at time intervals longer than 300 ms. The stimulation could depress the sustained EMG reflex activity and induce a period of silence whose duration increased with the intensity of the stimulation. As shown in a previous study, a sural nerve stimulation induced a reflex in TA with a prolonged (more than 130 ms) latency. This late reflex could be selectively inhibited by a contralateral sural nerve stimulation, probably at an interneuronal level. These results confirm that the late reflex in TA is similar to the one observed after Flexor Reflex Afferent (FRA) stimulation in the acute spinal cat with DOPA. In addition, they show that at least some part of the "half centre" organization which has been described in the acute spinal cat with DOPA is also present in the human spinal cord chronically deprived of supraspinal control.

Effect of naloxone on transmission in excitatory and inhibitory spinal reflex pathways

The effect of systemic administration of naloxone on transmission in hindlimb reflex pathways was investigated in acute low spinal cats by conditioning monosynaptic reflexes. A marked enhancement of excitatory effects from cutaneous, joint, group II and III muscle afferents was observed in posterior biceps and semitendinosus motoneurones in 4 out of 6 experiments. In contrast, inhibitory synaptic effects in gastrocnemius and soleus motoneurones were not enhanced except weakly in one experiment. The effects of naloxone are different from those observed after spinal cord lesions interrupting axons of a previously described group of upper lumbar propriospinal neurones, which tonically suppress reflex transmission in the acute low spinal state. It is postulated that the suppression exerted by this group of neurones is not dependent on endogenous opioid peptides.

Effects of flexor reflex afferent stimulation on the soleus H reflex in patients with a complete spinal cord lesion: evidence for presynaptic inhibition of Ia transmission

The effects of electrically stimulating the Flexor Reflex Afferent (FRA) on the soleus H reflexes were investigated in 34 paraplegic patients having a clinically complete spinal cord lesion. Conditioning stimuli (5-50 mA) were applied to the ipsilateral or contralateral sural nerve. The conditioning-test interval ranged from 20 to 1000 ms. A late ipsilateral flexor reflex (EMG) was found in all patients. A late contralateral extension reflex was sporadically observed in only 3 patients. The excitability curves usually showed two phases of ipsilateral H reflex inhibition and contralateral H reflex facilitation, one between 50 and 130 ms and the other after over 200 ms. These intervals correspond to early and late flexion reflexes. With high intensity stimulation the early and late ipsilateral inhibition fused. An early low threshold ipsilateral facilitation occurred in 9 patients. The contralateral late facilitation was followed by prolonged inhibition in 10 patients. Changes in presynaptic inhibition were assessed by measuring the heteronymous monosynaptic Ia facilitation from quadriceps to soleus. For methodological reasons, it was only possible to investigate the effect of contralateral conditioning volleys which was performed in 5 patients. A significant and regular reduction of the heteronymous Ia facilitation was found in 4 patients. The reduction is taken to indicate that the FRA evokes presynaptic inhibition of Ia transmission to alpha motoneurones. Presynaptic inhibition was also indicated by the enhancement of a vibratory stimulus induced inhibition in 2 subjects. These results are consistent with the hypothesis that the reflex organization in patients with a spinal cord section is similar to that of the acute spinal cat injected with DOPA.

Mechanisms underlying the recovery of urinary bladder function following spinal cord injury

Micturition in cats and rats with an intact neuraxis is dependent upon a spinobulbospinal reflex activated by Aδ bladder afferents. This report describes changes in micturition reflexes 2 h to 14 weeks following spinal cord transection at the lower thoracic level. In acute spinal cats micturition reflexes were blocked, however, several weeks after transection, a long latency (180–200 ms) spinal reflex could be activated by C-fiber bladder afferents. This reflex was blocked by capsaicin in doses (20–30 mg/kg, s.c.) that did not affect micturition reflexes in intact cats. Micturition reflexes were unmasked in acute spinal and facilitated in chronic spinal cats by naloxone, an opioid antagonist. Spinal neurons and axons containing opioid peptides were more prominent below the level of transection in chronic spinal cats. VIP, a putative neurotransmitter in C-fiber bladder afferents, inhibited micturition reflexes when injected intrathecally (2–10 μg) in intact cats but facilitated micturition reflexes in spinal cats (doses 0.1–1 μg, i.t.). VIP-containing C-fiber afferent projections to lamina 1 of the sacral spinal cord expanded in spinal cats. Thus VIP afferents may have an important role in the recovery of bladder reflexes after spinal injury. Paraplegic animals also exhibit bladder-sphincter dyssynergia, which causes functional outlet obstruction. Studies in rats have revealed that outlet obstruction induced by partial urethral ligation facilitates spinal micturition reflex pathways and causes an expansion of HRP-labelled bladder afferent projections in the spinal cord. These findings raise the possibility that the alterations in central reflex connections in paraplegic animals may be induced in part by changes in peripheral afferent input secondary to outlet obstruction. In summary, recovery of bladder function in paraplegic animals is associated with a major reorganization of reflex connections and neurotransmitter mechanisms in the spinal cord. It appears that this reorganization involves morphological as well as functional changes.

Late flexion reflex in paraplegic patients. Evidence for a spinal stepping generator

We demonstrated previously that electrical stimulation of the Flexor Reflex Afferents (FRA) induces a late flexion reflex with a central conduction time longer than 100 msec. Its latency is prolonged by increasing the intensity or the duration of the stimulation. This late reflex is therefore similar to the late flexion reflex observed in acute spinal cat with DOPA. Some findings suggest that in man the late flexion reflex could be inhibited at a premotoneuronal level by contralateral FRA stimulation. In relation to the late flexion reflex, a late contralateral facilitation of soleus monosynaptic reflex (MSR) was observed. Rhythmical activity was observed in only one patient who had an exceptional form of spinal myoclonus. This myoclonus could be modulated by FRA stimulation. These facts show that the reflex organization in paraplegic patients is similar to the one described in acute spinal cat with DOPA and therefore suggest that a spinal stepping generator could exist in humans.

Tonic suppression of reflex transmission in low spinal cats.

Transmission in various spinal hindlimb reflex pathways arising from muscle, cutaneous and joint afferents, was investigated in acute low spinal (Th10) cats before and after lesions at more caudal levels in the lumbar segments. Lesions of the ipsilateral dorsolateral funiculus (DLF) resulted in increased mono- and polysynaptic ventral root discharges. With conditioning of monosynaptic reflexes it was demonstrated that the DLF lesion enhanced transmission in reflex pathways from group II and III muscle afferents. The DLF lesion also resulted in increased dorsal root potentials from cutaneous, joint and group III muscle afferents. These reflex enhancements could not be obtained with lesions rostral to L2, but developed with lesions in L2 and to some extent in L3, but no further effect was obtained by adding lesions caudal to L3. Ventral extension of the DLF lesion gave hardly any increase of reflex transmission. It is postulated that the investigated reflex pathways may be tonically inhibited in the acute low spinal state by propriospinal neurones with cell bodies in the L2-L3 segments and with axons descending in the dorsolateral funiculus.

Bistability of alpha‐motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5‐hydroxytryptophan.

1. In the preceding paper (Crone, Hultborn, Kiehn, Mazieres & Wigström, 1988) it was shown that a short-lasting synaptic excitation ('on' stimulus) of extensor motoneurones (primarily triceps surae) in the decerebrate cat often resulted in a maintained excitability increase, which could be reset by a short-lasting inhibitory stimulus train ('off' stimulus). In the present experiments intracellular recording from triceps surae motoneurones and the electroneurogram (ENG activity) from triceps surae nerve branches were performed in parallel. 2. Sustained firing of individual triceps surae motoneurones was most often recorded in parallel with the maintained ENG activity following a synaptic 'on' stimulus. When the motoneurone was silenced, by a hyperpolarizing current through the microelectrode, there was no sign of on-going synaptic excitation during the maintained ENG activity following an 'on' stimulus. It was therefore suggested that voltage-dependent intrinsic properties of the motoneurones themselves could be responsible for the maintained firing. 3. In confirmation of this hypothesis it was found that short-lasting depolarizing current pulses through the recording microelectrode could trigger a self-sustained firing in the motoneurone provided that the bias current (i.e. the holding potential) was kept within certain limits. Hyperpolarizing current pulses terminated the firing. When the spike-generating mechanism was inactivated (by long-lasting excessive depolarization) similar depolarizing and hyperpolarizing current pulses could initiate and terminate plateau potentials in the motoneurones. By grading the depolarizing current pulses it was found that the plateau potentials were of all-or-none character, typically around 10 mV in amplitude. The two levels of excitability which can be triggered by short-lasting excitation and inhibition of the motoneurones is referred to as 'bistable' behaviour of the motoneurones. 4. After an acute spinal transection, in the unanaesthetized cat, the bistable behaviour of the motoneurones disappeared. However, it reappears following intravenous injection of the serotonin precursor 5-hydroxytryptophan (50-120 mg/kg). 5. Individual triceps surae motor units were recorded by selective EMG electrodes during tonic stretch reflexes in the decerebrate preparations. Based on an analysis of their firing pattern during lengthening and shortening (or vibration) of the muscle it is suggested that plateau potentials in motoneurones are recruited during the tonic stretch reflex. Furthermore, it is argued that a quantitatively important part of the depolarization of motoneurones during the tonic stretch reflex indeed originates from these plateau potentials.(ABSTRACT TRUNCATED AT 400 WORDS)