Spinal Rhythm Generator Research Articles

Lumbar multiunit activity power spectrum during air stepping in the spinal cat: evidence for a flexor-dominated rostrocaudally distributed locomotor center.

Clues about the organization of spinal networks responsible for rhythmic motor behaviors have come from the examination of reflex circuitry, lesioning studies, and single-cell recordings. Recently, more attention has been paid to extracellularly recorded multiunit signals thought to represent the general activity of local cellular potentials. Focusing on the gross localization of spinal locomotor networks, we used multiunit signals of the lumbar cord to classify the activation and organization of those networks. We employed power spectral analysis to compare multiunit power across rhythmic conditions and locations and to infer patterns of activation based on coherence and phase measures. We found greater multiunit power in midlumbar segments during stepping, supportive of previous lesioning studies isolating rhythm-generating capabilities to these segments. We also found much greater multiunit power during the flexion phase of stepping than during the extension phase for all lumbar segments. Greater multiunit power at flexion indicates increased neural activity during this phase and is suggestive of previously reported asymmetries between flexor- and extensor-related interneuronal populations of the spinal rhythm-generating network. Finally, the multiunit power showed no phase lag at coherent frequencies throughout the lumbar enlargement indicative of a longitudinal standing wave of neural activation. Our results suggest that the multiunit activity may be representative of the spinal rhythm-generating activity that is distributed in a rostrocaudal gradient. Additionally, our results indicate that this multiunit activity may operate as a flexor-dominant standing wave of activation that is synchronized throughout the rostrocaudal extent of the lumbar enlargement.NEW & NOTEWORTHY We report on the power spectral analysis of multiunit activity (MUA) of lumbar spinal interneurons during a locomotor task. In line with prior studies, we found evidence of greater power at the frequency of locomotion in high lumbar segments and during the flexion phase. Our results also confirm prior observations from our laboratory that the rhythmically active MUA behaves as a longitudinal standing wave of neural activation that is flexor dominant.

Spinal Rhythm Generation by Step-Induced Feedback and Transcutaneous Posterior Root Stimulation in Complete Spinal Cord–Injured Individuals

Background. The human lumbosacral spinal circuitry can generate rhythmic motor output in response to different types of inputs after motor-complete spinal cord injury. Objective. To explore spinal rhythm generating mechanisms recruited by phasic step-related sensory feedback and tonic posterior root stimulation when provided alone or in combination. Methods. We studied stepping in 4 individuals with chronic, clinically complete spinal cord injury using a robotic-driven gait orthosis with body weight support over a treadmill. Electromyographic data were collected from thigh and lower leg muscles during stepping with 2 hip-movement conditions and 2 step frequencies, first without and then with tonic 30-Hz transcutaneous spinal cord stimulation (tSCS) over the lumbar posterior roots. Results. Robotic-driven stepping alone generated rhythmic activity in a small number of muscles, mostly in hamstrings, coinciding with the stretch applied to the muscle, and in tibialis anterior as stance-phase synchronized clonus. Adding tonic 30-Hz tSCS increased the number of rhythmically responding muscles, augmented thigh muscle activity, and suppressed clonus. tSCS could also produce rhythmic activity without or independent of step-specific peripheral feedback. Changing stepping parameters could change the amount of activity generated but not the multimuscle activation patterns. Conclusions. The data suggest that the rhythmic motor patterns generated by the imposed stepping were responses of spinal reflex circuits to the cyclic sensory feedback. Tonic 30-Hz tSCS provided for additional excitation and engaged spinal rhythm-generating networks. The synergistic effects of these rhythm-generating mechanisms suggest that tSCS in combination with treadmill training might augment rehabilitation outcomes after severe spinal cord injury.

Mechanisms of rhythm generation of the human lumbar spinal cord in response to tonic stimulation without and with step-related sensory feedback

Independent studies have shown that the human lumbar spinal networks below a complete spinal cord injury can produce rhythmic motor outputs in response to step- related sensory feedback or sustained electrical spinal cord stimulation (SCS). Here we present our current studies ap- plying lumbar SCS in motor-complete spinal cord injured (SCI) individuals in the supine and supported standing posi- tion, and during assisted treadmill stepping, to explore the mechanisms of spinal rhythm generation. SCS could pro- duce rhythmic EMG activities without step-related sensory feedback; in each case, all muscles were active with a com- mon rhythm frequency. During SCS and passive treadmill stepping, muscle activities were normally synchronized to the imposed step frequency, but activities with an independ- ent rhythm frequency were generated as well. The results suggest rhythmic reflex actions and central spinal generation as two different causes of rhythm generation. Here, we present our current studies that explore the roles of sustained inputs and step-related sensory feedback to the human lumbosacral spinal cord in the generation of rhythmic motor patterns. We applied epidural or transcu- taneous lumbar SCS in motor-complete SCI individuals in the supine position (preventing hip extension and axial limb load that are otherwise critical for rhythm genera- tion), in a supported standing positions with the lower limbs being 'mechanically immobilized' (preventing movements at hip and knee), and during assisted and body-weight supported (BWS) treadmill stepping. Based on their characteristically different signal profiles, the hypothesis was that the non-patterned and patterned inputs to the spinal cord neural networks would reveal different mechanisms of rhythm generation. Methods

Effect of intrathecal administration of serotoninergic and noradrenergic drugs on postural performance in rabbits with spinal cord lesions.

Our previous studies have shown that extensive spinal lesions at T12 in the rabbit [ventral hemisection (VHS) or 3/4-section that spares one ventral quadrant (VQ)] severely damaged the postural system. When tested on the platform periodically tilted in the frontal plane, VHS and VQ animals typically were not able to perform postural corrective movements by their hindlimbs, although EMG responses (correctly or incorrectly phased) could be observed. We attempted to restore postural control in VHS and VQ rabbits by applying serotoninergic and noradrenergic drugs to the spinal cord below the lesion through the intrathecal cannula. It was found that serotonin and quipazine (5-HT1,2,3 agonist) did not re-establish postural corrective movements. However, when applied during a 10-day period after lesion, these drugs produced a twofold increase of the proportion of correct EMG responses to tilts. It was also found that methoxamine (alpha1 noradrenergic agonist), as well as the mixture of methoxamine and quipazine, did not re-establish postural corrective movements and did not increase the proportion of correct EMG responses. Serotonin (at later stages) and methoxamine induced periodical bursting in EMGs, suggesting activation of spinal rhythm-generating networks. Appearance of bursting seems to perturb normal operation of postural mechanisms, as suggested by methoxamine-induced abolishment of postural effects of quipazine. When applied in an intact animal, none of the tested drugs affected the value of postural corrections or evoked periodical bursting. We conclude that activation of the serotoninergic system (but not the noradrenergic one) causes selective enhancement of spinal postural reflexes during the earlier postlesion period.

In restless legs syndrome, during changes in vigilance, the forced EEG shifts from alpha activity to delta or high alpha may lead to the altered states of dopamine receptor function and the symptoms

RLS cases may carry a genetic vulnerability called EEG alpha activity gate dyscontrols which appear during changes in vigilance and generally during sleep. It is triggered by forced EEG shifts either from alpha activity to delta or high alpha. Expressions of alpha activity gate dyscontrols may have a gate effect that trigger a second vulnerability-dopamine receptor specific individual sensitivity (DRSIS) and this leads to a deficiency in dopamine transmissions at diencephalospinal dopamine system (DSDS). Due to altered gene expressions in states of dopamine receptor function, DRSIS EEGs and RLS symptoms may be interpreted as follows: A. Disinhibition state is alpha activity gate dyscontrols induced inhibition of DSDS inhibitory dopamine modulations. Dopaminergic disinhibitions inhibit inhibitory interneurons of sensory and motor nuclei neurons that are involved in RLS. These sleep sensitive inhibitory interneurons possibly have GABA-ergic functions in sleep. (I) DSDS thalamic neurons' disinhibitory effects in thalamus on GABA-ergic interneurons of: (a) Intralaminar nuclei non-discriminative sensation neurons at thalamocortical premotor network leading to symptom of "a sense of urgency to move" generally referenced to legs.(b) Reticular thalamic nucleus (RTN) neurons. At polysomnography,during NREM sleep, disinhibited RTN neurons show alpha activity gate dyscontrol 1. These are recurrent subtypes of CAP in alpha band (7-12 Hz) pointing a difficulty in shifting to subtypes of CAP in low delta bands (0.25-2.5 Hz) and sleep fragmentations.(II) Supraspinal disinhibitory projections from DSDS thalamic neurons on GABA-ergic interneurons of: (a) Sensory neurons at posterior horns of spinal cord leading to dysesthesias, generally referenced to legs.(b) Medullary-reticulospinal neurons and by way of independent spinal rhythm generators on motoneurons leading to periodic limb movements in sleep.B. Activation state is an increase in symptoms. Sensory intralaminar and motor pontin nuclei neurons are in fact excitatory but are disinhibited in RLS. Due to altered gene expression, these neurons begin to perceive 'disinhibition' as reduced inhibition. Their glutamate receptors may activate deficient dopamine transmissions on RTN leading to alpha activity gate dyscontrol 2. This implies a failure in preventing shifts to frequent subtypes of CAP in high alpha and low beta bands (12-13 Hz) resulting in an increase of sensorimotor symptoms and appearance of motor restlessness, behavioral arousals and insomnia. C. Inhibition state is spontaneous relief from sensorimotor symptoms. Short or long-term synaptic plasticities of dopamine receptors towards activations initiate negative feedbacks from inhibitory interneurons. They are supported by inhibitory dopamine modulations- alertness and some awareness generally with regular high alpha EEGs, supraspinal inhibitions and a reverse movement pattern of PLMS during standing up and continuing to walk.

Rhythmic phrenic, intercostal and sympathetic activity in relation to limb and trunk motor activity in spinal cats

During l-DOPA-induced fictive spinal locomotion rhythmic activities in nerves to internal intercostal and external oblique abdominal muscles and in phrenic and sympathetic nerves were observed which were always coordinated with locomotor activity in forelimb and hindlimb muscle nerves. A periodicity with longer lasting tonic phases could be induced by cutaneous nerve stimulation or asphyxia. This activity was observed in limb motor nerves as well as in respiratory motor and sympathetic nerves. A slow independent activity of the phrenic and intercostal nerves or the sympathetic nerves, which could be related to a normal respiratory rhythm or independent sympathetic rhythms was not observed. The findings indicate that during fictive spinal locomotion the activity of spinal rhythm generators for locomotion also projects onto respiratory and sympathetic spinal neurones.

Alpha1-adrenergic receptor-induced slow rhythmicity in nonrespiratory cervical motoneurons of neonatal rat spinal cord.

Previous studies have reported that the alpha1-adrenergic system can activate spinal rhythm generators belonging to the central respiratory network. In order to analyse alpha1-adrenergic effects on both cranial and spinal motoneuronal activity, phenylephrine (1-800 microM) was applied to in vitro preparations of neonatal rat brainstem-spinal cord. High concentration of phenylephrine superfusion exerted multiple effects on spinal cervical outputs (C2-C6), consisting of a lengthening of respiratory period and an increase in inspiratory burst duration. Furthermore, in 55% of cases a slow motor rhythm recorded from the same spinal outputs was superimposed on the inspiratory activity. However, this phenylephrine-induced slow motor rhythm generated at the spinal level was observed neither in inspiratory cranial nerves (glossopharyngeal, vagal and hypoglossal outputs) nor in phrenic nerves. Whole-cell patch-clamp recordings were carried out on cervical motoneurons (C4-C5), to determine first which motoneurons were involved in this slow rhythm, and secondly the cellular events underlying direct phenylephrine effects on motoneurons. In all types of motoneurons (inspiratory and nonrespiratory) phenylephrine induced a prolonged depolarization with an increase in neuronal excitability. However, only nonrespiratory motoneurons showed additional rhythmic membrane depolarizations (with spiking) occurring in phase with the slow motor rhythm recorded from the ventral root. Furthermore the tonic depolarization produced in all motoneurons results from an inward current [which persists in the presence of tetrodotoxin (TTX)] associated with a decrease in neuron input conductance, with a reversal potential varying as a Nernstian function of extracellular K+ concentration. Our results indicate that the alpha1-adrenoceptor activation: (i) affects both the central respiratory command (i.e. respiratory period and inspiratory burst duration) and spinal inspiratory outputs; (ii) induces slow spinal motor rhythmicity, which is unlikely to be related to the respiratory system; and (iii), increases motoneuronal excitability, probably through a decrease in postsynaptic leak K+ conductance.

The distribution of NADPH-diaphorase-labelled interneurons and the role of nitric oxide in the swimming system of Xenopus laevis larvae.

The possible involvement of the free radical gas nitric oxide (NO) in the modulation of spinal rhythm-generating networks has been studied using Xenopus laevis larvae. Using NADPH-diaphorase histochemistry, three putative populations of nitric oxide synthase (NOS)-containing cells were identified in the brainstem. The position and morphology of the largest and most caudal population suggested that a proportion of these neurons is reticulospinal. The possible contribution of nitrergic neurons to the control of swimming activity was examined by manipulating exogenous and endogenous NO concentrations in vivo with an NO donor (SNAP, 100-500 micromol l(-)(1)) and NOS inhibitors (l-NAME and l-NNA, 0.5-5 mmol l(-)(1)), respectively. In the presence of SNAP, swim episode duration decreased and cycle period increased, whereas the NOS inhibitors had the opposite effects. We conclude from these data that the endogenous release of NO from brainstem neurons extrinsic to the spinal cord of Xenopus laevis larvae exerts a continuous modulatory influence on swimming activity, functioning like a 'brake'. Although the exact level at which NO impinges upon the swimming rhythm generator has yet to be determined, the predominantly inhibitory effect of NO suggests that the underlying mechanisms of NO action could involve modulation of synaptic transmission and/or direct effects on neuronal membrane properties.

Flexor reflex afferents reset the step cycle during fictive locomotion in the cat.

The generation of locomotor-like spinal rhythms has been proposed to involve two neural centres with mutual reciprocal inhibition (Graham Brown's "half-centre" hypothesis). Much later a particular set of segmental flexor reflex pathways were described as being organized in accordance with this half-centre hypothesis. As these pathways became operative following injection of monoaminoxidase inhibitors and L-3,4-dihydroxyphenylalanine (L-dopa), i.e. under the same conditions under which a spontaneous locomotor activity may develop, it was assumed that these particular pathways and spinal rhythm generators involve the same neuronal networks. In order to give further evidence to this hypothesis, we investigated whether short trains to "flexor reflex afferents" (FRA) reset the spinal locomotor rhythm, i.e. shorten or lengthen the stimulated cycle after which the regular rhythm is resumed with step cycles of the original duration. The experiments were performed in anaemically decapitated, high-spinal curarized cats. A steady locomotor rhythm was induced by injection of nialamide and L-dopa and the influence of electrical stimulation (trains of 50-1000 ms) of FRA (joint, cutaneous, and group II and III muscle afferents) onto this rhythm was tested. Stimulation of FRA induced a clear resetting of the locomotor rhythm, which was mainly characterized by a flexion reflex pattern: during the extension phase the extensor activity was interrupted and a flexion phase was initiated; during the late flexion phase mainly a prolongation of that phase with a variable change of the following extension phase was induced. In addition to this prevailing pattern, stimulation of some nerves (in particular nerves to more distal extensors and the sural nerve) could often prolong extension, when stimulated during the late extension, or terminate the flexor burst and initiate a new extension phase, when stimulated during the late flexion phase. This pattern is probably due to the concomitant stimulation of group I afferents in the case of the muscle nerves and to separate non-FRA pathways in the case of the sural nerve. The results demonstrate that the interneurones of the FRA pathways, which are operative during L-dopa-induced locomotion in spinal animals, can be considered as neuronal elements of the rhythm-generating network for locomotion.

Synchronization of somato-sympathetic outflows during exercise: role for a spinal rhythm generator.

The synchronization of somatic motor outflow and sympathetic efferent activity during exercise has important functional consequences. For example, a certain degree of sympathetic vasoconstriction to active skeletal muscle vascular beds may be required to prevent an excessive decrease in vascular resistance during intense dynamic exercise involving a large skeletal muscle mass. Moreover, the redistribution of blood flow away from non-exercising vascular beds to contracting skeletal muscles is necessary to meet their increased metabolic demands. Historically, the nervous system has been separated arbitrarily into a volitional (somatic) and a reflex (autonomic) control system that does not necessitate volitional input (Koizumi & Brooks, 1972). However, during exercise this partition of the somatic and autonomic control systems is replaced by an overlapping control system that influences both somatic and sympathetic outflows in a parallel fashion. Previous work has suggested that the integration and co-ordination of the somatic and sympathetic motor responses during exercise were mediated by a supraspinal neural mechanism referred to as central command (Waldrop et al. 1996). However, there is an accumulating body of evidence, including papers on the role of the spinal cord in the regulation of sympathetic outflow (Weaver & Stein, 1989), suggesting that rhythmic neural activity destined for somatomotor and sympathetic outflows may be under the control of intrinsic neuronal circuitry in the spinal cord. In this issue of The Journal of Physiology, the paper by Chizh et al. (1998) demonstrates for the first time that some components of somatic motor and sympathetic neural outflows are synchronized by a spinal mechanism. The authors studied the relationship between sympathetic and somatic motor outflows from the thoraco-sacral spinal cord using an isolated trunk-hindquarters preparation of the adult mouse. They found that some of the activity in both somatic and sympathetic outflows was coupled. However, since there was also sympathetic neural activity that showed burst discharges in the absence of somatic motor activity, the spinal mechanism responsible for generating sympathetic burst activity was not the same mechanism that was responsible for somato-sympathetic coupling. Therefore, there remained spinal mechanisms that were capable of generating bursting activity independently of somatic and sympathetic activities. When NMDA was added to the perfusate to induce rhythmic somatic motor activity, a dose-dependent bursting pattern in sympathetic efferent and somatic motor nerves was evoked that was coupled at similar frequencies. Correlational analyses found a strong coherence between somatic motor outflow and sympathetic efferent discharge when triggered from peaks in somatic motor activity. However, this synchronization was not found when triggered from the peaks of sympathetic discharge. This finding led Chizh et al. (1998) to hypothesize that the generating mechanism responsible for somatic locomotor activity was the same mechanism responsible for coupling somatic outflow to sympathetic activity. These findings support the notion that the spinal cord possesses the necessary neuronal ‘machinery’ for generating and coupling sympathetic discharge with somatic motor outflow independently of supraspinal structures (i.e. the spinal rhythm generator represents a spinal central command). Important adjustments occur in the heart and blood vessels during exercise in order to provide the appropriate oxygen delivery to match the metabolic demand of contracting skeletal muscle. The coupling of somatic motor and sympathetic outflows is mediated by supraspinal neural mechanisms (supraspinal central command) in humans and animals (Fig. 1). In humans, intense intermittent static exercise produced a one-to-one synchronization of somatic motor activity with muscle sympathetic nerve activity that was purportedly directed to skeletal muscle vasculature (Victor et al. 1995). This synchronization persisted in the presence of both partial neuromuscular blockade (i.e. to increase central command) and after local anaesthetic block of the arm nerves to eliminate afferent feedback from skeletal muscle. Likewise, electrical and chemical stimulation of the hypothalamic locomotor region in decorticate cats after neuromuscular blockade evokes fictive locomotion that produces increases in arterial blood pressure (Waldrop et al. 1996) and synchronization of sympathetic nerve activity with hindlimb motor nerve activity (Hajduczok et al. 1991). And, as seen in humans, the synchronization of somatic motor activity and sympathetic discharge was unaffected by peripheral feedback mechanisms. These findings suggest that central command signals of supraspinal origin can regulate and co-ordinate sympathetic and somatomotor outflows during exercise. Figure 1 Synchronization of somatic motor outflow and sympathetic efferent activity during exercise is mediated by supraspinal and spinal mechanisms. The important work of Chizh et al. (1998) extends our understanding of the synchronization of somatic motor activity and sympathetic outflow by highlighting the role of a spinal somato-sympathetic generator (Fig. 1). Also, the coupling of somato-sympathetic neural outflows in the spinal cord may represent an exquisite mechanism to finely tune sympathetic discharge to the segmental level of somatic motor outflow during exercise. Finally, {fontsize the degree to which supraspinal central command signals influence the somato-sympathetic spinal generator needs to be studied to further our understanding of somato-sympathetic coupling during volitional exercise.

Aminergic modulation of glycine release in a spinal network controlling swimming in Xenopus laevis.

1. Neuromodulators can effect changes in neural network function by strengthening or weakening synapses between neurons via presynaptic control of transmitter release. We have examined the effects of two biogenic amines on inhibitory connections of a spinal rhythm generator in Xenopus tad poles. 2. Glycinergic inhibitory potentials occurring mid-cycle in motoneurons during swimming activity are reduced by 5-hydroxytryptamine (5-HT; serotonin) and enhanced by noradrenaline (NA). These opposing effects on inhibitory synaptic strength are mediated presynaptically where 5-HT decreases and NA increases the probability of glycine release from inhibitory terminals. 3. The amines also have contrasting effects on swimming: 5-HT increased motor burst durations while NA reduced swimming frequency. Aminergic modulation of glycinergic transmission may thus control fundamental parameters of swimming and force the spinal network to generate opposite extremes of its spectrum of possible outputs.

Interactions between the neural networks for escape and swimming in goldfish

Interactions between neural networks for different motor behaviors occur frequently in nature; however, there are few vertebrate models for studying these interactions. One potentially useful model involves the interactions between escape and swimming behaviors in fish. Fish can produce escape bends while swimming, using some of the same axial muscles for both behaviors. Here we study the interactions between escape and swimming in a paralyzed goldfish preparation in which we can activate the networks for both behaviors. Fictive swimming was elicited by electrical stimulation in the midbrain locomotor region. During the swimming, we fired a single action potential in the reticulospinal Mauthner (M) cell, which initiates the escape behavior (Zottoli, 1977). Firing the M cell overrode the swimming motor output to produce an output appropriate for escape regardless of the phase of swimming at which it was fired. The M cell also could reset the swimming rhythm dramatically in a way that led to a smooth transition from an escape bend to one side into subsequent swimming. Both the override and reset supported predictions based on previous studies of the organization of the M-cell network. They apparently allow for a well coordinated motor output when a fish must produce an escape while swimming. The potent effects of one action potential in a single, identifiable reticulospinal neuron make this an attractive model system for future studies of the cellular basis of interactions between descending pathways and spinal rhythm-generating networks.

The influence of premotor interneuron populations on the frequency of the spinal pattern generator for swimming in Xenopus embryos: a simulation study.

Our aim was to test the hypothesis that the frequency of neuronal rhythm-generating networks is partly controlled by the size of the active premotor interneuron population. We have tested possible mechanisms for frequency changes in a population model of the Xenopus laevis embryo spinal rhythm-generating networks for swimming. After initiation by a brief sensory excitation, the frequency of swimming activity decreases to a steady level determined by the properties of the 24 interneurons and their connections. The initial frequency decrease was dependent on the time-course of initiating sensory synaptic excitation. When some premotor excitatory interneurons were given weaker synaptic connections to reflect the variability in the spinal cord, they could drop out and stop firing during the initial frequency decrease while swimming activity continued. If the synaptic input of such weak excitatory interneurons was graded finely, they could drop out consecutively. This led to further decreases in the level of tonic excitation and in network frequency which depended on the number, type and distribution of excitatory interneurons that stopped firing. Silent weak excitatory interneurons could be recruited by a second sensory excitation and cause an increase in tonic depolarization and frequency which outlasted the sensory input. Such recruitment could occur on both sides after local sensory stimulation to only one region or one side of the model. We conclude that these computer simulations support the hypothesis that premotor interneuron drop-out and recruitment is one mechanism which can control frequency in a locomotor central pattern generator.

Transmission in a locomotor-related group Ib pathway from hindlimb extensor muscles in the cat.

It has been previously shown that phasic stimulation of group I afferents from ankle and knee extensor muscles may entrain and/or reset the intrinsic locomotor rhythm; these afferents are thus acting on motoneurones through the spinal rhythm generators. It was also concluded that the major part of these effects originates from Golgi tendon organ Ib afferents. Transmission in this pathway to lumbar motoneurones has now been investigated during fictive locomotion in spinal cats injected with nialamide and L-DOPA, and in decerebrate cats with stimulation of the mesencephalic locomotor region. In spinal cats injected with nialamide and L-DOPA, it was possible to evoke long-latency, long-lasting reflexes upon stimulation of high threshold afferents before spontaneous fictive locomotion commenced. During that period, stimulation of ankle and knee extensor group I afferents evoked oligosynaptic excitation of extensor motoneurones, rather than the "classical" Ib inhibition. Furthermore, a premotoneuronal convergence (spatial facilitation) between this group I excitation and the crossed extensor reflex was established. During fictive locomotion, in both preparations, the transmissions in these groups I pathway was phasically modulated within the step cycle. During the flexor phase, the group I input cut the depolarised (active) phase in flexor motoneurones and evoked EPSPs in extensor motoneurones; during the extensor phase the group I input evoked smaller EPSPs in extensor motoneurones and had virtually no effect on flexor motoneurones. The above results suggest that the group I input from extensor muscles is transmitted through the spinal rhythm generator and more particularly, through the extensor "half-centre". The locomotor-related group I excitation had a central latency of 3.5-4.0 ms. The excitation from ankle extensors to ankle extensors remained after a spinal transection at the caudal part of L6 segment; the interneurones must therefore be located in the L7 and S1 spinal segments. Candidate interneurones for mediating these actions were recorded extracellularly in lamina VII of the 7th lumbar segment. Responses to different peripheral nerve stimulation (high threshold afferents and group I afferents bilaterally) were in concordance with the convergence studies in motoneurones. The interneurones were rhythmically active in the appropriate phases of the fictive locomotor cycle, as predicted by their response patterns. The synaptic input to, and the projection of these candidate interneurones must be fully identified before their possible role as components of the spinal locomotor network can be evaluated.

Control of frequency during swimming in Xenopus embryos: a study on interneuronal recruitment in a spinal rhythm generator.

1. In Xenopus embryos, the frequency of natural and fictive swimming usually drops slowly as swimming continues but can increase following stimulation of the skin or dimming of the illumination. We have investigated whether such increases are associated with an increase in the number of neurones active at higher frequencies. 2. Recordings from ventral presumed motoneurones show that these were reliably active at all swimming frequencies. 3. Recordings from more dorsal presumed interneurones showed that in the majority of these firing probability decreased as a function of swimming frequency. Dye-filled microelectrodes were used to show that some of these neurones had the anatomy of known classes of excitatory and inhibitory premotor interneurones. 4. If skin stimulation is given at appropriate phases of the swimming cycle, it can lead to a transient increase in frequency. Recordings from silent premotor interneurones during such stimulation show that they can be recruited to fire during the post-stimulus frequency increases. 5. It was possible that spike failure in the interneurones could have been due to damage by the recording microelectrodes. We therefore measured the amplitudes and probability of occurrence of rhythmic 'on-cycle' IPSPs which occur in sensory interneurones and 'on-cycle' IPSPs which sometimes occur in motoneurones during fictive swimming. Both decreased in amplitude and could fail as frequency dropped, providing further evidence that the number of inhibitory interneurones firing on each cycle of swimming is a function of frequency. 6. We conclude that premotor rhythm-generating interneurones are not active on all cycles of swimming and that their probability of firing action potentials increases with swimming frequency. This suggests that swimming frequency is determined in part by the number of premotor interneurones which are active.

Modulation of swimming rhythmicity by 5-hydroxytryptamine during post-embryonic development in Xenopus laevis.

During the first 24 h of post-embryonic development in Xenopus laevis, a rapid change in the neural activity underlying swimming occurs in which the duration of ventral root discharge on each cycle increases from a single compound impulse to discrete bursts of activity. Moreover, this change in motor output progresses rostrocaudally, suggesting that it could result from the influence of a descending neural pathway upon the spinal rhythm-generating circuitry during early post-embryonic development. To begin to examine whether serotonergic neurons of brainstem raphe nuclei might have a role in this swimming development, we have studied the effects of 5-hydroxytryptamine (5HT) on fictive swimming in embryonic and larval animals. As previously demonstrated for other vertebrate locomotor rhythms, we find that bath-applied 5HT enhances the duration of motor activity on each cycle of larval fictive swimming. In addition, our results show that the sensitivity of the swimming rhythm to exogenous 5HT follows a strict rostrocaudal gradient. In young embryos (stages 32-36) 5HT does not affect the duration of ventral root impulses per cycle; by the time of hatching (stage 37/38), rostral but not caudal discharge is enhanced, and by stage 42 (24 h post-hatching) 5HT can increase motor burst durations along most of the length of the animal. These reversible changes induced by bath-applied 5HT closely resemble the normal rostrocaudal development of burst discharge during swimming in animals some 12 h older.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of fos expression by activity in the spinal rhythm generator for scratching

Fos expression was evaluated immunohistochemically in L 7-S 1 spinal segments after inducing fictive scratching in paralysed, unanaesthetized, decerebrate cats. The activity was induced by cutaneous stimulation of the pinna on one side and recorded from peripheral nerves. A cumulative duration of scratching of 60 to 90 min was effective in inducing fos expression. Most Fos-positive neurones were found in the dorsolateral part of the ventral horn and in the intermediate region of the spinal cord on the scratching side. In sham-operated animals the finding of Fos-positive neurones in these areas was very rare.

Spinal pattern generation and sensory gating mechanisms

Sensory gating mechanisms are deployed during vertebrate locomotion to ensure that adaptive and appropriate motor responses to afferent input occur during all phases of the movement cycle. Recent animal studies on the integration of cutaneous information have investigated the roles of interneurones in sensory gating. Premotor interneurones, rhythmically active during locomotion, as well as 'sensory' interneurones appear to be intimately involved in sensory gating, receiving synaptic inputs from the spinal rhythm generator to gate the flow of sensory information in the spinal cord.

Active and Passive Membrane Properties of Spinal Cord Neurons that Are Rhythmically Active during Swimming in Xenopus Embryos.

Cellular properties have been examined in ventrally located Xenopus spinal cord neurons that are rhythmically active during fictive swimming and presumed to be motoneurons. Resting potentials and input resistances of such neurons are - 75 +/- 2 mV (mean +/- standard error) and 118 +/- 17 M ohm respectively. Most cells fire a single impulse, 0.5 to 2.0 ms in duration and 48.5 +/- 1.8 mV in amplitude, in response to a depolarizing current step. A minority fire several spikes of diminishing amplitude to more strongly depolarizing current. Cells held above spike, threshold fire on rebound from brief hyperpolarizing pulses. Spikes are blocked by 0.1 to 1.0 microM tetrodotoxin (TTX) and are therefore Na+-dependent. Current/voltage (I/V) plots to injected current are approximately linear near the resting potential but become non-linear at more depolarized levels. Cells recorded in TTX with CsCI-filled microelectrodes show a linearized I/V plot at depolarized membrane potentials suggesting the normal presence of a voltage-dependent K+ conductance activated at relatively depolarized levels. Most cells recorded in this way but without TTX fire long trains of spikes of near constant amplitude, pointing to a role of the K+ conductance in limiting firing in normal cells. Spike blockage with TTX reveals, in some cells, a transient depolarizing Cd2+-sensitive and therefore presumably Ca2+-dependent potential that increases in amplitude with depolarization. Cells in TTX, Cd2+, and strychnine, and recorded with CsCI-filled microelectrodes to block active conductances respond to hyperpolarizing current steps with a two component exponential response. The cell time constant (tau0) obtained from the longer of these by exponential peeling is relatively long (mean 15.7 ms). These findings contribute to an increased understanding of the cellular properties involved in spinal rhythm generation in this simple vertebrate.

Efferent activity during fictitious scratch reflex in the cat.

Efferent activity during fictitious scratch reflex in the cat.T G Deliagina, G N Orlovsky, and C PerretT G Deliagina, G N Orlovsky, and C PerretPublished Online:01 Apr 1981https://doi.org/10.1152/jn.1981.45.4.595MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCentral pattern generators in the turtle spinal cord: selection among the forms of motor behaviorsPaul S. G. Stein1 February 2018 | Journal of Neurophysiology, Vol. 119, No. 2Activity of the Motor Cortex During ScratchingMikhail G. Sirota, Galina A. Pavlova, and Irina N. Beloozerova1 February 2006 | Journal of Neurophysiology, Vol. 95, No. 2Deletions of Rhythmic Motoneuron Activity During Fictive Locomotion and Scratch Provide Clues to the Organization of the Mammalian Central Pattern GeneratorMyriam Lafreniere-Roula, and David A. McCrea1 August 2005 | Journal of Neurophysiology, Vol. 94, No. 2Muscle Synergies Encoded Within the Spinal Cord: Evidence From Focal Intraspinal NMDA Iontophoresis in the FrogPhilippe Saltiel, Kuno Wyler-Duda, Andrea D'Avella, Matthew C. Tresch, and Emilio Bizzi1 February 2001 | Journal of Neurophysiology, Vol. 85, No. 2Modulation of Oligosynaptic Cutaneous and Muscle Afferent Reflex Pathways During Fictive Locomotion and Scratching in the CatA. M. Degtyarenko, E. S. Simon, T. Norden-Krichmar, and R. E. Burke1 January 1998 | Journal of Neurophysiology, Vol. 79, No. 1Spinal Cord Coordination of Hindlimb Movements in the Turtle: Intralimb Temporal Relationships During Scratching and SwimmingEdelle C. Field, and Paul S. G. Stein1 September 1997 | Journal of Neurophysiology, Vol. 78, No. 3Spinal Cord Coordination of Hindlimb Movements in the Turtle: Interlimb Temporal Relationships During Bilateral Scratching and SwimmingEdelle C. Field, and Paul S. G. Stein1 September 1997 | Journal of Neurophysiology, Vol. 78, No. 3Induction of fos expression by activity in the spinal rhythm generator for scratchingBrain Research, Vol. 588, No. 1Spinal sensorimotor systems and their supraspinal controlNeuroscience Research, Vol. 7, No. 4Paw-shake responses with joint immobilization: EMG changes with atypical feedbackExperimental Brain Research, Vol. 77, No. 2The distal hindlimb musculature of the catExperimental Brain Research, Vol. 58, No. 3In vitro motor program for the rostral scratch reflex generated by the turtle spinal cordBrain Research, Vol. 266, No. 1Activity of motoneurons during fictitious scratch reflex in the catBrain Research, Vol. 193, No. 2Activity of Ia inhibitory interneurons during fictitious scratch reflex in the catBrain Research, Vol. 193, No. 2 More from this issue > Volume 45Issue 4April 1981Pages 595-604 https://doi.org/10.1152/jn.1981.45.4.595PubMed7229672History Published online 1 April 1981 Published in print 1 April 1981 Metrics