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Medioventral medulla-induced locomotion.

Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA.

Animals↗

Dopamine in the lateral hypothalamus may be involved in the inhibition of locomotion related to food and water seeking.

Experiments were conducted in male rats to assess the motor effects of bilateral intraperifornical microinjections of sulpiride, dopamine (DA) and other drugs. Sulpiride increased locomotion of the animals in all the experiments reported here. DA (10 micrograms) administered 5 minutes before sulpiride (8 micrograms) reduced the motor stimulant effect of the neuroleptic from 1601.3 +/- 337.6 to 742.5 +/- 180.4 counts/30 min. SCH 23390 (15 micrograms), haloperidol (2.5 micrograms) and atropine (18 micrograms) did not modify the locomotion level of animals acclimated to the actimeters. After carbachol (5 micrograms) the animals attained a level of hyperactivity (1459.5 +/- 146.5 counts/30 min) similar to that induced by sulpiride (1595.7 +/- 365.7 counts/30 min) in the same experiment. In other experiments DA (10 micrograms) administered 30 min before sulpiride again blocked the effect of 8 micrograms of sulpiride, and reduced the initial hyperactivity of food- and water-deprived animals previously familiarized with the actimeters (922.4 +/- 49.38 counts/15 min under saline, vs. 544 +/- 29 counts/15 min under DA). The same DA dose did not modify the initial spontaneous activity of nonfamiliarized nonfood-deprived rats (508.9 +/- 96.1 after saline vs. 520.9 +/- 47.1 after DA). These results suggest the presence of cells in the lateral hypothalamus involved in the control of locomotion. These experiments also suggest that locomotion triggered by the LH may be exploratory behavior essential to the search for water and food. As a corollary, DA in the LH appears to be involved not only in the inhibition of feeding and drinking but also in the inhibition of exploratory and food- and water-directed locomotion.

Animals↗

Computer-driven automatic identification of locomotion states in Caenorhabditis elegans.

We developed a computer-driven tracking system for the automated analysis of the locomotion of Caenorhabditis elegans. The algorithm for the identification of locomotion states on agar plates (forward movement, backward movement, rest, and curl) includes the identification of the worm's head and tail. The head and tail are first assigned, by using three criteria, based on time-sequential binary images of the worm, and the determination is made based on the majority of the three criteria. By using the majority of the criteria, the robustness was improved. The system allowed us to identify locomotion states and to reconstruct the path of a worm using more than 1h data. Based on 5-min image sequences from a total of 230 individual wild-type worms and 22 mutants, the average error of identification of the head/tail for all strains was 0.20%. The system was used to analyze 70 min of locomotion for wild-type and two mutant strains after a worm was transferred from a seeded plate to a bacteria-free assay plate. The error of identifying the state was less than 1%, which is sufficiently accurate for locomotion studies.

Algorithms↗

Conservation rules, their breakdown, and optimality in Caenorhabditis sinusoidal locomotion.

Undulatory locomotion is common to nematodes as well as to limbless vertebrates, but its control is not understood in spite of the identification of hundred of genes involved in Caenorhabditis elegans locomotion. To reveal the mechanisms of nematode undulatory locomotion, we quantitatively analysed the movement of C. elegans with genetic perturbations to neurons, muscles, and skeleton (cuticle). We also compared locomotion of different Caenorhabditis species. We constructed a theoretical model that combines mechanics and biophysics, and that is constrained by the observations of propulsion and muscular velocities, as well as wavelength and amplitude of undulations. We find that normalized wavelength is a conserved quantity among wild-type C. elegans individuals, across mutants, and across different species. The velocity of forward propulsion scales linearly with the velocity of the muscular wave and the corresponding slope is also a conserved quantity and almost optimal; the exceptions are in some mutants affecting cuticle structure. In theoretical terms, the optimality of the slope is equivalent to the exact balance between muscular and visco-elastic body reaction bending moments. We find that the amplitude and frequency of undulations are inversely correlated and provide a theoretical explanation for this fact. These experimental results are valid both for young adults and for all larval stages of wild-type C. elegans. In particular, during development, the amplitude scales linearly with the wavelength, consistent with our theory. We also investigated the influence of substrate firmness on motion parameters, and found that it does not affect the above invariants. In general, our biomechanical model can explain the observed robustness of the mechanisms controlling nematode undulatory locomotion.

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Intrathecal application of cyproheptadine impairs locomotion in intact rats.

In intact adult rats, cyproheptadine, a 5-HT2 antagonist, administered intrathecally at the midlumbar segments was found to impair hindlimb locomotor movements during overground locomotion. These effects were dose-dependent; they varied from transient complete hindlimb paraplegia seen at doses of 300 microg/20 microl, to short-lasting trunk instability at doses of 100 microg/20 microl. After the return of overground locomotion, transient abduction of one of the hindlimbs was observed in some animals. These findings demonstrate that the blockade of 5-HT2 receptors affects locomotion in intact rats. Our results provide support for the hypothesis of serotonergic involvement in rat locomotion, which, so far, has been based mainly on the effects of 5-HT2 agonists on the recovery of locomotion in spinal rats.

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Modulation of motor patterns by sensory feedback during earthworm locomotion.

Role of sensory feedback to motor pattern activity concerning locomotion in the earthworm, Eisenia fetida, was investigated. We have previously reported that bath application of octopamine induces fictive locomotion in the earthworm. In this study, we have examined the role of sensory feedback during fictive locomotion by analyzing electrical activities from the cut end and intact first lateral nerves of the ventral nerve cord (VNC). From the cut end recordings, motor activity associated with fictive locomotion was measured. A mixture of sensory and motor activities was measured from the intact first lateral nerve using en passant recordings, and sensory activity was separated by subtraction of the cut end recording (mainly motor activities) from the intact first lateral nerve recording. We estimated the effect of sensory feedback from the earthworm body wall by comparing recordings that made when the preparation was in-contact with a substrate or suspended above it. Motor pattern activities and the coefficient of variation for inter-spike-interval of motor outputs were increased under suspended conditions during circular muscle contraction. These results indicate that sensory feedback modulates the pattern of motor activity in the earthworm during locomotion.

Action Potentials↗

The spinal 5-HT system contributes to the generation of fictive locomotion in lamprey.

Activation of NMDA receptors evokes sustained fictive locomotion in the isolated spinal cord of the sea lamprey Petromyzon marinus (P. marinus), but in the river lamprey Lampetra fluviatilis (L. fluviatilis) the ventral root activity is often irregular. A previous study showed that the number of 5-HT immunoreactive fibres, neurones and varicosities are much lower in the spinal cord of L. fluviatilis than in P. marinus. To further analyse the underlying mechanisms, the present study investigated the role of the 5-HT system in stabilising fictive locomotion. In P. marinus a blockade of 5-HT1A receptors by spiperone reversibly increased the frequency and the coefficient of variation. This implies that there is an endogenous release of 5-HT during fictive locomotion that is important for the generation of locomotor activity. In L. fluviatilis bath applied NMDA or D-glutamate evoked in most cases irregular activity. An addition of 5-HT (0.5-2 microM) rapidly stabilised the burst generation and led to a sustained fictive locomotion. In a split-bath configuration, NMDA administered to the rostral part of the spinal cord in P. marinus evoked fictive locomotion in both the rostral part and the first few segments of the caudal part. When spiperone was added to the caudal part, the burst activity changed into tonic activity within 10 min. Taken together, these results indicate that activity in the intrinsic 5-HT system in the lamprey spinal locomotor network contributes significantly to the rhythm generation. The quantitative differences with regard to the 5-HT plexus between P. marinus and L. fluviatilis may account for the observed discrepancy between the two species.

Animals↗

Correlations between neurograms and locomotor drive potentials in motoneurons during fictive locomotion: implications for the organization of locomotor commands.

The patterns of correlation found between motoneuron pools during fictive locomotion are the same whether the coherence functions used to detect the correlations are determined using pairs of rectified ENGs or motoneuron LDPs and rectified ENGs. This finding suggests that the higher frequencies in rectified ENGs (and, perhaps, EMGs) contain information about the synaptic input to motoneurons. Nevertheless, differences between the coherence functions of rectified ENG pairs and those of LDPs and rectified ENGs suggests that this information is distorted by harmonics introduced by rectification. The activities of many motoneuron pools are correlated during the flexor or extensor phase of fictive locomotion, indicating that they receive common synaptic input from branched presynaptic axons or from pools of interneurons whose activities are synchronized. Similar findings were reported by Bayev (1978), based on temporal correlations. Our results indicate that the investigated motor nuclei, which innervate muscles with actions at the hip, knee and ankle, are subject to a set of common locomotor commands. These commands are also received by inhibitory interneurons that project to the motor nuclei of antagonists, as indicated by the correlations between the hyperpolarizing phase of LDPs and activity in the rectified ENGs of antagonists. This last result is consistent with a modular organization for the spinal locomotor generator, in which one set of interneurons drives a motor pool and the inhibitory interneurons that project to the motor pool's antagonist (Jordan, 1991). However, these results also suggest that the spinal modules for locomotion may not be separable into independent unit-burst generators that produce commands for control of each joint as Grillner (1981) has suggested. Our results are more consistent with a model in which a generator distributes flexor and extensor commands to many motor pools (like the half-center model) with as yet unidentified spinal mechanisms that determine differences in the initiation and termination of activity of individual motor nuclei. Alternatively, the correlations between motor pools that we have observed could be explained by spinal mechanisms that synchronize the activity of unit-burst type generators. Despite the distribution of common locomotor commands to many functionally diverse motor nuclei, the spinal locomotor pattern generator is differentiated to the extent that some motor nuclei, like EDL and FDL, receive separate locomotor commands. This conclusion is consistent with other observations. EDL and FDL display distinctive, individualized patterns of locomotor activity that may vary in a facultative manner or in different forms of locomotion (O'Donovan et al., 1980; Trank et al., 1996). A recent study has shown that during fictive locomotion EDL and FDL motoneurons receive input from different sets of last-order interneurons than those which project to other motor pools (Degtyarenko et al., 1998). These results suggest that spinal locomotor generators are differentiated for the individualized control of some digit muscles, like FDL and EDL.

Animals↗

The effects of limbic lesions on locomotion and stereotypy elicited by dopamine agonists in the rat.

The purpose of this experiment was to investigate the functional contributions of various limbic structures to locomotion and stereotypy induced by dopaminergic drugs. Female rats were randomly assigned to one of 5 groups (n = 10-14 rats/group) that received either a lesion of the hippocampus (colchicine + kainic acid), basolateral amygdala (quinolinic acid), frontal cortex (aspiration), nucleus accumbens (ibotenic acid), or served as unoperated controls. Beginning at least 2 weeks following surgery locomotion (measured as photocell beam breaks) elicited by D-amphetamine (0.0, 0.32, 1.0 and 3.2 mg/kg), SKF 82958 (0.0, 0.04, 0.08 and 0.16 mg/kg) or quinpirole (0.0, 0.25, 0.1 and 0.5 mg/kg) was determined. In agreement with previous results rats with hippocampal lesions were hyperactive in response to amphetamine. In comparison to these changes in drug-induced locomotion, lesions of the basolateral amygdala, and frontal cortex had only minor effects on drug-induced locomotion. Lesions of the nucleus accumbens produced consistent hyperactivity that was suppressed by doses of amphetamine or quinpirole that elicited behavioral stereotypy. These results provide evidence suggesting that, in comparison to other limbic structures that have substantial inputs to the nucleus accumbens, the hippocampus play a relatively prominent role in the modulation of drug-induced locomotion.

Amphetamine↗

Complete locomotor recovery following corticospinal tract lesions: measurement of ground reaction forces during overground locomotion in rats.

The corticospinal tract is a prominent descending pathway in rodents which is thought to be involved in motor control. The purpose of this study was to investigate whether the lesions of the corticospinal tract affected overground locomotion in rats using a method of assessment which is relatively novel in this field, the evaluation of ground reaction forces. Ground reaction forces, i.e. the forces acting through the limbs on the ground, are a non-invasive, sensitive and quantitative method with which to assess gait compensation and the function of individual limbs during locomotion. We compared the three-dimensional ground reaction forces produced by locomoting rats with a unilateral corticospinal tract transection to those of control rats. Corticospinal-lesioned animals showed transient locomotor deficits 24-48 h after the lesion which quickly recovered to normal symmetrical locomotion. The initial locomotor deficits consisted of an asymmetric gait during which abnormal braking forces were produced during the dual contact time of the forelimb contralateral to the lesion (the impaired forelimb) and the ipsilateral (unimpaired) hindlimb. Normal forces were produced during the dual contact time of the ipsilateral (unimpaired) forelimb and the contralateral (impaired) hindlimb. The presence of the initial deficits may be a result of inflammation in the area of the lesion or may reflect a loss of normal locomotor contribution of the corticospinal tract. If the latter, the nature of the locomotor deficit suggests that (a) the forelimb may be more influenced by corticospinal lesions than is the hindlimb and/or (b) that the asymmetric gait produced is a general compensatory response to unilateral CNS injury in a quadruped. Complete recovery from corticospinal tract transection provides unequivocal evidence that input from the corticospinal tract is not essential for normal overground locomotion in the rat.

Animals↗

Identification of two types of synaptic activity in the earthworm nervous system during locomotion.

In the ventral nervous system of the earthworm, a central pattern generator and motor neurons are activated during locomotion. We have previously reported that bath application of octopamine (OA) induces fictive locomotion in the earthworm, and the burst frequency of electrical activity from the first lateral nerves increases with OA concentration. However, there are no reports concerning locomotor neural networks in the earthworm. To identify neural networks involved in fictive locomotion, we optically monitored activity-dependent fluorescent staining in the earthworm ventral nerve cord (VNC) with a styryl dye, N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. OA induces FM1-43 fluorescence in a dose-dependent manner, with bright fluorescent spots of 3-10 microm in diameter observed to be localized around specified neurons in the segmental ganglion of the VNC. We compared OA dose-response curves for FM1-43 fluorescence with the bursting frequency for fictive locomotion, and found that two types of curves could be identified: one fluorescence response shows a similar dose-dependency to that of the burst frequency, while another response has a higher sensitivity to OA. From these results, we suggest that OA acts as one of the neuromodulators for the earthworm locomotion. This is the first attempt to record motor and inter-neuronal activities simultaneously in a locomotor network in the earthworm.

Action Potentials↗

Is the cuneiform nucleus a critical component of the mesencephalic locomotor region? An examination of the effects of excitotoxic lesions of the cuneiform nucleus on spontaneous and nucleus accumbens induced locomotion.

The cuneiform nucleus and the pedunculopontine tegmental nucleus have both been suggested as possible sites for the mesencephalic locomotor region (MLR), an area from which controlled stepping on a treadmill can be elicited following electrical or chemical stimulation in a decerebrate animal. It has been shown that excitotoxic lesions of the pedunculopontine tegmental nucleus impair neither spontaneous locomotion nor locomotion induced by stimulation of the nucleus accumbens. Excitotoxic lesions of the cuneiform nucleus have not previously been investigated. Rats received either bilateral ibotenate or sham lesions of the cuneiform nucleus combined with bilateral implantation of guide cannulae aimed at the nucleus accumbens. On recovery from surgery spontaneous locomotion was tested, followed by accumbens-stimulated locomotion. For nucleus accumbens stimulation, each rat received bilateral microinjection of each of three doses of d-amphetamine (10.0, 20.0 and 30.0 micrograms) and a vehicle only injection. Locomotor activity was recorded following the injection. In comparison to the sham-lesioned group, the ibotenate-lesioned group showed no differences in either spontaneous or amphetamine-induced locomotor activity. These results suggest that, like the pedunculopontine tegmental nucleus, the cuneiform nucleus is not involved in the direct mediation of spontaneous or accumbens-induced locomotion, and thus is very unlikely to be the anatomical substrate of the MLR. The role of the cuneiform nucleus in other types of behavioural control is discussed.

Amphetamine↗

Gait analysis during treadmill and overground locomotion in children and adults.

Gait analysis on the treadmill and in the overground condition is used both in scientific approaches for investigating the neuronal organisation and ontogenetic development of locomotion and in a variety of clinical applications. We investigated the differences between overground and treadmill locomotion (at identical gait velocity) in 12 adults and 14 children (6-7 years old). During treadmill locomotion the step frequency increased by 7% in adults and 10% in children compared to overground walking, whereas the stride length and the stance phase of the walking cycle decreased. The swing phase, however, increased significantly by 5% in adults and remained unchanged in children. Balance-related gait parameters such as the step width and foot rotation angles increased during treadmill locomotion. The reduction of the step length was found to be stable after 10 min of treadmill walking in most subjects. With regard to the shifted phases of the walking cycle and the changed balance related gait parameters in the treadmill condition, we assume a different modulation of the central pattern generator in treadmill walking, due to a changed afferent input. Regarding the pronounced differences between overground and treadmill walking in children, it is discussed whether the systems generating and integrating different modulations of locomotion into a stable movement pattern have reached full capacity in 6-7 year old children.

Adult↗

Intermittent locomotion increases endurance in a gecko.

Nocturnal geckos can actively forage at low temperatures. A low minimum cost of locomotion allows greater sustainable speeds by partially offsetting the decrease in maximal oxygen consumption (VO2max) associated with low nocturnal temperatures. The nocturnality hypothesis (Autumn et al. 1997) proposes that the reduced cost of continuous locomotion is a shared, derived characteristic that increases the capacity to sustain locomotion at low temperatures. Yet many lizards move intermittently at speeds exceeding those that elicit VO2max. We exercised the frog-eyed gecko, Teratoscincus przewalskii, continuously and intermittently on a treadmill. At an exercise speed of 0.90 km h-1 (270% maximum aerobic speed), lizards alternating a 15-s exercise period with a 30-s pause period exhibited a 1.7-fold increase in distance capacity (total distance traveled before fatigue) compared with lizards exercised continuously at the same average speed (0.30 km h-1). The average aerobic cost of intermittent exercise was not significantly different from VO2max. Locomoting intermittently could augment the increase in endurance resulting from the low minimum cost of continuous locomotion in nocturnal geckos. Intermittent behavior could increase the endurance of lizard movement in general.

Animals↗

Head movements during locomotion in a gibbon and Japanese macaques.

Kinematic analysis of head and body movements during locomotion in Macaca fuscata and Hylobates lar revealed that coordinated head rotation and translation that have been reported to play an important role in stabilizing gaze during locomotion for humans are also observed in non-human primates. The fact that well-coordinated head movements were observed in two species, and during both bipedal and quadrupedal walking, suggests that the head orientation during locomotion is well regulated in the manner of top-down control over the species and modes of locomotion. The result validates the monkey model and enables us to explore the underlying mechanisms for gaze, head, and postural control during locomotion.

Animals↗

Modulation of spinal excitability during observation of bipedal locomotion.

This study investigated whether a mirror mechanism exists for bipedal locomotion. We employed the soleus (plantar flexor) Hoffman reflex to investigate corticospinal excitability at the spinal level during observation of bipedal locomotion. The differential amplitude modulation of the left soleus Hoffman reflex during observation of bipedal heel-stepping (plantar dorsiflexion) (324+/-53 microV), standing still (383+/-60 microV), and bipedal toe-stepping (plantar flexion) (419+/-53 microV) reached significance (P < 0.05). The observation of bipedal toe-stepping produced a greater increase in spinal excitability than the observation of bipedal heel-stepping. These findings support the suggestion that there is a mirror mechanism for bipedal locomotion and they demonstrate that spinal excitability for observation of bipedal locomotion mirrors that for execution of bipedal locomotion.

Adult↗

Neurotensin antagonist acutely and robustly attenuates locomotion that accompanies stimulation of a neurotensin-containing pathway from rostrobasal forebrain to the ventral tegmental area.

Neurotensin exerts complex effects on the mesolimbic dopamine system that alter motivation and contribute to neuroadaptations associated with psychostimulant drug administration. Activation of abundant neurotensin receptors in the ventral tegmental area (VTA) enhances dopamine neuron activity and associated release of dopamine in the nucleus accumbens (Acb) and cortex. In view of recent anatomical studies demonstrating that 70% of all neurotensin-containing neurons projecting to the VTA occupy the lateral preoptic area-rostral lateral hypothalamus (LPH) and lateral part of the medial preoptic area (MPOA), the present study examined functionality in the LPH-MPOA neurotensinergic pathway in the rat. Disinhibition (resulting ultimately in stimulation-like effects) of LPH-MPOA neurons with microinjected bicuculline (50 or 100 ng in 0.25 microL) produced locomotor activation that was considerably attenuated by systemic administration of the neurotensin antagonist SR 142948 A (0.03 and 0.1 mg/kg). In contrast, locomotion elicited in this manner was completely blocked by SR 142948 A infused directly into the VTA (5.0 and 15.0 ng in 0.25 microL). Baseline locomotion was unaffected by systemic or intra-VTA administration of SR 142948 A and LPH-MPOA-elicited locomotion was unaffected by infusion of SR 142948 A into the substantia nigra pars compacta and sites rostral and dorsal to the VTA. Locomotion was not elicited by infusions of bicuculline into the lateral hypothalamus at sites caudal to the LPH-MPOA, where neurotensin neurons projecting to the VTA are fewer. The results demonstrate the capacity of a neurotensin-containing pathway from LPH-MPOA to VTA to modulate locomotion. This pathway may be important in linking hippocampal and mesolimbic mechanisms in normal behaviour and drug addiction.

Animals↗

Spinal circuitry of sensorimotor control of locomotion.

During locomotion many segmental hindlimb reflex pathways serve not only to regulate the excitability of local groups of motoneurones, but also to control the basic operation of the central pattern-generating circuitry responsible for locomotion. This is accomplished through a reorganization of reflexes that includes the suppression of reflex pathways operating at rest and the recruitment during locomotion of previously unrecognized types of spinal interneurones. In addition presynaptic inhibition of transmission from segmental afferents serves to regulate the gain of segmental reflexes and may contribute to the selection of particular reflex pathways during locomotion. The fictive locomotion preparation in adult decerebrate cats has proved to be an important tool in understanding reflex pathway reorganization. Further identification of the spinal interneurones involved in locomotor-dependent reflexes will contribute to our understanding not only of reflex pathway organization but also of the organization of the mammalian central pattern generator.

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