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PubMed2000

Spinal cholinergic neurons activated during locomotion: localization and electrophysiological characterization.

The objective of the present study was to determine the location of the cholinergic neurons activated in the spinal cord of decerebrate cats during fictive locomotion. Locomotion was induced by stimulation of the mesencephalic locomotor region (MLR). After bouts of locomotion during a 7-9 h period, the animals were perfused and the L(3)-S(1) spinal cord segments removed. Cats in the control group were subjected to the same surgical procedures but no locomotor task. The tissues were sectioned and then stained by immunohistochemical methods for detection of the c-fos protein and choline acetyltransferase (ChAT) enzyme. The resultant c-fos labeling in the lumbar spinal cord was similar to that induced by fictive locomotion in the cat. ChAT-positive cells also clearly exhibited fictive locomotion induced c-fos labeling. Double labeling with c-fos and ChAT was observed in cells within ventral lamina VII, VIII, and possibly IX. Most of them were concentrated in the medial portion of lamina VII close to lamina X, similar in location to the partition and central canal cells found by Barber and collaborators. The number of ChAT and c-fos-labeled neurons was increased following fictive locomotion and was greatest in the intermediate gray, compared with dorsal and ventral regions. The results are consistent with the suggestion that cholinergic interneurons in the lumbar spinal cord are involved in the production of fictive locomotion. Cells in the regions positive for double-labeled cells were targeted for electrophysiological study during locomotion, intracellular filling, and subsequent processing for ChAT immunohistochemistry. Three cells identified in this way were vigorously active during locomotion in phase with ipsilateral extension, and they projected to the contralateral side of the spinal cord. Thus a new population of spinal cord cells can be defined: cholinergic partition cells with commissural projections that are active during the extension phase of locomotion.

Animals↗

PubMed2005

Coordination of locomotion with voluntary movements in humans.

Muscle activity occurring during human locomotion can be accounted for by five basic temporal activation patterns in a variety of locomotion conditions. Here, we examined how these activation patterns interact with muscle activity required for a voluntary movement. Subjects produced a voluntary movement during locomotion, and we examined the resulting kinematics, kinetics, and EMG activity in 16-31 ipsilateral limb and trunk muscles during the tasks. There were four voluntary tasks added to overground walking (approximately 5 km/h) in which subjects kicked a ball, stepped over an obstacle, or reached down and grasped an object on the floor (weight support on either the right or the left foot). Statistical analyses of EMG waveforms showed that the five basic locomotion patterns were invariantly present in each task, although they could be differently weighted across muscles, suggesting a characteristic locomotion timing of muscle activations. We also observed a separate activation that was timed to the voluntary task. The coordination of locomotion with the voluntary task was accomplished by combining activation timings that were associated separately with the voluntary task and locomotion. Activation associated with the voluntary tasks was either synchronous with the timing for locomotion or had additional activations not represented in the basic locomotion timing. We propose that this superposition of an invariant locomotion timing pattern with a voluntary activation timing may be consistent with the proposal suggesting that compound movements are produced through a superposition of motor programs.

Acceleration↗

PubMed2006

Risk factors for reduced locomotion in dairy cattle on nineteen farms in The Netherlands.

A 3-point locomotion scoring system was used that incorporated the position of the back of cows while standing and when walking to investigate risk factors for elevated locomotion scores of 1,450 dairy cows on 19 farms in The Netherlands. Each of the farms was visited twice in an 18-mo period from February 2003 to July 2004. At each visit, all milking and dry cows were scored for locomotion by a single observer. Two multivariable regression models were constructed to identify factors associated with elevated mean locomotion score (increased abnormality) and the percentage of cows with the highest score (score 3). Risk factors for increased locomotion score were having a hoof-trimming stall with foot-lifting apparatus compared with not having such apparatus (increase in locomotion score = 0.15), presence of a footbath at the parlor exit or other site compared with not having a footbath on the farm (increase in locomotion score = 0.17 and 0.19, respectively), not providing supplemental vitamins and minerals to lactating cows compared with supplementing animals (increase in locomotion score = 0.17) and feeding corn silage to heifers compared with not doing so (increase in locomotion score = 0.10). The results provide a framework for hypotheses for future investigations of risk factors for high locomotion scores.

Analysis of Variance↗

PubMed1991

Presynaptic dopaminergic neurotransmission mediates amphetamine-induced unconditioned but not amphetamine-conditioned locomotion and defecation in the rat.

A series of experiments were conducted to investigate the role of presynaptic dopamine (DA) and noradrenaline (NA) neurotransmission in stimulant-unconditioned and conditioned locomotion and defecation. (+)-Amphetamine (AMP, 1.5 mg/kg, s.c.) increased both locomotion and defecation in rats, and both of these effects were conditioned to environmental stimuli. Some groups of rats were treated with DSP4 (50 mg/kg, i.p.), a selective, long-lasting NA neurotoxin, given 7 days prior to conditioning with AMP. This treatment depleted forebrain NA to between 1% and 54% of control levels, depending on the brain region, but did not attenuate either AMP-unconditioned or conditioned locomotion. These results indicate that NA does not mediate either AMP unconditioned or conditioned locomotion. alpha-Methyl-para-tyrosine methyl ester (alpha MPT, 25-50 mg/kg, s.c.), a selective inhibitor of catecholamine synthesis given during conditioning with AMP, attenuated unconditioned AMP-induced locomotion and defecation but did not influence AMP-conditioned locomotion and defecation. Thus, alpha MPT blocked AMP-induced unconditioned locomotion, supporting the hypothesis that the locomotor and defecation stimulant effects of AMP are mediated by DA release. In spite of the attenuation of the direct effects of AMP, alpha MPT did not attenuate AMP-conditioned locomotion or defecation. It is concluded that AMP-induced release of dopamine is responsible for the unconditioned behavioral effects of amphetamine but not for the conditioning of amphetamine-induced locomotion and defecation.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1987

Integration of posture and locomotion in acute decerebrate cats and in awake, freely moving cats.

For the past 10 years, our group has been engaged in the study of posture and locomotion in decerebrate cats and in freely moving awake cats. Our initial objective was to analyse the neuronal mechanisms of locomotion from a viewpoint of "postural control". Therefore, in this review, I have focussed my attention on two major control aspects of the brain stem; one related to the interaction of posture and locomotion; and the other to initiation of locomotion. It is apparent that elucidation of the second aspect is feasible. In Fig. 15, I have summarized all the neuronal structures that have been functionally identified as being actively involved in the regulation of posture and locomotion. Obviously, contribution of the cerebello-cerebral pathways and the basal ganglia to both the postural and to the locomotor control cannot be elucidated in decerebrate preparations (Fig. 15A). These contributions can, to a certain degree, be elucidated in intact awake cats (Fig. 15B). Although it is difficult to directly compare the results obtained in the decerebrate cats with those obtained in intact cats, it has been encouraging that the selective activation of certain neuronal structures within the brain stem allowed us to evoke comparable postural and locomotor changes in both groups of preparations. It can be expected that the knowledge obtained from studies of the cerebello-cerebral pathways and of the basal ganglia, together with those that can be further obtained from studies of the brain stem, should result in the elucidation of the two major control aspects of the brain stem described above. In this sense, both the models of the decerebrate locomotor preparation and the freely moving, awake cat seem to provide an unique opportunity to study the nature and the sources of command signals that set the postural and the locomotor synergies into a single functional synergy, and even to approach elucidation of the intriguing question as to how and where volitional control signals for initiating and/or halting locomotion are organized. More than 70 years have passed since the pioneer studies by Sherrington (1906) and by Graham Brown (1911, 1914) on postural control and on locomotion, as exemplified by "decerebrate reflex standing, and stepping" and the "central rhythmic generator" relating to locomotion. Based on these discoveries, Shik, Severin and Orlovsky (1966) have made a splendid breakthrough in a wide area of investigation relating to locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2004

Locomotion induced by non-contingent intracranial stimulation: comparison to psychomotor stimulant.

Non-contingent experimenter-applied stimulation (nEAS) to the ventral mesencephalon, unlike contingent intracranial self-stimulation (ICSS), elicits high rates of general locomotion. This locomotion may be due to the nature of the presentation of stimulation, in that nEAS is non-contingent, while ICSS depends on a specific and focused response (e.g., bar pressing). Psychomotor stimulants also elicit high amounts of general locomotion, with the locomotion attributed to increased dopamine release. Interestingly, dopamine release decreases or is absent with repeated ICSS, but not nEAS. This suggests that the locomotion elicited by nEAS may be the result of DA release similar to that observed with psychomotor stimulants. To determine the relationship between locomotion induced by nEAS and psychomotor stimulants, locomotion elicited by nEAS was directly compared to that produced by cocaine, a psychomotor stimulant and indirect DA agonist. Six groups of rats were examined: (1) DA+ group: rats were implanted with a stimulating electrode in the ventral mesencephalon and activation of DA neurons was verified during surgery by monitoring DA release in the striatum; (2) DA- group: rats were also implanted with stimulating electrodes, but the location in the ventral mesencephalon did not elicit DA release; (3) 10-mg/kg cocaine group: rats were exposed to a low dose (10 mg/kg) of cocaine; (4) 40-mg/kg cocaine group: rats were exposed to a high dose (40 mg/kg) of cocaine; (5) saline group: rats were injected with saline; and (6) naive group: rats received no treatment. The topography of behavior was assessed in all rats during four periods: a pre-treatment baseline, treatment, early post-treatment, and a late post-treatment end point. The results suggest that locomotion elicited by nEAS was stereotypic, dependent upon DA release and similar, but not identical, to psychomotor stimulant-induced locomotion.

Animals↗

PubMed2001

State-dependent hyperpolarization of voltage threshold enhances motoneurone excitability during fictive locomotion in the cat.

Experiments were conducted on decerebrate adult cats to examine the effect of brainstem-evoked fictive locomotion on the threshold voltage (Vth) at which action potentials were initiated in hindlimb motoneurones. Measurements of the voltage threshold of the first spike evoked by intracellular injection of depolarizing ramp currents or square pulses were compared during control and fictive locomotor conditions. The sample of motoneurones included flexor and extensor motoneurones, and motoneurones with low and high rheobase currents. In all 38 motoneurones examined, action potentials were initiated at more hyperpolarized membrane potentials during fictive locomotion than in control conditions (mean hyperpolarization -8.0 +/- 5.5 mV; range -1.8 to -26.6 mV). Hyperpolarization of Vth occurred immediately at the onset of fictive locomotion and recovered in seconds (typically < 60 s) following the termination of locomotor activity. The Vth of spikes occurring spontaneously without intracellular current injection was also reduced during locomotion. Superimposition of rhythmic depolarizing current pulses on current ramps in the absence of locomotion did not lower Vth to the extent seen during fictive locomotion. We suggest that Vth hyperpolarization results from an as yet undetermined neuromodulatory process operating during locomotion and is not simply the result of the oscillations in membrane potential occurring during locomotion.The hyperpolarization of Vth for action potential initiation during locomotion is a state-dependent increase in motoneurone excitability. This Vth hyperpolarization may be a fundamental process in the generation of motoneurone activity during locomotion and perhaps other motor tasks.

Action Potentials↗

PubMed2001

Comparison of the effect of intrathecal administration of clonidine and yohimbine on the locomotion of intact and spinal cats.

Several studies have shown that noradrenergic mechanisms are important for locomotion. For instance, L-dihydroxyphenylalanine (L-DOPA) can initiate "fictive" locomotion in immobilized acutely spinalized cats and alpha(2)-noradrenergic agonists, such as 2,6,-dichloro-N-2-imidazolidinylid-enebenzenamine (clonidine), can induce treadmill locomotion soon after spinalization. However, the activation of noradrenergic receptors may be not essential for the basic locomotor rhythmicity because chronic spinal cats can walk with the hindlimbs on a treadmill in the absence of noradrenergic stimulation because the descending pathways are completely severed. This suggests that locomotion, in intact and spinal conditions, is probably expressed and controlled through different neurotransmitter mechanisms. To test this hypothesis, we compared the effect of the alpha(2) agonist, clonidine, and the antagonist (16 alpha, 17 alpha)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L(3)--L(4) before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50-150 microg/100 microl) modulated the locomotor pattern slightly causing a decrease in duration of the step cycle accompanied with some variation of EMG burst amplitude and duration. In the spinal state, clonidine could trigger robust and sustained hind limb locomotion in the first week after the spinalization at a time when the cats were paraplegic. Later, after the spontaneous recovery of a stable locomotor pattern, clonidine prolonged the cycle duration, increased the amplitude and duration of flexor and extensor bursts, and augmented the foot drag at the onset of swing. In intact cats, yohimbine at high doses (800--1600 microg/100 microl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 microg/100 microl), only had slight effects such as abduction of one of the hindlimbs and the turning of the hindquarters to one side. After spinalization, yohimbine had no effect even at the largest doses. These results indicate that, in the intact state, noradrenergic mechanisms probably play an important role in the control of locomotion since blocking the receptors results in a marked disruption of walking. In the spinal state, although the receptors are still present and functional since they can be activated by clonidine, they are seemingly not critical for the spontaneous expression of spinal locomotion since their blockade by yohimbine does not impair spinal locomotion. It is postulated therefore that the expression of spinal locomotion must depend on the activation of other types of receptors, probably related to excitatory amino acids.

Adrenergic alpha-Agonists↗

PubMed1988

Locomotion produced in mesencephalic cats by injections of putative transmitter substances and antagonists into the medial reticular formation and the pontomedullary locomotor strip.

The purpose of this study was to determine the distribution of cells in the medial reticular formation (MRF) and the pontomedullary locomotor strip (PLS), which can induce locomotion when activated. Controlled microinjections of neuroactive substances (Goodchild et al., 1982) into the MRF or PLS were made in order to activate cell bodies in those areas. The ability of trigeminal receptive field stimulation to induce locomotion before and after drug infusion into the PLS was also assessed since the PLS and the spinal nucleus of the trigeminal nerve are similar in their anatomical distribution. Experiments were performed on precollicular-postmamillary decerebrate cats walking on a treadmill. Injections of glutamic acid (GA; 500 nmol) into the MRF produced locomotion that was antagonized by infusion of glutamic acid diethyl ester into the same spot. Decreases in the current threshold for locomotion produced by electrical stimulation of the MRF were observed when the MRF was infused with either GA (40-80 nmol), DL-homocysteic acid (DL-HCA; 200 nmol), or picrotoxin (PIC; 15 nmol). Injections of GA (100 nmol), DL-HCA (700 nmol), PIC (10-50 nmol), and substance P (2 nmol) into the PLS also produced locomotion. Locomotion produced by injections of PIC into the PLS was blocked by infusion of equal amounts of muscimol or GABA. Effective PLS injection sites were all confined to the trigeminal spinal nucleus or immediately ventral and medial to this in the adjacent lateral reticular formation. Trigeminal nerve peripheral field stimulation evoked locomotion after microinjection of PIC into the PLS, although this same facial stimulus was not effective prior to drug injection. We conclude that the MRF and PLS regions of the cat brain stem contain cells that produce locomotion when chemically stimulated, and we suggest that the PLS is closely related to or synonymous with the spinal nucleus of the trigeminal nerve. Furthermore, we suggest that stimulation of trigeminal afferents is analogous to stimulation of segmental afferent pathways in the production of locomotion (Sherrington, 1910; Jankowska et al., 1967; Afelt, 1970; Budakova, 1972; Grillner and Zangger, 1979).

Animals↗

PubMed2000

Redundancy of lamellipodia in locomoting Walker carcinosarcoma cells.

Locomoting metazoan cells usually form lamellipodia at the leading front and it is widely accepted that lamellipodia are required for locomotion. In this case, suppression of lamellipodia must stop locomotion. However, the experiments show that lamellipodia are redundant for locomotion of Walker carcinosarcoma cells. Low latrunculin A concentrations (10(-7) M) transform polarised locomoting cells with lamellipodia into cells without morphologically recognisable protrusions showing an increased speed of locomotion and a reduced amount of cellular F-actin. Whereas untreated cells show a fairly linear distribution of F-actin along the plasma membrane, cells lacking morphologically recognizable protrusions at the front show modifications at the front consisting in an irregular distribution of F-actin with formation of small or large patches of F-actin alternating with small or large gaps in the F-actin layer. This is associated with a reduced resistance to deformation pressure at the front of the cell. High concentrations of latrunculin A (>10(-7) M) compromising contraction at the rear stop locomotion, suggesting that cortical contraction is important for locomotion to occur in these cells. The results are consistent with the view that actin polymerization is important for formation of lamellipodia but they are not compatible with the view that lamellipodia are essential for locomotion of Walker carcinosarcoma cells. A unifying hypothesis for the formation of different types of protrusions is proposed.

Actins↗

PubMed2003

Locomotor inhibition induced by procaine injections into the nucleus accumbens core, but not the medial ventral striatum: implication for cocaine-induced locomotion.

We examined whether injections of the local anesthesia procaine into the nucleus accumbens core disrupts locomotion more readily than those into the medial ventral striatum. Spontaneous locomotion decreased during the first 10 min immediately following injections of procaine into the core. When procaine was co-administered with d-amphetamine into the core, the injections also decreased amphetamine-induced locomotion during the initial 10 min. On the other hand, no detectable effect on spontaneous or amphetamine-induced locomotion was found when procaine was injected into the medial ventral striatum, including the medial shell and medial olfactory tubercle. We replicated our recent finding that cocaine injections into the core induced delayed, modest locomotion, while cocaine injections into the medial ventral striatum induced immediate, vigorous locomotion. Injections of amphetamine into the core induced as equally vigorous locomotion as that of the medial ventral striatum. These results show that the neurons of the core involved in locomotion are more vulnerable to local anesthesia than the neurons of the medial ventral striatum. In other words, cocaine at the doses inducing vigorous locomotion in the medial ventral striatum induces local anesthesia when applied to the core.

Anesthetics, Local↗

PubMed2002

Effects of intrathecal glutamatergic drugs on locomotion I. NMDA in short-term spinal cats.

Excitatory amino acids (EAA) have been reported to induce fictive locomotion in different in vitro and in vivo preparations in a variety of species through their actions on both N-methyl-D-aspartate (NMDA), and non-NMDA receptors. NMDA-induced intrinsic membrane properties such as intrinsic motoneuronal membrane oscillations and plateau potentials have been suggested to play a role in the generation of locomotion. There is, however, no information on the ability of NMDA in triggering spinal locomotion in awake behaving animals. Because most of the previous work on the induction of locomotion has concentrated on monoaminergic drugs, mainly noradrenergic drugs, the aim of this study is to examine the potential of NMDA in initiating locomotion in chronic spinal cats within the first week after spinalization. Five cats chronically implanted with an intrathecal cannula and electromyographic (EMG) electrodes were used. EMG activity synchronized to video images of the hindlimbs were recorded. The results show that during the early posttransection period (within the 1st week postspinalization), NMDA did not trigger robust locomotion as did noradrenergic drugs. The predominant effects of NMDA were a general hyperexcitability reflected by fast tremor, toe fanning, and an increase in small alternating hindlimb movements with no foot placement nor weight support. During the intermediate phase posttransection (6-8 days), when the cats were able to make some rudimentary steps with foot placement, NMDA significantly enhanced the locomotor performance, which lasted for 24-72 h postinjection. NMDA was also found to increase the excitability of the cutaneous reflex transmission only in early spinal cats. One possible hypothesis for the ineffectiveness of NMDA in triggering locomotion in early spinal cats could be attributed to the widespread activation of NMDA receptors on various neuronal elements involved in the transmission of afferent pathways that in turn may interfere with the expression of locomotion. The marked effects of NMDA in intermediate-spinal cats suggest that NMDA receptors play an important role in locomotion perhaps through its role on intrinsic membrane properties of neurons in shaping and amplifying spinal neuronal transmission or by augmenting the sensory afferent inputs. The long-term effects mediated by NMDA receptors have been reported in the literature and may involve mechanisms such as induction of long-term potentiation or interactions with neuropeptides. The effects of NMDA injection in intact cats and long-term chronic spinal cats will be addressed in a forthcoming companion paper.

Animals↗

PubMed1996

Efficiency of uphill locomotion in nocturnal and diurnal lizards

Nocturnal geckos can walk on level ground more economically than diurnal lizards. One hypothesis for why nocturnal geckos have a low cost of locomotion is that they can perform mechanical work during locomotion more efficiently than other lizards. To test this hypothesis, we compared the efficiency of the nocturnal gecko Coleonyx variegatus (average body mass 4.2 g) and the diurnal skink Eumeces skiltonianus (average body mass 4.8 g) when they performed vertical work during uphill locomotion. We measured the rate of oxygen consumption when each species walked on the level and up a 50 slope over a range of speeds. For Coleonyx variegatus, the energetic cost of traveling a unit distance (the minimum cost of transport, Cmin) increased from 1.5 to 2.7 ml O2 kg-1 m-1 between level and uphill locomotion. For Eumeces skiltonianus, Cmin increased from 2.5 to 4.7 ml O2 kg-1 m-1 between level and uphill locomotion. By taking the difference between Cmin for level and uphill locomotion, we found that the efficiency of performing vertical work during locomotion was 37 % for Coleonyx variegatus and 19 % for Eumeces skiltonianus. The similarity between the 1.9-fold difference in vertical efficiency and the 1.7-fold difference in the cost of transport on level ground is consistent with the hypothesis that nocturnal geckos have a lower cost of locomotion than other lizards because they can perform mechanical work during locomotion more efficiently.

Journal Article↗

PubMed1982

Quantification of the locomotive behavior of polymorphonuclear leukocytes in clot preparations.

Time-lapse videotape recordings of polymorphonuclear leukocytes (PMNs) from clot preparations were used to quantify the locomotive behavior of individual PMNs from normal subjects. Tracings derived from the videotapes allow one to quantify multiple parameters of the locomotive behavior of PMNs--direction, distance, rate, and angle of turn. The results obtained are reproducible from subject-to-subject and from preparation-to-preparation. The method allows the investigator to record the locomotive behavior of 100 cells simultaneously within a 5-min period and analyze the recording as time permits. We utilized this technique to compare the locomotive behavior of slow and fast PMNs (arbitrarily defined as cells that move less than or equal to 7.0 micrometer/min and greater than 7.0 micrometer/min mean rate of locomotion, respectively). The studies show that slow and fast PMNs, thus defined, differ not only in mean rate of locomotion but also in their rate of locomotion during periods of active locomotion, in the number of periods of inactivity/PMN/5 min (slow = 1.65 +/- 0.31; fast = 0.36 +/- 0.12), and in their turning behavior as measured by angle of turn (slow = 92 degrees +/- 39 degrees; fast = 39 degrees +/- 35 degrees). These results show that human PMNs from clot preparations are remarkably heterogeneous in their locomotive behavior, and the results suggest this heterogeneity is due to endogenous differences within cells.

Adult↗

PubMed1995

T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules.

T cell locomotion within the extracellular matrix may be mediated by cell adhesion molecules. We investigated the expression and function of beta 1- and beta 2-integrins and CD44 on human peripheral CD4+ and CD8+ lymphocytes locomoting in a 3-D type I collagen matrix. Paths of randomly selected T cells were digitized from time-lapse videorecordings and were quantitatively analyzed. After the blocking of CD49b with mAb Gi9, the locomotion of a defined locomotor subset (50% of spontaneously locomoting cells) was inhibited. Anti-CD49d mAb HP2/1 and an activating anti-CD44 mAb (J173), respectively, induced transient recruitment (< 1 h) of previously nonmotile cells (10 to 35%). In contrast to the J173-induced short-term locomotion, hyaluronan incorporated within the matrix promoted locomotion for > 2 h. No significant effects were present for anti-CD49f (GoH3) and -CD11a (25.3) mAbs. After the addition of IL-8 to the matrix, rapid induction of locomotion in 20 to 30% of the cells (control) was evident, which was virtually abolished by anti-alpha 2- and alpha 6-integrin, and -CD11a mAbs. Thus, the locomotion of nonactivated and IL-8-activated T cells may involve different sets of integrins. Using flow cytometry, the development of a CD49b+CD29highCD44lowL-selectinlow T cell phenotype independent of activation markers including CD25, CD27, CD28, VLA-4, and CD45RA- to CD45RO-transition was observed after 4 days in the matrix. The initial development of spontaneous locomotion in the collagen matrix, however, was not accompanied by alterations in CAM surface staining and, therefore, may involve functional CAM activation rather than involving an increase in surface expression.

Antibodies, Monoclonal↗

PubMed1997

Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices.

Locomotion of T lymphocytes within three-dimensional collagen matrices is regulated via different signaling states of the cells. Purified human CD4+ and CD8+ T cells developed a spontaneously locomoting subpopulation of about 25% of the whole population immediately after incorporation into a three-dimensional collagen matrix analyzed by time-lapse videomicroscopy. This spontaneous locomotion was accompanied by enhanced tyrosine phosphorylation of the focal adhesion kinase (FAK). Inhibition of protein tyrosine kinase (PTK) activity using genistein significantly reduced the spontaneous locomotory activity. This reduction was overcome by subsequent activation of protein kinase C (PKC) using PMA, which led to a persistent increase of locomotory activity to more than 60% of the cells. Thus, the PKC-driven type of locomotion was independent of PTK activity, whereas spontaneous locomotion was not altered by inhibition of PKC activity using calphostin C or inhibition of the serine/ threonine phosphatases pp1 and pp2A using okadaic acid. We presume that PTK activity, especially tyrosine phosphorylation of FAK, is decisively involved in the regulation of spontaneous T lymphocyte locomotion, which is independent of PKC activity. In contrast, PKC-driven locomotion is independent of tyrosine phosphorylation events, indicating that T lymphocyte locomotion is regulated by more than one signal transduction pathway. Furthermore, confocal microscopy analysis of phosphotyrosine residues, FAK, and PKC revealed an exclusive cellular distribution of these components, suggesting a regulation of T lymphocyte locomotion different from migration models developed for other cell types, which refer to a colocalization of FAK and PKC in focal adhesions.

CD4-Positive T-Lymphocytes↗

PubMed1985

Initiation of locomotion from the mesencephalic locomotor region: effects of selective brainstem lesions.

The effects of selected brainstem lesions on controlled treadmill locomotion produced by stimulation of the mesencephalic locomotor region (MLR) in postmamillary cats were determined in these experiments. The importance for the initiation of locomotion of projections from the MLR to rostral brainstem structures, described in a preceding paper, were examined by selective lesioning or by adjusting the level of the decerebration. The role played by the lateral vestibulospinal tract (LVST) in the initiation of locomotion was examined by lesioning Deiters' nucleus bilaterally. Contrary to previous claims, the results of the present experiments show that areas of the brainstem rostral to the MLR are not required for the initiation of locomotion by MLR stimulation. This finding eliminates the ventral tegmental area of Tsai and the substantia nigra, both implicated in the initiation of locomotion, as required participants in MLR stimulated locomotion. Bilateral Deiters' nucleus (DN) lesions did not significantly affect the initiation of locomotion from the MLR, nor did such lesions alter in a systematic fashion the amplitude or timing of EMG activity in flexor or extensor muscles of the hindlimb during MLR evoked walking. Joint angle changes during the locomotor cycle were also essentially unaltered by DN lesions. The significance of these findings regarding the brainstem structures which must be involved in the initiation of locomotion are discussed.

Animals↗

PubMed1996

Effects of dopaminergic and glutamatergic receptor antagonists on the establishment and expression of conditioned locomotion to cocaine in rats.

A series of experiments were conducted to investigate the role of dopaminergic D1 and D2 and glutamatergic NMDA and AMPA/kainate receptors on the establishment and expression of cocaine-induced conditioned locomotion in rats. In the first experiment conditioned locomotion was demonstrated by testing the animals in an environment previously associated with 15 mg/kg i.p. cocaine. The D2-receptor antagonist (-)-sulpiride (50 and 100 mg/kg i.p.) administered before cocaine during the conditioning phase did not modify the establishment of conditioned locomotion whereas when administered before testing only at the higher dose it partially reduced rats' locomotion in the absence of cocaine (expression). At the higher dose (0.1 mg/kg i.p.) the D1-receptor antagonist SCH 23390 attenuated the expression of cocaine-induced conditioned locomotion whereas the lower dose (0.03 mg/kg i.p.) had no effect. Both doses of the NMDA receptor antagonist MK-801 (0.125 and 0.25 mg/kg i.p.) blocked the development of cocaine-induced conditioned locomotion but neither dose, when administered before testing, modified locomotion in the absence of cocaine. Both doses of the AMPA/kainate receptor antagonist DNQX administered intracerebroventricularly (1 and 3 micrograms/rat) blocked cocaine-induced conditioned locomotion when given before cocaine during conditioning but when given before testing only the higher dose attenuated the conditioned activity. The results confirm the importance of the interaction between glutamatergic and dopaminergic systems for the conditional factors maintaining drug seeking behaviour. The findings may have implications for the treatment of cocaine craving and relapse.

Analysis of Variance↗