Dynamic Sensorimotor Interactions in Locomotion

2006 ◽  
Vol 86 (1) ◽  
pp. 89-154 ◽  
Author(s):  
Serge Rossignol ◽  
Réjean Dubuc ◽  
Jean-Pierre Gossard

Locomotion results from intricate dynamic interactions between a central program and feedback mechanisms. The central program relies fundamentally on a genetically determined spinal circuitry (central pattern generator) capable of generating the basic locomotor pattern and on various descending pathways that can trigger, stop, and steer locomotion. The feedback originates from muscles and skin afferents as well as from special senses (vision, audition, vestibular) and dynamically adapts the locomotor pattern to the requirements of the environment. The dynamic interactions are ensured by modulating transmission in locomotor pathways in a state- and phase-dependent manner. For instance, proprioceptive inputs from extensors can, during stance, adjust the timing and amplitude of muscle activities of the limbs to the speed of locomotion but be silenced during the opposite phase of the cycle. Similarly, skin afferents participate predominantly in the correction of limb and foot placement during stance on uneven terrain, but skin stimuli can evoke different types of responses depending on when they occur within the step cycle. Similarly, stimulation of descending pathways may affect the locomotor pattern in only certain phases of the step cycle. Section ii reviews dynamic sensorimotor interactions mainly through spinal pathways. Section iii describes how similar sensory inputs from the spinal or supraspinal levels can modify locomotion through descending pathways. The sensorimotor interactions occur obviously at several levels of the nervous system. Section iv summarizes presynaptic, interneuronal, and motoneuronal mechanisms that are common at these various levels. Together these mechanisms contribute to the continuous dynamic adjustment of sensorimotor interactions, ensuring that the central program and feedback mechanisms are congruous during locomotion.

2001 ◽  
Vol 85 (6) ◽  
pp. 2516-2536 ◽  
Author(s):  
Nathalie Giroux ◽  
Tomás A. Reader ◽  
Serge Rossignol

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 α2-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 α2 agonist, clonidine, and the antagonist (16α, 17α)-17-hydroxy yohimbine-16-carboxylic acid methyl ester hydrochloride (yohimbine), injected intrathecally at L3–L4before and after spinalization in the same cats chronically implanted with electrodes to record electromyograms (EMGs). In intact cats, clonidine (50–150 μg/100 μl) 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 μg/100 μl) caused major walking difficulties characterized by asymmetric stepping, stumbling with poor lateral stability, and, at smaller doses (400 μg/100 μl), 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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruifang Guan ◽  
Tengfei Lian ◽  
Bing-Rui Zhou ◽  
Emily He ◽  
Carl Wu ◽  
...  

AbstractAccurate chromosome segregation relies on the specific centromeric nucleosome–kinetochore interface. In budding yeast, the centromere CBF3 complex guides the deposition of CENP-A, an H3 variant, to form the centromeric nucleosome in a DNA sequence-dependent manner. Here, we determine the structures of the centromeric nucleosome containing the native CEN3 DNA and the CBF3core bound to the canonical nucleosome containing an engineered CEN3 DNA. The centromeric nucleosome core structure contains 115 base pair DNA including a CCG motif. The CBF3core specifically recognizes the nucleosomal CCG motif through the Gal4 domain while allosterically altering the DNA conformation. Cryo-EM, modeling, and mutational studies reveal that the CBF3core forms dynamic interactions with core histones H2B and CENP-A in the CEN3 nucleosome. Our results provide insights into the structure of the budding yeast centromeric nucleosome and the mechanism of its assembly, which have implications for analogous processes of human centromeric nucleosome formation.


1997 ◽  
Vol 01 (02) ◽  
pp. 95-109 ◽  
Author(s):  
W. Herzog ◽  
T. R. Leonard

The dynamic properties of the cat soleus muscle were studied in freely walking animal preparations. The force and EMG responses of the soleus following supramaximal, ins tants of the step cycle. The sensorimotor interactions of soleus with the medial head of the gastrocnemius (a functional agonist of the soleus at the ankle) and the tibialis anterior (a functional antagonist of soleus at the ankle) were studied by measuring their force and EMG responses following the artifical stimulation of the soleus nerve. Supramaximal nerve stimulation showed distinct increases in the soleus forces during the entire swing phase and the second part (after peak forces had been reached) of the stance phase. Soleus forces could only be increased slightly in the first part of stance (from paw contact to peak force). These results suggest that force production of the soleus is virtually maximal during the early phases of stance but is submaximal for the remainder of the step cycle. Forces and EMGs of the medial gastrocnemius muscle were affected by the soleus nerve stimulation only in the latter part of the swing phase. In these cases, the force and EMG of the medial gastrocnemius were reduced significantly for the step cycle following the perturbation. The active force production of soleus during late swing causes an inhibition of medial gastrocnemius activity and force. Forces and EMGs of the tibialis anterior muscle were always affected by the soleus nerve stimulation during the swing phase of the step cycle. In these case, the force EMG of the medial gastrocnemius were reduced significantly for the step cycle following the perturbation. The active force production of soleus during late swing causes an inhibition of medial gastrocnemius activity and force. Forces and EMGs of the tibialis anterior muscle were always affected by the soleus nerve stimulation during the swing phase of the step cycle. In these instances, forces and EMGs of the tibialis anterior were significantly increased compared to step cycles preceding or following the perturbation. Part of the force enhancement is caused by the stretch of the activated tibialis anterior by the soleus, and part of the enhancement is caused by reflex activation. No effects on forces or EMGs of the tibialis anterior were observed when the soleus nerve stimulation showed its effects during the stance phase of the step cycle. The results of theis study suggest that the magnitude and the quality of ensorimotor interactions of soleus with medial gastrocnemius and tibialis anterior depend on the phase of the step cycle. The strongest interactions appear to exist during the swing phase; no observable interactions were found during stance.


2000 ◽  
Vol 83 (4) ◽  
pp. 2093-2102 ◽  
Author(s):  
A. M. Schillings ◽  
B.M.H. van Wezel ◽  
Th. Mulder ◽  
J. Duysens

Although many studies have investigated reflexes after stimulation of either cutaneous or proprioceptive afferents, much less is known about responses after more natural perturbations, such as stumbling over an obstacle. In particular, the phase dependency of these responses and their relation to the stumbling behavior has received little attention. Hence response strategies during stumbling reactions after perturbations at different times in the swing phase of gait were studied. While subjects walked on a treadmill, a rigid obstacle unexpectedly obstructed the forward sway of the foot. All subjects showed an “elevating strategy” after early swing perturbations and a “lowering strategy” after late swing perturbations. During the elevating strategy, the foot was directly lifted over the obstacle through extra knee flexion assisted by ipsilateral biceps femoris (iBF) responses and ankle dorsiflexion assisted by tibialis anterior (iTA) responses. Later, large rectus femoris (iRF) activations induced knee extension to place the foot on the treadmill. During the lowering strategy, the foot was quickly placed on the treadmill and was lifted over the obstacle in the subsequent swing. Foot placement was actively controlled by iRF and iBF responses related to knee extension and deceleration of the forward sway. Activations of iTA mostly preceded the main ipsilateral soleus (iSO) responses. For both strategies, four response peaks could be distinguished with latencies of ∼40 ms (RP1), ∼75 ms (RP2), ∼110 ms (RP3), and ∼160 ms (RP4). The amplitudes of these response peaks depended on the phase in the step cycle. The phase-dependent modulation of the responses could not be accounted for by differences in stimulation or in background activity and therefore is assumed to be premotoneuronal in origin. In mid swing, both the elevating and lowering strategy could occur. For this phase, the responses of the two strategies could be compared in the absence of phase-dependent response modulation. Both strategies had the same initial electromyographic responses till ∼100 ms (RP1-RP2) after perturbation. The earliest response (RP1) is assumed to be a short-latency stretch reflex evoked by the considerable impact of the collision, whereas the second (RP2) has features reminiscent of cutaneous and proprioceptive responses. Both these responses did not determine the behavioral response strategy. The functionally important response strategies depended on later responses (RP3-RP4). These data suggest that during stumbling reactions, as a first line of defense, the CNS releases a relatively aspecific response, which is followed by an appropriate behavioral response to avoid the obstacle.


1987 ◽  
Vol 253 (4) ◽  
pp. G434-G438 ◽  
Author(s):  
J. R. Grider ◽  
A. Arimura ◽  
G. M. Makhlouf

The role of somatostatin neurons in the regulation of peristalsis was examined in segments of rat colon that permit separate characterization of the ascending contraction and descending relaxation components of the peristaltic reflex. Release of somatostatin and vasoactive intestinal peptide (VIP) increased significantly only during descending relaxation. Preincubation of the segment with somatostatin antiserum (final concentration 1:40) decreased VIP release and descending relaxation. Addition of somatostatin (1 nM to 1 microM) augmented VIP release and descending relaxation in a concentration-dependent manner. Together the results implied that the increase in somatostatin release was coupled to, and responsible for, the increase in VIP release, which in turn was responsible for descending relaxation. The results are consistent with the topography of myenteric VIP neurons (which project into circular muscle) and somatostatin neurons (which project caudad within the plexus) and the pharmacological properties of the two peptides. Somatostatin antiserum had no effect on basal VIP release or ascending contraction, indicating that somatostatin neurons were not involved in the regulation of ascending contraction. The study suggests that somatostatin neurons of the myenteric plexus act as facilitatory interneurons in descending pathways.


2014 ◽  
Vol 111 (11) ◽  
pp. 2264-2275 ◽  
Author(s):  
Maria Knikou ◽  
Chaithanya K. Mummidisetty

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking.


1999 ◽  
Vol 81 (6) ◽  
pp. 2914-2922 ◽  
Author(s):  
K. Hase ◽  
R. B. Stein

Turning strategies during human walking. The mechanisms involved in rapidly turning during human walking were studied. Subjects were asked to walk at a comfortable speed and to turn toward the instructed direction as soon as they felt an electrical stimulus to the superficial peroneal nerve. Stimuli were presented repeatedly at random over 10- to 15-min periods of walking for turning in both directions. Electromyograms (EMGs), joint angular movements of the right leg, and forces under both feet were recorded. The step cycle was divided into 16 parts, and the responses to stimuli in each part were analyzed separately. Two turning strategies were used, depending on which leg was placed in front for braking. For example, to turn to the right when the right foot was placed in front, subjects generally altered direction by spinning the body around the right foot (spin turn). To turn left when the right foot was in front, subjects shifted weight to the right leg, externally rotated the left hip, stepped onto the left leg, and continued turning until the right leg stepped in the new direction (step turn). The step turn is easy and stable because the base of support during the turn is much wider than in the spin turn, so some subjects used it in all parts of the cycle. Initially, the deceleration of walking is similar to a rapid stopping task, which has been previously examined. The deceleration mechanism involves a sequence of distal-to-proximal activation of muscles on one side of the body (soleus, biceps femoris, and erector spinae). This pattern is similar to the “ankle strategy” used in postural control during forward sway. The control of foot placement in the swing leg and muscle activities for rotating the trunk in the stance leg occurred within a step after the cue. The action of ankle inverters and elevation of the pelvis by activity of gluteus medius may contribute to the control of trunk rotation. This activity was closely related to the timing of the opposite foot strike, independent of the part of the step cycle when the stimulus was applied. In most subjects, the turn was completed without resetting the underlying walking rhythm. This first EMG analysis of rapid turning shows how common strategies for postural sway and stopping can be combined with one of two turning strategies. This simplifies the complex task of turning at a random time in the step cycle.


2020 ◽  
Vol 133 (14) ◽  
pp. jcs248591
Author(s):  
Sabine A. G. Cuijpers ◽  
Edwin Willemstein ◽  
Jan G. Ruppert ◽  
Daphne M. van Elsland ◽  
William C. Earnshaw ◽  
...  

ABSTRACTCell division ends when two daughter cells physically separate via abscission, the cleavage of the intercellular bridge. It is not clear how the anti-parallel microtubule bundles bridging daughter cells are severed. Here, we present a novel abscission mechanism. We identified chromokinesin KIF4A, which is adjacent to the midbody during cytokinesis, as being required for efficient abscission. KIF4A is regulated by post-translational modifications. We evaluated modification of KIF4A by the ubiquitin-like protein SUMO. We mapped lysine 460 in KIF4A as the SUMO acceptor site and employed CRISPR-Cas9-mediated genome editing to block SUMO conjugation of endogenous KIF4A. Failure to SUMOylate this site in KIF4A delayed cytokinesis. SUMOylation of KIF4A enhanced the affinity for the microtubule destabilizer stathmin 1 (STMN1). We here present a new level of abscission regulation through the dynamic interactions between KIF4A and STMN1 as controlled by SUMO modification of KIF4A.


1999 ◽  
Vol 81 (5) ◽  
pp. 2297-2315 ◽  
Author(s):  
Marie-Josée Rho ◽  
Sylvain Lavoie ◽  
Trevor Drew

Effects of red nucleus microstimulation on the locomotor pattern and timing in the intact cat: a comparison with the motor cortex. To determine the extent to which the rubrospinal tract is capable of modifying locomotion in the intact cat, we applied microstimulation (cathodal current, 330 Hz; pulse duration 0.2 ms; maximal current, 25 μA) to the red nucleus during locomotion. The stimuli were applied either as short trains (33 ms) of impulses to determine the capacity of the rubrospinal tract to modify the level of electromyographic (EMG) activity in different flexors and extensors at different phases of the step cycle or as long trains (200 ms) of pulses to determine the effect of the red nucleus on cycle timing. Stimuli were also applied with the cat at rest (33-ms train). This latter stimulation evoked short-latency (average = 11.8–19.0 ms) facilitatory responses in all of the physiological flexor muscles of the forelimb that were recorded; facilitatory responses were also common in the elbow extensor, lateral head of triceps but were rare in the physiological wrist and digit extensor, palmaris longus. Responses were still evoked in most muscles when the current was decreased to near threshold (3–10 μA). Stimulation during locomotion with the short trains of stimuli evoked shorter-latency (average = 6.0–12.5 ms) facilitatory responses in flexor muscles during the swing phase of locomotion and, except in the case of the extensor digitorum communis, evoked substantially smaller responses in stance. The same stimuli also evoked facilitatory responses in the extensor muscles during swing and produced more complex effects involving both facilitation and suppression in stance. Increasing the duration of the train to 200 ms modified the amplitude and duration of the EMG activity of both flexors and extensors but had little significant effect on the cycle duration. In contrast, whereas stimulation of the motor cortex with short trains of stimuli during locomotion had very similar effects to that of the red nucleus, increasing the train duration to 200 ms frequently produced a marked reset of the step cycle by curtailing stance and initiating a new period of swing. The results suggest that whereas both the motor cortex and the red nucleus have access to the interneuronal circuits responsible for controlling the structure of the EMG activity in the step cycle, only the motor cortex has access to the circuits responsible for controlling cycle timing.


2010 ◽  
Vol 104 (2) ◽  
pp. 1119-1133 ◽  
Author(s):  
Grégory Barrière ◽  
Alain Frigon ◽  
Hugues Leblond ◽  
Janyne Provencher ◽  
Serge Rossignol

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3–5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.


Sign in / Sign up

Export Citation Format

Share Document