Mikhail G. Sirota

Activity of Different Classes of Neurons of the Motor Cortex during Locomotion

This study examines the activity of different classes of neurons of the motor cortex in the rabbit during two locomotion tasks: a simple (on a flat surface) and a complex (overstepping a series of barriers) locomotion. Four classes of efferent neurons were studied: corticocortical (CC) neurons with ipsilateral projection (CCIs), those with contralateral projection (CCCs), descending corticofugal neurons of layer V (CF5s), and those of layer VI (CF6s). In addition, one class of inhibitory interneurons (SINs) was investigated. CF5 neurons and SINs were the only groups that were strongly active during locomotion. In most of these neurons a clear-cut modulation of discharge in the locomotion rhythm was observed. During simple locomotion, CF5s and SINs were preferentially active in opposite phases of the step cycle, suggesting that SINs contribute to formation of the step-related pattern of CF5s. Transition from simple to complex locomotion was associated with changes of the discharge pattern of the majority of CF5 neurons and SINs. In contrast to CF5 neurons, other classes of efferent neurons (CCI, CCC, CF6) were much less active during both simple and complex locomotion. That suggests that CC interactions, both within a hemisphere (mediated by CCIs) and between hemispheres (mediated by CCCs), as well as corticothalamic interactions via CF6 neurons are not essential for motor coordination during either simple or complex locomotion tasks.

Activity of Different Classes of Neurons of the Motor Cortex during Postural Corrections

The dorsal side-up body orientation in quadrupeds is maintained by a postural system that is driven by sensory feedback signals. The spinal cord, brainstem, and cerebellum play essential roles in postural control, whereas the role of the forebrain is unclear. In the present study we investigated whether the motor cortex is involved in maintenance of the dorsal side-up body orientation. We recorded activity of neurons in the motor cortex in awake rabbits while animals maintained balance on a platform periodically tilting in the frontal plane. The tilts evoked postural corrections, i.e., extension of the limbs on the side moving down and flexion on the opposite side. Because of these limb movements, rabbits maintained body orientation close to the dorsal side up. Four classes of efferent neurons were studied: descending corticofugal neurons of layer V (CF5s), those of layer VI (CF6s), corticocortical neurons with ipsilateral projection (CCIs), and those with contralateral projection (CCCs). One class of inhibitory interneurons [suspected inhibitory neurons (SINs)] was also investigated. CF5 neurons and SINs were strongly active during postural corrections. In most of these neurons, a clear-cut modulation of discharge in the rhythm of tilting was observed. This finding suggests that the motor cortex is involved in postural control. In contrast to CF5 neurons, other classes of efferent neurons (CCI, CCC, CF6) were much less active during postural corrections. This suggests that corticocortical interactions, both within a hemisphere (mediated by CCIs) and between hemispheres (mediated by CCCs), as well as corticothalamic interactions via CF6 neurons are not essential for motor coordination during postural corrections.

Differences in Movement Mechanics, Electromyographic, and Motor Cortex Activity Between Accurate and Nonaccurate Stepping

What are the differences in mechanics, muscle, and motor cortex activity between accurate and nonaccurate movements? We addressed this question in relation to walking. We assessed full-body mechanics (229 variables), activity of 8 limb muscles, and activity of 63 neurons from the motor cortex forelimb representation during well-trained locomotion with different demands on the accuracy of paw placement in cats: during locomotion on a continuous surface and along horizontal ladders with crosspieces of different widths. We found that with increasing accuracy demands, cats assumed a more bent-forward posture (by lowering the center of mass, rotating the neck and head down, and by increasing flexion of the distal joints) and stepped on the support surface with less spatial variability. On the ladder, the wrist flexion moment was lower throughout stance, whereas ankle and knee extension moments were higher and hip moment was lower during early stance compared with unconstrained locomotion. The horizontal velocity time histories of paws were symmetric and smooth and did not differ among the tasks. Most of the other mechanical variables also did not depend on accuracy demands. Selected distal muscles slightly enhanced their activity with increasing accuracy demands. However, in a majority of motor cortex cells, discharge rate means, peaks, and depths of stride-related frequency modulation changed dramatically during accurate stepping as compared with simple walking. In addition, in 30% of neurons periods of stride-related elevation in firing became shorter and in 20-25% of neurons activity or depth of frequency modulation increased, albeit not linearly, with increasing accuracy demands. Considering the relatively small changes in locomotor mechanics and substantial changes in motor cortex activity with increasing accuracy demands, we conclude that during practiced accurate stepping the activity of motor cortex reflects other processes, likely those that involve integration of visual information with ongoing locomotion.

Three Channels of Corticothalamic Communication during Locomotion

We studied the flow of corticothalamic (CT) information from the motor cortex of the cat during two types of locomotion: visually guided (cortex dependent) and unguided. Spike trains of CT neurons in layers V (CT5s) and VI (CT6s) were examined. All CT5s had fast-conducting axons (<2 ms conduction time), and nearly all showed step-phase-related activity (94%), sensory receptive fields (100%), and spontaneous activity (100%). In contrast, conduction times along CT6 axons were much slower, with bimodal peaks occurring at 6 and 32 ms. Remarkably, almost none of the slowest conducting CT6s showed step-related activity, sensory receptive fields, or spontaneous activity. As a group, these enigmatic neurons were all but silent. Some of the CT6s with moderately conducting axons showed step-related behavior (35%), and this response was more precisely timed than that of the CT5s. We propose distinct functional roles for these diverse corticothalamic populations.

Activity of Red Nucleus Neurons in the Cat during Postural Corrections

The dorsal-side-up body posture in standing quadrupeds is maintained by the postural system, which includes spinal and supraspinal mechanisms driven by somatosensory inputs from the limbs. A number of descending tracts can transmit supraspinal commands for postural corrections. The first aim of this study was to understand whether the rubrospinal tract participates in their transmission. We recorded activity of red nucleus neurons (RNNs) in the cat maintaining balance on the periodically tilting platform. Most neurons were identified as rubrospinal ones. It was found that many RNNs were profoundly modulated by tilts, suggesting that they transmit postural commands. The second aim of this study was to examine the contribution of sensory inputs from individual limbs to posture-related RNN modulation. Each RNN was recorded during standing on all four limbs, as well as when two or three limbs were lifted from the platform and could not signal platform displacements. By comparing RNN responses in different tests, we found that the amplitude and phase of responses in the majority of RNNs were determined primarily by sensory input from the corresponding (fore or hind) contralateral limb, whereas inputs from other limbs made a much smaller contribution to RNN modulation. These findings suggest that the rubrospinal system is primarily involved in the intralimb postural coordination, i.e., in the feedback control of the corresponding limb and, to a lesser extent, in the interlimb coordination. This study provides a new insight into the formation of supraspinal motor commands for postural corrections.

Activity of pyramidal tract neurons in the cat during standing and walking on an inclined plane

To keep balance when standing or walking on a surface inclined in the roll plane, the cat modifies its body configuration so that the functional length of its right and left limbs becomes different. The aim of the present study was to assess the motor cortex participation in the generation of this left/right asymmetry. We recorded the activity of fore‐ and hindlimb‐related pyramidal tract neurons (PTNs) during standing and walking on a treadmill. A difference in PTN activity at two tilted positions of the treadmill (± 15 deg) was considered a positional response to surface inclination. During standing, 47% of PTNs exhibited a positional response, increasing their activity with either the contra‐tilt (20%) or the ipsi‐tilt (27%). During walking, PTNs were modulated in the rhythm of stepping, and tilts of the supporting surface evoked positional responses in the form of changes to the magnitude of modulation in 58% of PTNs. The contra‐tilt increased activity in 28% of PTNs, and ipsi‐tilt increased activity in 30% of PTNs. We suggest that PTNs with positional responses contribute to the modifications of limb configuration that are necessary for adaptation to the inclined surface. By comparing the responses to tilts in individual PTNs during standing and walking, four groups of PTNs were revealed: responding in both tasks (30%); responding only during standing (16%); responding only during walking (30%); responding in none of the tasks (24%). This diversity suggests that common and separate cortical mechanisms are used for postural adaptation to tilts during standing and walking.

Maintenance of Lateral Stability During Standing and Walking in the Cat

During free behaviors animals often experience lateral forces, such as collisions with obstacles or interactions with other animals. We studied postural reactions to lateral pulses of force (pushes) in the cat during standing and walking. During standing, a push applied to the hip region caused a lateral deviation of the caudal trunk, followed by a return to the initial position. The corrective hindlimb electromyographic (EMG) pattern included an initial wave of excitation in most extensors of the hindlimb contralateral to push and inhibition of those in the ipsilateral limb. In cats walking on a treadmill with only hindlimbs, application of force also caused lateral deviation of the caudal trunk, with subsequent return to the initial position. The type of corrective movement depended on the pulse timing relative to the step cycle. If the force was applied at the end of the stance phase of one of the limbs or during its swing phase, a lateral component appeared in the swing trajectory of this limb. The corrective step was directed either inward (when the corrective limb was ipsilateral to force application) or outward (when it was contralateral). The EMG pattern in the corrective limb was characterized by considerable modification of the hip abductor and adductor activity in the perturbed step. Thus the basic mechanisms for balance control in these two forms of behavior are different. They perform a redistribution of muscle activity between symmetrical limbs (in standing) and a reconfiguration of the base of support during a corrective lateral step (in walking).

Interlimb postural coordination in the standing cat.

The dorsal‐side‐up body posture in standing quadrupeds is maintained by coordinated activity of four limbs. We studied this coordination in the cat standing on the platform periodically tilted in the frontal plane. By suspending different body parts, we unloaded one, two, or three limbs. The activity of selected extensor muscles and the contact forces under the limbs were recorded. With all four limbs on the platform, extensors of the fore‐ and hindlimbs increased their activity in parallel during ipsilateral downward tilt. With two forelimbs on the platform, this muscular pattern persisted in the forelimbs and in the suspended hindlimbs. With two hindlimbs on the platform, the muscular pattern persisted only in the hindlimbs, but not in the suspended forelimbs. These results suggest that coordination between the two girdles is based primarily on the influences of the forelimbs upon the hindlimbs. However, these influences do not necessarily determine the responses to tilt in the hindlimbs. This was demonstrated by antiphase tilting of the fore‐ and hindquarters. Under these conditions, the extensors of the fore‐ and hindlimbs appeared uncoupled and modulated in antiphase, suggesting an independent control of posture in the fore‐ and hindquarters. With only one limb supporting the shoulder or hip girdle, a muscular pattern with normal phasing was observed in both limbs of that girdle. This finding suggests that reflex mechanisms of an individual limb generate only a part of postural corrections; another part is produced on the basis of crossed influences.

Signals from the ventrolateral thalamus to the motor cortex during locomotion

The activity of the motor cortex during locomotion is profoundly modulated in the rhythm of strides. The source of modulation is not known. In this study we examined the activity of one of the major sources of afferent input to the motor cortex, the ventrolateral thalamus (VL). Experiments were conducted in chronically implanted cats with an extracellular single-neuron recording technique. VL neurons projecting to the motor cortex were identified by antidromic responses. During locomotion, the activity of 92% of neurons was modulated in the rhythm of strides; 67% of cells discharged one activity burst per stride, a pattern typical for the motor cortex. The characteristics of these discharges in most VL neurons appeared to be well suited to contribute to the locomotion-related activity of the motor cortex. In addition to simple locomotion, we examined VL activity during walking on a horizontal ladder, a task that requires vision for correct foot placement. Upon transition from simple to ladder locomotion, the activity of most VL neurons exhibited the same changes that have been reported for the motor cortex, i.e., an increase in the strength of stride-related modulation and shortening of the discharge duration. Five modes of integration of simple and ladder locomotion-related information were recognized in the VL. We suggest that, in addition to contributing to the locomotion-related activity in the motor cortex during simple locomotion, the VL integrates and transmits signals needed for correct foot placement on a complex terrain to the motor cortex.

Influences of sensory input from the limbs on feline corticospinal neurons during postural responses.

The dorsal‐side‐up body posture of standing quadrupeds is maintained by coordinated activity of all limbs. Somatosensory input from the limbs evokes postural responses when the supporting surface is perturbed. The aim of this study was to reveal the contribution of sensory inputs from individual limbs to the posture‐related modulation of pyramidal tract neurons (PTNs) arising in the primary motor cortex. We recorded the activity of PTNs from the limb representation of motor cortex in the cat maintaining balance on a platform periodically tilted in the frontal plane. Each PTN was recorded during standing on four limbs, and when two or three limbs were lifted from the platform and thus did not signal its displacement to motor cortex. By comparing PTN responses to tilts in different tests we found that the amplitude and the phase of the response in the majority of them were determined primarily by the sensory input from the corresponding contralateral limb. In a portion of PTNs, this input originated from afferents of the peripheral receptive field. Sensory input from the ipsilateral limb, as well as input from limbs of the other girdle made a much smaller contribution to the PTN modulation. These results show that, during postural activity, a key role of PTNs is the feedback control of the corresponding contralateral limb and, to a lesser extent, the coordination of posture within a girdle and between the two girdles.