Reticulospinal neurons in the pontomedullary reticular formation of the monkey (Macaca fascicularis).

Recent neurophysiological studies indicate a role for reticulospinal neurons of the pontomedullary reticular formation (PMRF) in motor preparation and goal-directed reaching in the monkey. Although the macaque monkey is an important model for such investigations, little is known regarding the organization of the PMRF in the monkey. In the present study, we investigated the distribution of reticulospinal neurons in the macaque. Bilateral injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) were made into the cervical spinal cord. A wide band of retrogradely labeled cells was found in the gigantocellular reticular nucleus (Gi) and labeled cells continued rostrally into the caudal pontine reticular nucleus (PnC) and into the oral pontine reticular nucleus (PnO). Additional retrograde tracing studies following unilateral cervical spinal cord injections of cholera toxin subunit B revealed that there were more ipsilateral (60%) than contralateral (40%) projecting cells in Gi, while an approximately 50:50 ratio contralateral to ipsilateral split was found in PnC and more contralateral projections arose from PnO. Reticulospinal neurons in PMRF ranged widely in size from over 50 microm to under 25 microm across the major somatic axis. Labeled giant cells (soma diameters greater than 50 microm) comprised a small percentage of the neurons and were found in Gi, PnC and PnO. The present results define the origins of the reticulospinal system in the monkey and provide an important foundation for future investigations of the anatomy and physiology of this system in primates.

Changes in the control of arm position, movement, and thalamic discharge during local inactivation in the globus pallidus of the monkey.

1. To examine the effect of disruption of basal ganglia output on limb stability and movement, muscimol was injected into the internal globus pallidus (GPi) of monkeys trained to make arm movements to visible or remembered targets in a two-dimensional workspace. 2. Injections of as little as 0.25 micrograms muscimol at GPi sites at which pallidal neurons with arm movement activity had been recorded were followed by drift of the contralateral arm within < 10 min. Drift was usually in the flexor direction. Injections at a few sites in or near the external pallidal segment sometimes were followed by extensor drift. 3. Drift was active (accompanied by activation of agonist muscles), but could be overcome by the animal, resulting in an oscillating movement off and on the required position. 4. The pallidal-receiving (PR) area of the thalamus was identified by recording the response of thalamic neurons to stimulation in the globus pallidus. The activity of 15 neurons identified as PR cells (n = 6) or within the PR region was recorded both before and after injection of muscimol into GPi. After the injection, the tonic discharge increased during the hold period in 47% of the cells studied. When postural drift also occurred, there was a close temporal correlation between the postinjection time at which drift occurred and the time at which the tonic discharge rate increased in thalamic neurons that were clearly related to arm movement. 5. The peak velocity of arm movements to visible or remembered visual target locations was decreased after injection of muscimol into GPi, sometimes with an increase in movement time. 6. The firing rate of PR thalamic neurons after injection of muscimol was also increased during the perimovement period. Because of the increase in the tonic discharge rate, however, the phasic movement-related change in activity could stay the same or even decrease. Postinjection changes in this movement-related phasic activity, however, were not necessarily coincident with changes in peak movement velocity. 7. Changes in reaction time were variable after injection of muscimol. In some cases it was increased, and in others decreased. The time of onset of phasic movement-related changes in the activity of PR neurons studied was not altered by the injection. 8. Our data indicate that the tonic inhibitory output of GPi, in particular to the cortical motor areas, is especially important in the maintenance of postural stability. In the absence of normal pallidal output, desired limb position can be achieved on the basis of either current or prior visual cues, but targeted movements are slowed.

Contrasting locations of pallidal-receiving neurons and microexcitable zones in primate thalamus.

1. In two awake, juvenile male Macaca fascicularis monkeys, microstimulation was applied in ventralis anterior (VA), ventralis lateralis (VL), or ventralis posterior lateralis (VPL) of the thalamus. Thalamic recording was used to identify the region that contained pallidal-receiving (PR) thalamic neurons, cells that responded orthodromically to stimulation in the internal pallidal segment (GPi). Thalamic stimulation was used to elicit motor responses. Penetrations in the thalamus and the pallidum focused on areas with activity related to contralateral arm movement. Fifty-one PR cells were identified electrophysiologically in VL oralis (VLo), VL caudalis (VLc) and VA pars parvocellularis (VApc). 2. With a subject at rest, trains of stimuli were applied through the thalamic microelectrode. Palpable or visible muscle twitches or joint movements were evoked by short trains (12 pulses) of stimuli applied in VLc and VPL oralis (VPLo); thresholds there ranged from 5 to 75 microA. In VA and VLo, areas where PR neurons were located, even longer trains (24 pulses) of stimuli with currents up to 200 microA usually failed to evoke movement. In the caudal portions of VLo, near VPLo, there were some microexcitable sites found near PR cells where stimuli at approximately 50 microA elicited movement. 3. From microstimulation studies combined with histological reconstruction, Ashe and co-workers hypothesized that microexcitable zones were cerebellar receiving areas (CR) and nonexcitable zones were PR areas. Our data support theirs and add electrophysiological identification of PR areas. Further, we injected wheat germ agglutinin-horseradish peroxidase (WGA-HRP) into the thalamus at one of the more rostral microexcitable sites, just caudal and lateral to identified PR cells. The tetra-methyl benzidine-reacted HRP label was found in the contralateral deep cerebellar nuclei (DCN) but not in ipsilateral GPi, showing that even this rostral microexcitable zone was a CR area. 4. Together with evidence from the literature, the data are consistent with the hypothesis that PR cells have relatively weak access to spinal-destined motor outputs, whereas thalamocortical neurons from VPLo and VLc have more secure access. In addition to characteristics of cell discharge and responses to somatosensory stimulation, microexcitability may be a further aid in tentative electro-physiological identification of PR versus CR areas of the motor thalamus without necessarily recording thalamic neuronal responses to stimulation in GPi or the DCN.

Adaptive control for backward quadrupedal walking V. Mutable activation of bifunctional thigh muscles.

1. In this, the fifth article in a series to assess changes in posture, hindlimb dynamics, and muscle synergies associated with backward (BWD) quadrupedal walking, we compared the recruitment of three biarticular muscles of the cat's anterior thigh (anterior sartorius, SAa; medial sartorius, SAm; rectus femoris, RF) for forward (FWD) and BWD treadmill walking. Electromyography (EMG) records from these muscles, along with those of two muscles (semitendinosus, ST; anterior biceps femoris, ABF) studied previously in this series, were synchronized with kinematic data digitized from high-speed ciné film for unperturbed steps and steps in which a stumbling corrective reaction was elicited during swing. 2. During swing, the relative timing of EMG activity for the unifunctional SAm (hip and knee flexor) was similar for unperturbed steps of FWD and BWD walking. The SAm was active before paw lift off and remained active during most of swing (75%) for both forms of walking, but there was a marked decrease in EMG amplitude after paw off during BWD and not FWD swing. In contrast, the relative timing of EMG activity for the SAa and RF, two bifunctional muscles (hip flexors, knee extensors), was different for FWD and BWD swing. During FWD swing, the SAa and the RF (to a lesser extent) were coactive with the SAm; however, during BWD swing, the SAa and RF were active just before paw lift off and then inactive for the rest of swing until just before paw contact (see 3). Thus the swing-phase activity of the SAa and RF was markedly shorter for BWD than FWD swing. 3. Activity in SAa and RF was also different during FWD and BWD stance. The RF was consistently active from mid-to-late stance of FWD walking, and the SAa was also active during this period in some FWD steps. During the stance phase of BWD walking, however, the onset of activity in both muscles consistently shifted to early stance as both muscles became active just before paw contact (the E1 phase). Activity in RF consistently persisted through most of BWD stance. The duration of SAa recruitment during BWD stance was more variable across cats with offsets ranging from mid- to late stance. 4. The activation patterns of the biarticular anterior thigh muscles during stumbling corrective reactions were, in general, similar to their different activations during FWD and BWD swing. The initial response to a mechanical stimulus applied to the dorsum of the paw that obstructed FWD swing was an augmentation of knee flexion and increased activity in ST and SAm. A mechanical stimulus applied to the ventral surface of the paw to obstruct BWD swing resulted in an initial conversion of hip extension to flexion and a slowing of knee flexion. There was a corresponding recruitment of SAa and RF and an enhancement of background activity in SAm. 5. The two forms of walking are differentiated by posture and limb dynamics, yet muscles participating in the basic flexor and extensor synergies are unchanged. Although central pattern generating (CPG) circuits determine the basic timing of these synergies, changes in the duration and waveform of muscle activity may depend on unique interactions among the CPG, supraspinal inputs that set posture and the animal's goal (to walk BWD or FWD) and motion-related feedback from the hindlimb. Output mutability to each muscle may depend on the balance of this tripartite input; muscles with immutable patterns may rely heavily on input from CPG circuits, whereas muscles with mutable patterns may rely more on form-specific proprioceptive and supraspinal inputs.

Adaptive control for backward quadrupedal walking. IV. Hindlimb kinetics during stance and swing.

1. Hindlimb step-cycle kinetics of forward (FWD) and backward (BWD) walking in adult cats were assessed. The hindlimb was modeled as a linked system of rigid bodies and inverse-dynamics techniques were used to calculate hip, knee, and ankle joint kinetics. For swing, net torque at each joint was divided into three components: gravitational, motion dependent, and a generalized muscle torque. For stance, vertical and horizontal components of the ground-reaction force applied at a point on the paw (center of pressure) were added to the torque calculations. Muscle torque profiles were matched to electromyograms (EMGs) recorded from hindlimb muscles. 2. Torque profiles for BWD swing were the approximate time reversal of those for FWD swing. At each joint, the net torque during swing was small because the mean motion-dependent and muscle torque components counteracted each other. At the hip a flexor muscle torque persisted except for a brief extensor muscle torque late in FWD swing and at the onset of BWD swing. At the knee the muscle torque was relatively negligible except for a peak flexor muscle torque late in FWD swing and early in BWD swing. At the ankle there was a midswing transition from a flexor to an extensor muscle torque during FWD swing and the reverse was true for BWD swing. 3. The vertical ground-reaction force was greater for the forelimbs than the hindlimbs during FWD stance; the reverse was true for BWD stance. Thus the hindlimbs bore a greater percentage (66%) of body weight than the forelimbs during BWD stance, and the forelimbs bore a greater percentage (59%) during FWD stance. For most of FWD stance, the hindlimb exerted a small propulsive ground-reaction force, but for BWD stance the hindlimb first exerted a braking force and then a propulsive force, with the transition occurring after midstance (59% of stance). 4. At the hip the ground-reaction force vector was oriented anteriorly and then posteriorly to the estimated joint center with a midstance transition during FWD stance. The muscle torque and joint power patterns showed similar transitions, changing from extensor and power generation to flexor and power absorption, respectively. For most of BWD stance the ground-reaction force vector was oriented anteriorly to the joint center and was counter-balanced by a large extensor muscle torque; nonetheless, power was absorbed because the hip flexed.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptive control for backward quadrupedal walking. III. Stumbling corrective reactions and cutaneous reflex sensitivity.

1. Four cats were trained to walk backward (BWD) and forward (FWD) on a motorized treadmill. Mechanical (taps) or electrical (pulses) stimuli were applied to the dorsal or ventral aspect of the hind paw during swing or stance. Hindlimb kinematic data, obtained by digitizing 16-mm high-speed film, were synchronized with computer-analyzed electromyograms (EMG) recorded from anterior biceps femoris (ABF), vastus lateralis (VL), lateral gastrocnemius (LG), tibialis anterior (TA), and semitendinosus (ST). Responses to taps and pulses, as well as the modulation in cutaneous reflex sensitivity to pulses, were described for both walking directions and stimulus locations. 2. After dorsal taps that obstructed FWD swing, the hindlimb initially drew back away from the obstacle with knee flexion and ST activation, ankle extension with TA suppression and LG activation, and hip extension with ABF facilitation. Next, the limb was raised over the obstacle with resumed TA activity and enhanced knee and ankle flexion, and then compensatory knee and ankle extension positioned the limb for the ensuing stance phase. 3. For ventral taps that obstructed BWD swing, the initial response also tended to draw the limb away from the obstacle with hip and ankle flexion and TA facilitation and reduced knee flexion with weak VL facilitation and suppression of ST activity. Next, ST activity resumed as knee and ankle flexion raised the limb over the obstacle, and then compensatory extension completed the swing phase for BWD walking. Thus the initial kinematic and EMG responses to obstacles were opposite for BWD versus FWD swing, and these responses were consistent with active avoidance of the obstacles. Responses during BWD walking were subtle, however, compared with those for FWD. 4. After nonobstructing taps (ventral FWD, dorsal BWD), ST and TA activation and knee and ankle flexion were coincident, demonstrating that the aforementioned differences in responses to obstructing obstacles were not simply location dependent. Regardless of the direction of walking or the location of stimulation, taps applied during stance had little immediate kinematic effect, but the subsequent swing phase was usually exaggerated, as if the response was programmed to avoid any lingering obstacle. 5. Electrical pulses did not elicit the full-blown responses typically evoked by taps. The sequencing in activation of ST and TA characteristic after laps was absent after pulses, and there were rarely dramatic kinematic responses to pulses like those easily elicited by taps. There were, in fact, few differences in responses to electrical stimulation for BWD versus FWD walking.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptive control for backward quadrupedal walking. I. Posture and hindlimb kinematics.

1. To gain new perspectives on the neural control of different forms of quadruped locomotion, we studied adaptations in posture and hindlimb kinematics for backward (BWD) walking in normal cats. Data from four animals were obtained from high-speed (100 fr/s) ciné film of BWD treadmill walking over a range of slow walking speeds (0.3-0.6 m/s) and forward (FWD) treadmill walking at 0.6 m/s. 2. Postural adaptations during BWD walking included flexion of the lumbar spine, compared to a relatively straight spine during FWD walking. The usual paw-contact sequence for FWD walking [right hindlimb (RH), right forelimb (RF), left hindlimb (LH), left forelimb (LF)] was typically reversed for BWD walking (RH, LF, LH, RF). The hindlimbs alternated consistently with a phase difference averaging 0.5 for both forms of walking, but the phasing of the forelimbs was variable during BWD walking. 3. As BWD walking speed increased from 0.3 to 0.6 m/s, average hindlimb cycle period decreased 21%, stance-phase duration decreased 29%, and stride length increased 38%. Compared to FWD walking at 0.6 m/s, stride length was 30% shorter, whereas cycle period and stance-phase duration were 17% shorter for BWD walking. For both directions, stance occupied 64 +/- 4% (mean +/- SD) of the step cycle. 4. During swing for both forms of walking, the hip, knee, and ankle joints had flexion (F) and extension (E1) phases; however, the F-E1 reversals occurred earlier at the hip and later at the knee for BWD than for FWD walking. At the ankle joint, the ranges of motion during the F and E1 phases were similar for both directions. During BWD walking, however, the knee flexed more and extended less, whereas the hip flexed less and extended more. Thus horizontal displacement of the limb resulted primarily from hip extension and knee flexion during BWD swing, but hip flexion and knee extension during FWD swing. 5. At the knee and ankle joints, there were yield (E2) and extension (E3) phases during stance for both forms of walking; however, yields at the knee and ankle joints were reduced during BWD walking. At the hip, angular motion was unidirectional, as the hip flexed during BWD stance but extended during FWD stance. Knee extension was the prime contributor to horizontal displacement of the body during BWD stance, but hip extension was the prime contributor to horizontal displacement during FWD stance. 6. Our kinematic data revealed two discriminators between BWD and FWD walking.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptive control for backward quadrupedal walking. II. Hindlimb muscle synergies.

1. To compare the basic hindlimb synergies for backward (BWD) and forward (FWD) walking, electromyograms (EMG) were recorded from selected flexor and extensor muscles of the hip, knee, and ankle joints from four cats trained to perform both forms of walking at a moderate walking speed (0.6 m/s). For each muscle, EMG measurements included burst duration, burst latencies referenced to the time of paw contact or paw off, and integrated burst amplitudes. To relate patterns of muscle activity to various phases of the step cycle, EMG records were synchronized with kinematic data obtained by digitizing high-speed ciné film. 2. Hindlimb EMG data indicate that BWD walking in the cat was characterized by reciprocal flexor and extensor synergies similar to those for FWD walking, with flexors active during swing and extensors active during stance. Although the underlying synergies were similar, temporal parameters (burst latencies and durations) and amplitude levels for specific muscles were different for BWD and FWD walking. 3. For both directions, iliopsoas (IP) and semitendinosus (ST) were active as the hip and knee joints flexed at the onset of swing. For BWD walking, IP activity decreased early, and ST activity continued as the hip extended and the knee flexed. For FWD walking, in contrast, ST activity ceased early, and IP activity continued as the hip flexed and the knee extended. For both directions, tibialis anterior (TA) was active throughout swing as the ankle flexed and then extended. A second ST burst occurred at the end of swing for FWD walking as hip flexion and knee extension slowed for paw contact. 4. For both directions, knee extensor (vastus lateralis, VL) activity began at paw contact. Ankle extensor (lateral gastrocnemius, LG) activity began during midswing for BWD walking but just before paw contact for FWD walking. At the ankle joint, flexion during the E2 phase (yield) of stance was minimal or absent for BWD walking, and ankle extension during BWD stance was accompanied by a ramp increase in LG-EMG activity. At the knee joint, the yield was also small (or absent) for BWD walking, and increased VL-EMG amplitudes were associated with the increased range of knee extension for BWD stance. 5. Although the uniarticular hip extensor (anterior biceps femoris, ABF) was active during stance for both directions, the hip flexed during BWD stance and extended during FWD stance.(ABSTRACT TRUNCATED AT 400 WORDS)