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Astronauts frequently report microgravity-induced back pain, which is generally more pronounced in the beginning of a spaceflight. The dry immersion (DI) model reproduces the early effects of microgravity in terms of global support unloading and fluid shift, both of which are involved in back pain pathogenesis. Here, we assessed spinal changes induced by exposure to 5 days of strict DI in 18 healthy men (25-43-yr old) with ( n = 9) or without ( n = 9) thigh cuffs countermeasure. Intervertebral disk (IVD) height, spinal cord position, and apparent diffusion coefficient (ADC; reflecting global water motion) were measured using magnetic resonance imaging before and after DI. After DI, IVD height increased in thoracic (+3.3 ± 0.8 mm; C 7 -T 12 ) and lumbar (+4.5 ± 0.4 mm; T 12 -L 5 ) regions but not in the cervical region (C 2 -C 7 ) of the spine. An increase in ADC after DI was observed at the L 1 (∼6% increase, from 3.2 to 3.4 × 10 -3 mm 2 /s; P < 0.001) and L 2 (∼3% increase, from 3.4 to 3.5 × 10 -3 mm 2 /s; P = 0.005) levels. There was no effect of thigh cuffs on spinal parameters. This change in IVD after DI follows the same "gradient" pattern of height increase from the cervical to the lumbar region as observed after bed rest and spaceflight. The increase in ADC at L 1 level positively correlated with reported back pain. These findings emphasize the utility of the DI model for studying early spinal changes observed in microgravity.

The aim of this study was to determine whether stimulation of sacral spinal nerve roots can induce defecation in cats. In anesthetized cats, bipolar hook electrodes were placed on the S1-S3 dorsal and/or ventral roots. Stimulus pulses (1-50 Hz, 0.2 ms) were applied to an individual S1-S3 root to induce proximal/distal colon contractions and defecation. Balloon catheters were inserted into the proximal and distal colon to measure contraction pressure. Glass marbles were inserted into the rectum to demonstrate defecation by videotaping the elimination of marbles. Stimulation of the S2 ventral root at 7 Hz induced significantly ( P < 0.05) larger contractions (32 ± 9 cmH 2 O) in both proximal and distal colon than stimulation of the S1 or S3 ventral root. Intermittent (5 times) stimulation (1 min on and 1 min off) of both dorsal and ventral S2 roots at 7 Hz produced reproducible colon contractions without fatigue, whereas continuous stimulation of 5-min duration caused significant fatigue in colon contractions. Stimulation (7 Hz) of both dorsal and ventral S2 roots together successfully induced defecation that eliminated 1 or 2 marbles from the rectum. This study indicates the possibility to develop a novel neuromodulation device to restore defecation function after spinal cord injury using a minimally invasive surgical approach to insert a lead electrode via the sacral foramen to stimulate a sacral spinal root. NEW & NOTEWORTHY This study in cats determined the optimal stimulation parameters and the spinal segment for sacral spinal root stimulation to induce colon contraction. The results have significant implications for design of a novel neuromodulation device to restore defecation function after spinal cord injury (SCI) and for optimizing sacral neuromodulation parameters to treat non-SCI people with chronic constipation.

Recent brain imaging studies have suggested that cortical remodeling within sensorimotor regions are associated with persistent low back pain and may be a driving mechanism for the impaired neuromuscular control associated with this condition. This paper outlines a new approach for investigating cortical sensorimotor integration during the performance of small-amplitude lumbopelvic movements with functional MRI. Fourteen healthy right-handed participants were instructed in the lumbopelvic movement tasks performed during fMRI acquisition. Surface electromyography (EMG) collected on 8 lumbopelvic and thigh muscles captured organized patterns of muscle activation during the movement tasks. fMRI data were collected on 10 of 14 participants. Sensorimotor cortical activation across the tasks was identified using a whole brain analysis and further explored with regional analyses of key components of the cortical sensorimotor network. Head motion had low correlation to the tasks ( r  = -0.101 to 0.004) and head translation averaged 0.98 (0.59 mm) before motion correction. Patterns of activation of the key lumbopelvic and thigh musculature (average amplitude normalized 2-17%) were significantly different across tasks ( P > 0.001). Neuroimaging demonstrated activation in key sensorimotor cortical regions that were consistent with motor planning and sensory feedback needed for performing the different tasks. This approach captures the specificity of lumbopelvic sensorimotor control using goal-based tasks (e.g., "lift your hip" vs. "contract your lumbar multifidus to 20% of maximum") performed within the confines of the scanner. Specific patterns of sensorimotor cortex activation appear to capture differences between bilateral and unilateral tasks during voluntary control of multisegmental movement in the lumbopelvic region. NEW & NOTEWORTHY We demonstrated the feasibility of using task-based functional magnetic resonance imaging (fMRI) protocols for acquiring the blood oxygen level-dependent (BOLD) response of key sensorimotor cortex regions during voluntary lumbopelvic movements. Our approach activated lumbopelvic muscles during small-amplitude movements while participants were lying supine in the scanner. Our data supports these tasks can be done with limited head motion and low correlation of head motion to the task. The approach provides opportunities for assessing the role of brain changes in persistent low back pain.

Transcutaneous spinal stimulation (TSS), a noninvasive technique to modulate sensorimotor circuitry within the spinal cord, has been shown to enable a wide range of functions that were thought to be permanently impaired in humans with spinal cord injury. However, the extent to which TSS can be used to target specific mediolateral spinal cord circuitry remains undefined. We tested the hypothesis that TSS applied unilaterally to the skin ~2 cm lateral to the midline of the lumbosacral spine selectively activates ipsilateral spinal sensorimotor circuitry, resulting in ipsilateral activation of downstream lower extremity neuromusculature. TSS cathodes and anodes were positioned lateral from the midline of the spine in 15 healthy subjects while supine, and the timing of TSS pulses was synchronized to recordings of lower extremity muscle activity and force. At motor threshold, left and right TSS-evoked muscle activity was significantly higher in the ipsilateral leg compared with contralateral recordings from the same muscles. Similarly, we observed a significant increase in force production in the ipsilateral leg compared with the contralateral leg. Delivery of paired TSS pulses, during which an initial stimulus was applied to one side of the spinal cord and 50 ms later a second stimulus was applied to the contralateral side, revealed that ipsilateral leg muscle responses decreased following the initial stimulus, whereas contralateral muscle responses did not decrease, indicating side-specific activation of lateral spinal sensorimotor circuitry. Our results indicate TSS can selectively engage ipsilateral neuromusculature via lumbosacral sensorimotor networks responsible for lower extremity function in healthy humans. NEW & NOTEWORTHY We demonstrate the selectivity of transcutaneous spinal stimulation (TSS), which has been shown to enable function in humans with chronic paralysis. Specifically, we demonstrate that TSS applied to locations lateral to the spinal cord can selectively activate ipsilateral spinal sensorimotor networks. We quantified lumbosacral spinal network activity by recording lower extremity muscle electromyography and force. Our results suggest lumbosacral TSS engages side-specific spinal sensorimotor networks associated with ipsilateral lower extremity function in humans.

We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles of the noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the defecation reflex. Colorectal motility was measured with a balloon in anesthetized rats. Electrical stimulation of the LC and A11 region increased colorectal pressure only when a GABA A receptor antagonist was injected into the lumbosacral spinal cord. The effects of the LC stimulation and A11 region stimulation on colorectal motility were inhibited by antagonists of α1-adrenoceptors and D2-like dopamine receptors injected into the lumbosacral spinal cord, respectively. Spinal injection of a norepinephrine-dopamine reuptake inhibitor augmented the colokinetic effect of LC stimulation. The effect of stimulation of each nucleus was abolished by surgical severing of the parasympathetic pelvic nerves. Our findings demonstrate that activation of descending noradrenergic neurons from the LC and descending dopaminergic neurons from the A11 region causes enhancement of colorectal motility via the lumbosacral defecation center. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers. NEW & NOTEWORTHY The present study demonstrates that electrical and chemical stimulations of the locus coeruleus or A11 region augment contractions of the colorectum. The effects of locus coeruleus and A11 stimulations on colorectal motility are due to activation of α1-adrenoceptors and D2-like dopamine receptors in the lumbosacral defecation center, respectively. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.

Microgravity-induced lumbar paraspinal muscle deconditioning may contribute to back pain commonly experienced by astronauts and may increase the risk of postflight injury. We hypothesized that a combined resistive and aerobic exercise countermeasure protocol that included spinal loading would mitigate lumbar paraspinal muscle deconditioning during 60 days of bed rest in women. Sixteen women underwent 60-day, 6° head-down-tilt bed rest (BR) and were randomized into control and exercise groups. During bed rest the control group performed no exercise. The exercise group performed supine treadmill exercise within lower body negative pressure (LBNP) for 3-4 days/wk and flywheel resistive exercise for 2-3 days/wk. Paraspinal muscle cross-sectional area (CSA) was measured using a lumbar spine MRI sequence before and after BR. In addition, isokinetic spinal flexion and extension strengths were measured before and after BR. Data are presented as means ± SD. Total lumbar paraspinal muscle CSA decreased significantly more in controls (10.9 ± 3.4%) than in exercisers (4.3 ± 3.4%; P < 0.05). The erector spinae was the primary contributor (76%) to total lumbar paraspinal muscle loss. Moreover, exercise attenuated isokinetic spinal extension loss (-4.3 ± 4.5%), compared with controls (-16.6 ± 11.2%; P < 0.05). In conclusion, LBNP treadmill and flywheel resistive exercises during simulated microgravity mitigate decrements in lumbar paraspinal muscle structure and spine function. Therefore spaceflight exercise countermeasures that attempt to reproduce spinal loads experienced on Earth may mitigate spinal deconditioning during long-duration space travel.

In people with a history of low back pain (LBP), structural and functional alterations have been observed at several peripheral and central levels of the sensorimotor pathway. These existing alterations might interact with the way the sensorimotor system responds to pain. We examined this assumption by evaluating the lumbar motor responses to experimental nociceptive input of 15 participants during remission of unilateral recurrent LBP. Quantitative T2 images (muscle functional MRI) were taken bilaterally of multifidus, erector spinae, and psoas at several segmental levels (L3 upper and L4 upper and lower endplate) and during several conditions: 1) at rest, 2) upon trunk-extension exercise without pain, and 3) upon trunk-extension exercise with experimental induced pain at the clinical pain-side (1.5-ml intramuscular hypertonic saline injections in erector spinae). Following experimental pain induction, muscle activity levels similarly reduced for all three muscles, on both painful and nonpainful sides, and at multiple segmental levels (P = 0.038). Pain intensity and localization from experimental LBP were similar as during recalled clinical LBP episodes. In conclusion, unilateral and unisegmental experimental LBP exerts a generalized and widespread decrease in lumbar muscle activity during remission of recurrent LBP. This muscle response is consistent with previous observed patterns in healthy people subjected to the same experimental pain paradigm. It is striking that similar inhibitory patterns in response to pain could be observed, despite the presence of preexisting alterations in the lumbar musculature during remission of recurrent LBP. These results suggest that motor output can modify along the course of recurrent LBP., (Copyright © 2016 the American Physiological Society.)

Context-specific adaptation (Shelhamer M, Clendaniel R. Neurosci Lett 332: 200-204, 2002) explains that reflexive responses can be maintained with different "calibrations" for different situations (contexts). Which context cues are crucial and how they combine to evoke context-specific adaptation is not fully understood. Gaze stabilization in birds is a nice model with which to tackle that question. Previous data showed that when pigeons (Columba livia) were hung in a harness and subjected to a frontal airstream provoking a flying posture ("flying condition"), the working range of the optokinetic head response [optocollic reflex (OCR)] extended toward higher velocities compared with the "resting condition." The present study was aimed at identifying which context cues are instrumental in recalibrating the OCR. We investigated that question by using vibrating stimuli delivered during the OCR provoked by rotating the visual surroundings at different velocities. The OCR gain increase and the boost of the fast phase velocity observed during the "flying condition" were mimicked by body vibration. On the other hand, the newly emerged relationship between the fast-phase and slow-phase velocities in the "flying condition" was mimicked by head vibration. Spinal cord lesion at the lumbosacral level decreased the effects of body vibration, whereas lesions of the lumbosacral apparatus had no effect. Our data suggest a major role of muscular proprioception in the context-specific adaptation of the stabilizing behavior, while the vestibular system could contribute to the context-specific adaptation of the orienting behavior. Participation of an efferent copy of the motor command driving the flight cannot be excluded.

As part of the nutrition-countermeasures (NUC) study in Cologne, Germany in 2010, seven healthy male subjects underwent 21 days of head-down tilt bed rest and returned 153 days later to undergo a second bout of 21-day bed rest. As part of this model, we aimed to examine the recovery of the lumbar intervertebral discs and muscle cross-sectional area (CSA) after bed rest using magnetic resonance imaging and conduct a pilot study on the effects of bed rest in lumbar muscle activation, as measured by signal intensity changes in T(2)-weighted images after a standardized isometric spinal extension loading task. The changes in intervertebral disc volume, anterior and posterior disc height, and intervertebral length seen after bed rest did not return to prebed-rest values 153 days later. While recovery of muscle CSA occurred after bed rest, increases (P ≤ 0.016) in multifidus, psoas, and quadratus lumborum muscle CSA were seen 153 days after bed rest. A trend was seen for greater activation of the erector spinae and multifidus muscles in the standardized loading task after bed rest. Greater reductions of multifidus and psoas CSA muscle and greater increases in multifidus signal intensity with loading were associated with incidence of low back pain in the first 28 days after bed rest (P ≤ 0.044). The current study contributes to our understanding of the recovery of the lumbar spine after 21-day bed rest, and the main finding was that a decrease in spinal extensor muscle CSA recovers within 5 mo after bed rest but that changes in the intervertebral discs persist.

Vasomotor control by the sympathetic nervous system presents substantial heterogeneity within different tissues, providing appropriate homeostatic responses to maintain basal/stimulated cardiovascular function both at normal and pathological conditions. The availability of a reproducible technique for simultaneous measurement of sympathetic drive to different tissues is of great interest to uncover regional patterns of sympathetic nerve activity (SNA). We propose the association of tyrosine hydroxylase immunoreactivity (THir) with image analysis to quantify norepinephrine (NE) content within nerve terminals in arteries/arterioles as a good index for regional sympathetic outflow. THir was measured in fixed arterioles of kidney, heart, and skeletal muscle of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (123 ± 2 and 181 ± 4 mmHg, 300 ± 8 and 352 ± 8 beats/min, respectively). There was a differential THir distribution in both groups: higher THir was observed in the kidney and skeletal muscle (∼3-4-fold vs. heart arterioles) of WKY; in SHR, THir was increased in the kidney and heart (2.4- and 5.3-fold vs. WKY, respectively) with no change in the skeletal muscle arterioles. Observed THir changes were confirmed by either: 1) determination of NE content (high-performance liquid chromatography) in fresh tissues (SHR vs. WKY): +34% and +17% in kidney and heart, respectively, with no change in the skeletal muscle; 2) direct recording of renal (RSNA) and lumbar SNA (LSNA) in anesthetized rats, showing increased RSNA but unchanged LSNA in SHR vs. WKY. THir in skeletal muscle arterioles, NE content in femoral artery, and LSNA were simultaneously reduced by exercise training in the WKY group. Results indicate that THir is a valuable technique to simultaneously evaluate regional patterns of sympathetic activity.

This study compared the baroreflex control of lumbar and renal sympathetic nerve activity (SNA) in conscious rats. Arterial pressure (AP) and lumbar and renal SNA were simultaneously recorded in six freely behaving rats. Pharmacological estimates of lumbar and renal sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was significantly (P < 0.05) lower for lumbar [3.0 +/- 0.4 normalized units (NU)/mmHg] than for renal (7.6 +/- 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar and renal BRS were continuously assessed by computing the gain of the transfer function relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer gain was considered only when coherence between AP and SNA significantly differed from zero, which was verified in 99 +/- 1 and 96 +/- 3% of cases for lumbar and renal SNA, respectively. When averaged over the entire baseline period, spontaneous BRS was significantly (P < 0.05) lower for lumbar (1.3 +/- 0.2 NU/mmHg) than for renal (2.3 +/- 0.3 NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation coefficients were 26 +/- 2 and 28 +/- 2% for lumbar and renal SNA, respectively). These fluctuations were positively correlated in five of six rats (R = 0.44 +/- 0.06; n = 204 +/- 8; P < 0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA shows quantitative differences but is modulated in a mostly coordinated way.

The mechanical properties of motor units have been extensively studied under isometric conditions. Under dynamic conditions, the relationship between the force developed by single motor units and the muscle shortening velocity was determined for relatively high frequencies of activation. However, the interaction between the force-shortening velocity relation and the force-rate of activation relation was still unknown. We studied the power (which is the product of force and velocity) developed by single or groups of motor units during sinusoidal muscle stretches of 1-, 2-, 4-, 6-, and 8-Hz frequency. Motor units were stimulated with frequencies of 20, 40, 60, 80, 100, and 120 Hz during the shortening phase of the muscle stretch. The relationships, for different shortening velocities, between the power developed by single or groups of motor units and the frequency of stimulation were sigmoidal. However, these relations were not proportional to the shortening velocity. The relationships, for different frequencies of stimulation, between the power and the shortening velocity exhibited a maximum. The shortening velocity at which this maximum occurred increased with the frequency of stimulation. Slow motor units showed the lowest of those shortening velocities, whereas the fast fatigable motor units showed the highest. Groups of slow (or fast fatigue resistant) motor units had similar shortening velocities to those of single slow (or fast fatigue resistant) motor units. A mathematical function was fitted, using regression analysis, for all single and groups of motor units to the relationship among the power, the shortening velocity, and the frequency of activation. This function allowed examination, for different shortening velocity-frequency of activation combinations, of the relationship between the power developed by single and groups of motor units and the maximal isometric tetanic force they developed. These relationships were usually not monotonic but a monotonic relation could be obtained if slow, fast resistant, and fast fatigable motor units were activated at different frequencies. These results suggest that during a movement, the frequency of activation of motor units is mainly adjusted to the movement velocity and that the power developed by a muscle is mainly adjusted by the number of recruited motor units.

In the appendicular skeleton, substantial evidence demonstrates that somatosensory input from deep tissues including limb muscles and joints elicits somatosympathetic reflexes. Much less is known about the presence and organization of these reflexes from the axial skeleton. We determined if mechanical loading of the lumbar spine and lumbar paraspinal muscle irritation reflexively affects postganglionic sympathetic nerve discharge (SND) to the spleen and kidney. In 27 alpha-chloralose-anesthetized cats, the L2-4 multifidus muscles were injected with the inflammatory irritant mustard oil (20%, 60 microl total) and a vertebral load (100% body weight) was applied dorsal-ventral at the L3 spinous process. Mustard oil injection alone without vertebral loading (n = 7) increased mean splenic SND (60%), renal SND (30%), and heart rate (HR; 52 bpm). Mustard oil injection accompanied by the vertebral load (n = 7) increased mean splenic SND (55%), renal SND (16%), and HR (27 bpm). Blood pressure changes were biphasic and could not account for these changes. When the vertebral load accompanied mustard oil, the increases in splenic SND, renal SND, and HR remained elevated in a pattern significantly different from when the vertebral load was absent. Vehicle injection combined with the mechanical load (n = 3) did not change any of the autonomic responses. Similarly, mustard oil injection combined with a mechanical load did not change these responses when either the medial branches of the dorsal rami from T11-L5 had been cut (n = 4) or when the spinal cord had been transected between the second and third cervical vertebrae (n = 6). The results indicate that inflammatory stimulation of multifidus muscle in the low back evokes a somatosympathetic reflex integrated supraspinally in the upper cervical spinal cord or higher. The reflex's afferent arm travels in the medial branch of the dorsal ramus, and its efferent arm can affect sympathetic outflow to the spleen and the kidney as well as HR and BP. A static mechanical load applied to the lumbar spine accompanying the inflammatory stimulus appears to sustain the inflammatory-induced reflex activity.

The rhythmogenic capacity of the tail-innervating segments (L4-Co3) of the spinal cord was studied in isolated spinal cord and tail-spinal cord preparations of neonatal rats. Bath-applied serotonin/N-methyl-D-aspartate (NMDA) failed to produce a robust sacrococcygeal rhythmicity following midlumbar transection of the spinal cord. By contrast, a regular alternating left-right rhythm could be induced in the sacrococcygeal segments by application of noradrenaline (NA) or NA and NMDA before and after midlumbar transection of the cord. This rhythm was accelerated with the concentration of NMDA and was blocked by alpha1 or alpha2 adrenoceptor antagonists. The efferent bursts induced by NA/NMDA were accompanied by rhythmic tail movements produced by alternating activation of the left and right tail muscles and by coactivation of flexors, extensors, and abductors on a given side of the tail. This coactivation implies that reciprocal inhibitory pathways were not activated during the rhythm. Lesion experiments revealed that the rhythmogenic circuitry is distributed along all or most of the sacrococcygeal segments. The NA/NMDA-induced rhythm persisted in the isolated sacrococcygeal (S1-Co3), sacral (S1-S4), coccygeal (Co1-Co3), and smaller isolated regions of the sacrococcygeal cord. The rhythm also could be maintained in longitudinally split sacrococcygeal hemicords in which flexor, extensor, and abductor motoneurons are coactivated. This finding indicates that neither left/right nor flexor/extensor inhibitory interactions are required for rhythmogenesis in the sacrococcygeal cord. A slow rhythm lacking the alternating left-right pattern was induced by NA/NMDA in tail-innervating caudal lumbar segments of isolated L4-Co3 preparations. This rhythm was independent of the concurrent sacrococcygeal rhythm and the activity pattern of the tail musculature and it does not seem to contribute to rhythmic tail movements under these conditions. Comparative studies of the rhythm produced in the isolated caudal lumbar, sacrococcygeal cord, and caudal thoracic-rostral lumbar segments revealed that the S1-Co3 rhythm was faster than the L4-L6 pattern and slower than the T6-L3 rhythm. It is suggested that the caudal lumbar and sacrococcygeal segments of the cord are normally driven by the faster rostral lumbar central pattern generators. The relevance of the findings described above to pattern generation in the mammalian spinal cord is discussed.

We examined the ability of the isolated lumbosacral spinal cord of the neonatal mouse (P0-7) to generate rhythmic motor activity under several different conditions. In the absence of electrical or pharmacological stimulation, we recorded several patterns of spontaneous ventral root depolarization and discharge. Spontaneous, alternating discharge between contralateral ventral roots could occur two to three times over a 10-min interval. We also observed other patterns, including left-right synchrony and rhythmic activity restricted to one side of the cord. Trains of stimuli delivered to the lumbar/coccygeal dorsal roots or the sural nerve reliably evoked episodes of rhythmic activity. During these evoked episodes, rhythmic ventral root discharges could occur on one side of the cord or could alternate from side to side. Bath application of a combination of N-methyl-D,L-aspartate (NMA), serotonin, and dopamine produced rhythmic activity that could last for several hours. Under these conditions, the discharge recorded from the left and right L(1)-L(3) ventral roots alternated. In the L(4)-L(5) segments, the discharge had two peaks in each cycle, coincident with discharge of the ipsilateral and contralateral L(1)-L(3) roots. The L(6) ventral root discharge alternated with that recorded from the ipsilateral L(1)-L(3) roots. We established that the drug-induced rhythm was locomotor-like by recording an alternating pattern of discharge between ipsilateral flexor and extensor hindlimb muscle nerves. In addition, by recording simultaneously from ventral roots and muscle nerves, we established that ankle flexor discharge was in phase with ipsilateral L(1)/L(2) ventral root discharge, while extensor discharge was in phase with ipsilateral L(6) ventral root discharge. Rhythmic patterns of ventral root discharge were preserved following mid-sagittal section of the spinal cord, demonstrating that reciprocal inhibitory connections between the left and right sides of the cord are not essential for rhythmogenesis in the neonatal mouse cord. Blocking N-methyl-D-aspartate receptors, in both the intact and the hemisected preparation, revealed that these receptors contribute to but are not essential for rhythmogenesis. In contrast, the rhythm was abolished following blockade of kainate/AMPA receptors with 6-cyano-7-nitroquinoxalene-2,3-dione. These findings demonstrate that the isolated mouse spinal cord can produce a variety of coordinated activities, including locomotor-like activity. The ability to study these behaviors under a variety of different conditions offers promise for future studies of rhythmogenic mechanisms in this preparation.

Studies suggest that the human lumbosacral spinal cord can generate steplike oscillating electromyographic (EMG) patterns, but it remains unclear to what degree these efferent patterns depend on the phasic peripheral sensory information associated with bilateral limb movements and loading. We examined the role of sensory information related to lower-extremity weight bearing in modulating the efferent motor patterns of spinal-cord-injured (SCI) subjects during manually assisted stepping on a treadmill. Four nonambulatory subjects, each with a chronic thoracic spinal cord injury, and two nondisabled subjects were studied. The level of loading, EMG patterns, and kinematics of the lower limbs were studied during manually assisted or unassisted stepping on a treadmill with body weight support. The relationships among lumbosacral motor pool activity [soleus (SOL), medial gastrocnemius (MG), and tibialis anterior (TA)], limb load, muscle-tendon length, and velocity of muscle-tendon length change were examined. The EMG mean amplitude of the SOL, MG, and TA was directly related to the peak load per step on the lower limb during locomotion. The effects on the EMG amplitude were qualitatively similar in subjects with normal, partial, or no detectable supraspinal input. Responses were most consistent in the SOL and MG at load levels of < 50% of a subject's body weight. The modulation of the EMG amplitude from the SOL and MG, both across steps and within a step, was more closely associated with limb peak load than muscle-tendon stretch or the velocity of muscle-tendon stretch. Thus stretch reflexes were not the sole source of the phasic EMG activity in flexors and extensors during manually assisted stepping in SCI subjects. The EMG amplitude within a step was highly dependent on the phase of the step cycle regardless of level of load. These data suggest that level of loading on the lower limbs provides cues that enable the human lumbosacral spinal cord to modulate efferent output in a manner that may facilitate the generation of stepping. These data provide a rationale for gait rehabilitation strategies that utilize the level of load-bearing stepping to enhance the locomotor capability of SCI subjects.