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Highly varying patterns of electrostimulation (Dynamic Stimulation, DS) delivered to the dorsal cord through an epidural array with 18 independent electrodes transiently facilitate corticospinal motor responses, even after spinal injury. To partly unravel how corticospinal input are affected by DS, we introduced a corticospinal platform that allows selective cortical stimulation during the multisite acquisition of cord dorsum potentials (CDPs) and the simultaneous supply of DS. Firstly, the epidural interface was validated by the acquisition of the classical multisite distribution of CDPs and their input-output profile elicited by pulses delivered to peripheral nerves. Apart from increased EMGs, DS selectively increased excitability of the spinal interneurons that first process corticospinal input, without changing the magnitude of commands descending from the motor cortex, suggesting a novel correlation between muscle recruitment and components of cortically-evoked CDPs. Finally, DS increases excitability of post-synaptic spinal interneurons at the stimulation site and their responsiveness to any residual supraspinal control, thus supporting the use of electrical neuromodulation whenever the motor output is jeopardized by a weak volitional input, due to a partial disconnection from supraspinal structures and/or neuronal brain dysfunctions., Competing Interests: Declaration of Competing Interest VRE, a researcher on the study team holds shareholder interest in Onward and holds certain inventorship rights on intellectual property licensed by The Regents of the University of California to Onward. VRE, and PG, researchers on the study team hold shareholder interest in SpineX Inc. PG is an employee of SpineX Inc. WL holds shareholder interest in Aneuvo as well as inventorship of IPs licensed by The Regents of the University of California to Aneuvo., (Copyright © 2023. Published by Elsevier Inc.)

The present review focuses on the physiological states of spinal networks, which are stochastically modulated by continuously changing ensembles of proprioceptive and supraspinal input resulting in highly redundant neural networks. Spinal epidural interfaces provide a platform for probing spinal network dynamics and connectivity among multiple motor pool-specific spinal networks post-injury under in vivo experimental conditions. Continuous epidural low-frequency pulses at low intensity can evoke motor responses of stochastically changing amplitudes and with an oscillatory pattern of modulation. The physiological significance of this oscillatory pattern, intrinsic to "resting" spinal networks and observed in both uninjured and injured locomotor circuits, is unclear. This neural variability among spinal networks appears to be a fundamental mechanism of the network's design and not a "noise" interfering with movement control. Data to date also suggest that the greater the level of stimulation above motor threshold, the greater the loss of modulation over the motor output that is physiologically provided by interneuronal networks, which integrate naturally occurring proprioceptive and cutaneous input generated during movement. Sub-motor threshold spinal electrical stimulation experiments demonstrate a range of functional improvements of multiple physiological systems when used in concert with sensorimotor training after spinal cord injury. Although our understanding of the systemic, cellular and molecular modulatory mechanisms that trigger these activity-dependent adaptive processes remain incomplete, some basic physiological principles have evolved, at least at the systemic and neural network levels and to some degree at the cellular level., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Epidural electrical spinal stimulation can facilitate recovery of volitional motor control in individuals that have been completely paralyzed for more than a year. We recently reported a novel neuromodulation method named Dynamic Stimulation (DS), which short-lastingly increased spinal excitability and generated a robust modulation of locomotor networks in fully-anesthetized intact adult rats. In the present study, we applied repetitive DS patterns to four lumbosacral segments acutely after a contusive injury at lumbar level. Repetitive DS delivery restored the spinally-evoked motor EMG responses that were previously suppressed by a calibrated spinal cord contusion. Sham experiments without DS delivery did not allow any spontaneous recovery. Thus, DS uniquely provides the potential for a greater long-term functional recovery after paralysis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the thoracolumbar spine in neurologically intact rhesus macaques can activate the LUT, including activation of the bladder detrusor muscle, the urethral sphincter and pelvic floor muscles. Urodynamic studies show improved voiding efficiency and decreased post-voiding residual volumes in the bladder, while maintaining coordinated activity in the detrusor and sphincter with physiologic detrusor peak pressure, contraction duration, and urine flow rate remaining unchanged. We conclude that TSCS may represent a novel approach to activate the LUT and enable voiding in select neurological conditions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Olfactory ensheathing cells (OECs) are unique glia that support axon outgrowth in the olfactory system, and when used as cellular therapy after spinal cord injury, improve recovery and axon regeneration. Here we assessed the effects of combining OEC transplantation with another promising therapy, epidural electrical stimulation during a rehabilitative motor task. Sprague-Dawley rats received a mid-thoracic transection and transplantation of OECs or fibroblasts (FBs) followed by lumbar stimulation while climbing an inclined grid. We injected pseudorabies virus (PRV) into hindlimb muscles 7 months post-injury to assess connectivity across the transection. Analyses showed that the number of serotonergic (5-HT) axons that crossed the rostral scar border and the area of neurofilament-positive axons in the injury site were both greater in OEC- than FB-treated rats. We detected PRV-labeled cells rostral to the transection and remarkable evidence of 5-HT and PRV axons crossing the injury site in 1 OEC- and 1 FB-treated rat. The axons that crossed suggested either axon regeneration (OEC) or small areas of probable tissue sparing (FB). Most PRV-labeled thoracic neurons were detected in laminae VII or X, and ~25% expressed Chx10, a marker for V2a interneurons. These findings suggest potential regeneration or sparing of circuits that connect thoracic interneurons to lumbar somatic motor neurons. Despite evidence of axonal connectivity, no behavioral changes were detected in this small-scale study. Together these data suggest that when supplemented with epidural stimulation and climbing, OEC transplantation can increase axonal growth across the injury site and may promote recovery of propriospinal circuitry., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6- C8+ and C6+ C8-) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6- Ref+ and C8- Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner., (Copyright © 2016. Published by Elsevier Inc.)

The corticospinal and rubrospinal tracts are the predominant tracts for controlling skilled hand function. Injuries to these tracts impair grasping but not gross motor functions such as overground locomotion. The aim of the present study was to determine whether or not, after damage to both the corticospinal and rubrospinal tracts, other spared subcortical motor pathway can mediate the recovery of skilled hand function. Adult rats received a bilateral injury to the corticospinal tract at the level of the medullar pyramids and a bilateral ablation of the rubrospinal axons at C4. One group of rats received, acutely after injury, two injections of chondroitinase-ABC at C7, and starting at 7days post-injury were enrolled in daily reaching and grasping rehabilitation (CHASE group, n=5). A second group of rats received analogous injections of ubiquitous penicillinase, and did not undergo rehabilitation (PEN group, n=5). Compared to rats in the PEN group, CHASE rats gradually recovered the ability to reach and grasp over 42days after injury. Overground locomotion was mildly affected after injury and both groups followed similar recovery. Since the reticulospinal tract plays a predominant role in motor control, we further investigated whether or not plasticity of this pathway could contribute to the animal's recovery. Reticulospinal axons were anterogradely traced in both groups of rats. The density of reticulospinal processes in both the normal and ectopic areas of the grey ventral matter of the caudal segments of the cervical spinal cord was greater in the CHASE than PEN group. The results indicate that after damage to spinal tracts that normally mediate the control of reaching and grasping in rats other complementary spinal tracts can acquire the role of those damaged tracts and promote task-specific recovery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In this review we use the term spasticity to mean the generation of abnormal patterns of forces that are generated involuntarily. It is clear that spasticity can have both detrimental and beneficial effects on the neuromuscular system of the affected individuals. Muscle spasticity routinely occurs after a spinal cord injury and other neurological disorders. Although often studied as if there was a single mechanism associated with this phenomenon, it is clear that there are multiple mechanisms having both neural and muscular components, particularly when such terms also are applied to other neuromotor disorders. The aims of this review are to describe the neural and muscular adaptations that are associated with spasticity, highlight the major possible mechanisms producing spasticity, and discuss the role of selected pharmacological interventions in controlling spasticity. Spasticity appears to be related to altered membrane channel and receptor properties that are primarily associated with an increase in the excitability of spinal neurons, resulting in abnormal (in the intensity and combination of muscles activated) contractions that are generated involuntarily. While most of the efforts to understand the etiology of spasticity have focused on motoneurons, it is likely that spinal interneurons play a central role as well as the mechanical properties of muscle fibers and associated connective tissues. A number of pharmacological interventions have been used in attempts to suppress spasticity with varying results, but concomitant with suppressed muscle activation, there can be significant side effects including a reduction in the control of movement., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Spinal Wistar Hannover rats injected with olfactory ensheathing glia (OEG) have been shown to recover some bipedal stepping and climbing abilities. Given the intrinsic ability of the spinal cord to regain stepping with pharmacological agents or epidural stimulation after a complete mid-thoracic transection, we asked if functional recovery after OEG injections is due to changes in the caudal stump or facilitation of functional regeneration of axons across the transection site. OEG were injected rostral and caudal to the transection site immediately after transection. Robotically assisted step training in the presence of intrathecal injections of a 5-HT(2A) receptor agonist (quipazine) was used to facilitate recovery of stepping. Bipedal stepping as well as climbing abilities were tested over a 6-month period post-transection to determine any improvement in hindlimb functional due to OEG injections and/or step training. The ability for OEG to facilitate regeneration was analyzed electrophysiologically by transcranially stimulating the brainstem and recording motor evoked potentials (MEP) with chronically implanted intramuscular EMG electrodes in the soleus and tibalis anterior with and without intrathecal injections of noradrenergic, serotonergic, and glycinergic receptor antagonists. Analyses confirmed that along with improved stepping ability and increased use of the hindlimbs during climbing, only OEG rats showed recovery of MEP. In addition the MEP signals were eliminated after a re-transection of the spinal cord rostral to the original transection and were modified in the presence of receptor antagonists. These data indicate that improved hindlimb function after a complete transection was coupled with OEG-facilitated functional regeneration of axons. This article is part of a Special Issue entitled: Understanding olfactory ensheathing glia and their prospect for nervous system repair., (Published by Elsevier Inc.)

The effects of peripheral nerve grafts (PNG) and acidic fibroblast growth factor (alpha FGF) combined with step training on the locomotor performance of complete spinal cord-transected (ST, T8) adult rats were studied. Rats were assigned randomly to five groups (N=10 per group): sham control (laminectomy only), ST only, ST-step-trained, repaired (ST with PNG and alpha FGF treatment), or repaired-step-trained. Step-trained rats were stepped bipedally on a treadmill 20 min/day, 5 days/week for 6 months. Bipolar intramuscular EMG electrodes were implanted in the soleus and tibialis anterior (TA) muscles of ST-step-trained (n=3) and repaired-step-trained (n=2) rats. Gait analysis was conducted at 3 and 6 months after surgery. Stepping analysis was completed on the best continuous 10-s period of stepping performed in a 2-min trial. Significantly better stepping (number of steps, stance duration, swing duration, maximum step length, and maximum step height) was observed in the repaired and repaired-step-trained than in the ST and ST-step-trained rats. Mean EMG amplitudes in both the soleus and TA were significantly higher and the patterns of activation of flexors and extensors more reciprocal in the repaired-step-trained than ST-step-trained rats. 5-HT fibers were present in the lumbar area of repaired but not ST rats. Thus, PNG plus alpha FGF treatment resulted in a clear improvement in locomotor performance with or without step training. Furthermore, the number of 5-HT fibers observed below the lesion was related directly to stepping performance. These observations indicate that the improved stepping performance in Repaired rats may be due to newly formed supraspinal control via regeneration., ((c) 2010 Elsevier Inc. All rights reserved.)

Although epidural stimulation is a technique that has been used for a number of years to treat individuals with a spinal cord injury, the intended outcome has been to suppress plasticity and pain. Over the last decade considerable progress has been made in realizing the potential of epidural stimulation to facilitate posture and locomotion in subjects with severe spinal cord injury who lack the ability to stand or to step. This progress has resulted primarily from experiments with mice, rats and cats having a complete spinal cord transection at a mid-thoracic level and in humans with a complete spinal cord injury. This review describes some of these experiments performed after the complete elimination of supraspinal input that demonstrates that the circuitry necessary to control remarkably normal locomotion appears to reside within the lumbosacral region of the spinal cord. These experiments, however, also demonstrate the essential role of processing proprioceptive information associated with weight-bearing stepping or standing by the spinal circuitry. For example, relatively simple tonic signals provided to the dorsum of the spinal cord epidurally can result in complex and highly adaptive locomotor patterns. Experiments emphasizing a significant complementary effect of epidural stimulation when combined with pharmacological facilitation, e.g., serotonergic agonists, and/or chronic step training also are described. Finally, a major point emphasized in this review is the striking similarity of the lumbosacral circuitry controlling locomotion in the rat and in the human.

L1 is a cell adhesion molecule associated with axonal outgrowth, fasciculation, and guidance during development and injury. In this study, we examined the long-term effects of spinal cord injury with and without exercise on the re-expression of L1 throughout the rat spinal cord. Spinal cords from control rats were compared to those from rats receiving complete mid-thoracic spinal cord transections at postnatal day 5, daily treadmill step training for up to 8 weeks, or both transection and step training. Three months after spinal cord transection, we observed substantially higher levels of L1 expression by both Western blot analysis and immunocytochemistry in rats with and without step training. Higher expression levels of L1 were seen in the dorsal gray matter and in the dorsal lateral funiculus both above and below the lesion site. In addition, L1 was re-expressed on the descending fibers of the corticospinal tract above the lesion. L1-labeled axons also expressed GAP-43, a protein associated with axon outgrowth and regeneration. Treadmill step training had no effect on L1 expression in either control or transected rats despite the fact that spinal transected rats displayed improved stepping patterns indicative of spinal learning. Thus, spinal cord transection at an early age induced substantial L1 expression on axons near the lesion site, but was not additionally augmented by exercise.

We have conducted studies to determine the potential of exercise to benefit the injured spinal cord using neurotrophins. Adult rats were randomly assigned to one of three groups: (1) intact control (Con); (2) sedentary, hemisected at a mid-thoracic level (Sed-Hx), or (3) exercised, hemisected (Ex-Hx). One week after surgery, the Ex-Hx rats were exposed to voluntary running wheels for 3, 7, or 28 days. BDNF mRNA levels on the lesioned side of the spinal cord lumbar region of Sed-Hx rats were approximately 80% of Con values at all time points and BDNF protein levels were approximately 40% of Con at 28 days. Exercise compensated for the reductions in BDNF after hemisection, such that BDNF mRNA levels in the Ex-Hx rats were similar to Con after 3 days and higher than Con after 7 (17%) and 28 (27%) days of exercise. After 28 days of exercise, BDNF protein levels were 33% higher in Ex-Hx than Con rats and were highly correlated (r=0.86) to running distance. The levels of the downstream effectors for the action of BDNF on synaptic plasticity synapsin I and CREB were lower in Sed-Hx than Con rats at all time points. Synapsin I mRNA and protein levels were higher in Ex-Hx rats than Sed-Hx rats and similar to Con rats at 28 days. CREB mRNA values were higher in Ex-Hx than Sed-Hx rats at all time points. Hemisection had no significant effects on the levels of NT-3 mRNA or protein; however, voluntary exercise resulted in an increase in NT-3 mRNA levels after 28 days (145%). These results are consistent with the concept that synaptic pathways under the regulatory role of BDNF induced by exercise can play a role in facilitating recovery of locomotion following spinal cord injury.

Hind limb suspension is a model frequently utilized to study muscle plasticity. One reason for its frequent use is that it is thought to mimic in many respects the conditions imposed on some muscles during spaceflight. Changes in muscle properties that follow hind limb suspension generally have been attributed to reductions in the recruitment of these muscles. To determine the validity of this assumption, the electromyographic (EMG) activity of three hind limb muscles, the soleus, a slow extensor, the medial gastrocnemius, a fast extensor, and the tibialis anterior, a fast flexor, was studied. The EMG was recorded in each rat for 25 min of each hour for 24 consecutive hours, 7 and 3 days prior, on the day of, and 3, 7, 14, 21, and 28 days after hind limb suspension. Control rats were treated similarly and their EMG recorded on corresponding days. Compared with presuspension, soleus activity was reduced significantly to 91% on the first day of suspension, but had recovered to 81% of its normal activity by the seventh day. Similarly, there was a significant reduction to 54% in activity of the medial gastrocnemius on the day of hind limb suspension which recovered to 98% of its presuspension values by day 7. In contrast, the tibialis anterior showed a significant increase in activity relative to presuspension values within 3 days of the initiation of suspension. These data indicate that hind limb suspension produced only a relatively short-term reduction in the activity of both the soleus and medial gastrocnemius and results in an increased activity in the tibialis anterior. Collaborative studies showed that significant alterations in muscle mass and metabolic and mechanical properties occurred and persisted in spite of the recovery of activation in the soleus and medial gastrocnemius. In addition, no alterations in mass and mechanical properties were evident in the tibialis anterior during a 4-week suspension even though the EMG increased after hind limb suspension. Together, these data indicate that the adaptations in muscle properties following hind limb suspension are not closely related to changes in the total amount of muscle EMG activity per day.

The existence of "concomitant" (coexistent) electromyographic reflex responses in soleus and tibialis anterior muscles, produced by posterior tibial nerve stimulation, has been cited as evidence for "reciprocal excitation" between these antagonistic muscles normally reflexly linked by reciprocal inhibition. Using the Hoffmann reflex procedure and posterior tibial nerve stimulation, the existence of true reciprocal excitation was tested in six subjects with no neuromuscular impairment. Coexistent EMG responses were observed in all subjects. In no instance, however, could the tibialis anterior EMG volley to posterior tibial nerve stimulation of the soleus muscle be antidromically blocked by common peroneal nerve stimulation applied at 10 to 20 ms offset latencies. A second stimulation pulse applied to the common peroneal nerve at similar offset latencies did antidromically block a tibialis anterior reflex response to common peroneal nerve stimulation. Therefore, volume conduction of reflex activity from the posterior tibial compartment to the anterior tibial compartment was a common observance. We suggest that coexistent EMG reflex responses, presumed to reflect reciprocal excitation, should be tested by the procedure described to reject the possibility of EMG cross-talk as a confounding variable or as the actual variable under investigation.

The effects of ambulatory training on the extent and time course of recovery of weight-bearing-stepping in cats spinalized (T12-T13) as adults were investigated. One month after spinal cord transection, 14 of 16 cats were capable of bearing the full weight of their hindquarters with their hind limbs during stepping on a motor-driven treadmill if the tail was pinched or crimped. Of those 14 cats 8 were assigned to a trained and 6 to an untrained group. Trained cats were subjected to 30 min/day of treadmill exercise, 5 days/week. Training was initiated 1 month posttransection and continued until 5 to 7 months posttransection. Daily records were kept on the treadmill speeds used, the time at each speed, and the number of steps that were not full weight bearing. The number of full-weight-bearing steps times treadmill speed was used as a measure of performance. The tail was crimped whenever necessary, but was required less and less as training progressed. Performance plateaus were reached between 25 and 85 days after initiating training (mean = 48 +/- 22 days). Maximum treadmill speeds increased in untrained cats from 0.075 +/- 0.042 m/s 1 month posttransection to 0.240 +/- 0.042 m/s 5 to 7 months posttransection and those of trained cats increased from 0.079 +/- 0.045 m/s to 0.619 +/- 0.133 m/s during this same period. We conclude that a much larger proportion of adult spinal cats are capable of full-weight-bearing stepping than reported, and that training which emphasizes early tail crimping and complete weight bearing at all times results in marked improvements in the locomotor capacity of the hind limbs.

Effects of low thoracic spinal transection on muscle weights, fiber type distributions, and fiber cross-sectional areas (CSAs) of selected cat hind limb mixed-fast flexors and extensors and slow extensors were studied. Cats were spinalized at T12 at 2 weeks of age and maintained for 6 to 12 months. In general spinalization resulted in a decrease in muscle weights of extensors, while the weights of those muscles that function as either flexors or as both flexors and extensors were maintained. The percentages of fast-twitch [fast glycolytic (FG) and fast oxidative-glycolytic (FOG)] fibers increased and slow oxidative (SO) fibers decreased as a result of spinalization. However, FG fibers had a smaller CSA after spinal transection in both extensors and flexors. The total relative CSA of FG fibers per whole muscle was similar in spinalized and control cats. The relative muscle CSA occupied by SO fibers decreased in extensors and flexors as a result of a lower proportion of SO fibers and/or smaller SO fibers in spinalized cats. These findings suggest that muscles become more "fast-like" histochemically while little change occurs in the oxidative staining properties in either extensors or flexors in 6- to 12-month-old cats transected at 2 weeks of age. Further, these data suggest that the amount of muscle atrophy that occurs as a result of spinal transection is not closely related to the percentage reduction in SO fibers.

Hindlimb suspension (HS) is a ground-based simulation model for spaceflight commonly used to study the effects of unloading on skeletal muscle. The purpose of the present study was to determine the effects of a daily short-duration, high-load exercise training program in ameliorating the atrophic response and associated adaptations in the mechanical properties of the soleus (SOL) and medial gastrocnemius (MG) muscles to HS. Male Sprague-Dawley rats (mean body weight, approximately 250 g) were assigned randomly to one of three groups: control (CON, n = 7), HS, (n = 7), and HS plus exercise (HS-EX, n = 8). The exercise consisted of rats climbing up a 1-m grid inclined at approximately 85 degrees for eight repetitions with a load equal to 75% body weight attached to their tails repeated four times daily during their active period. Following 7 days, soleus wet weights in the HS and HS-EX rats were 42 and 23% lower than those in the CON rats. The SOL muscle weight to body weight ratio in the HS group was 32% smaller than that in the CON group, whereas it was similar to that of CON in the HS-EX. Maximum tetanic tensions in the HS and HS-EX groups were 44 and 27% less than that in CON, with that in HS-EX being significantly greater than that in HS.(ABSTRACT TRUNCATED AT 250 WORDS)

It is clear that there are events which occur in response to neuromuscular activity that are essential to maintain normal muscle properties. Two factors though to influence muscle contractile properties are tension and electrical activity. To study these variables the hind limbs of 10 postpubertal female Sprague-Dawley rats were prevented from supporting the weight of the body for 4 weeks, then in situ isometric properties were determined and compared with 10 age-matched control rats. The soleus (slow plantarflexor), the medial gastrocnemius (fast plantarflexor), and the tibialis anterior (fast dorsiflexor) were studied. The suspended soleus wet weight was 42% lower and the maximum isometric twitch (Pt) and tetanic (P0) tensions were 62 and 69% lower respectively, than in the control rats. The suspended medial gastrocnemius was 18% lower in wet weight and 14 and 9% lower in P0 and Pt than the controls. No differences in wet weight, P0 or Pt were observed in tibialis anterior. Mean contraction time was 22% shorter in the soleus, 9% in the medial gastrocnemius, and unchanged in the tibialis anterior following suspension. Further, the percent of P0 attained during a 330-ms tetanus at 20 Hz was 15% lower in the suspended soleus and unchanged in the other two muscles. The fatigue index (ratio of tension after 2 min of stimulation at 40 Hz for 330 ms once per second to the maximum tension developed during the test) was unaffected by suspension in the soleus and tibialis anterior but was reduced from 49% to 36% in the medial gastrocnemius. The maximum rate of shortening of all three muscles was unaffected by suspension. These results indicate that suspension of the hind limbs selectively affects the mass and force-generating capabilities of the plantarflexors, particularly the predominantly slow soleus. In contrast, the fatigability of only the fast plantarflexor was increased whereas the slow plantarflexor was unaffected. These results, considered in light of collaborative studies, suggest that the chronic force-time levels in a muscle have an important influence on tension- and speed-related properties but not necessarily the fatigability of that muscle. Further, a marked difference in the sensitivity of the contractile elements of slow and fast muscle to this influence was evident.