Reflex changes in muscle spindle discharge during a voluntary contraction

1. This study was undertaken to determine whether low-threshold cutaneous and muscle afferents from mechanoreceptors in the foot reflexly affect fusimotor neurons innervating the plantar and dorsiflexors of the ankle during voluntary contractions. 2. Recordings were made from 29 identified muscle spindle afferents innervating triceps surae and the pretibial flexors. Trains of electrical stimuli (5 stimuli, 300 impulses per second) were delivered to the sural nerve at the ankle (intensity: 2-4 times sensory threshold) and to the posterior tibial nerve at the ankle (intensity: 1.5-3 times motor threshold for the small muscles of the foot). The stimuli were delivered while the subject maintained an isometric voluntary contraction of the receptor-bearing muscle, sufficient to accelerate the discharge of each spindle ending. This ensured that the fusimotor neurons directed to the ending were active and influencing the spindle discharge. The effects of these stimuli on muscle spindle discharge were assessed using raster displays, frequencygrams, poststimulus time histograms (PSTHs) and cumulative sums ("CUSUMs") of the PSTHs. Reflex effects onto alpha-motoneurons were determined from poststimulus changes in the averaged rectified electromyogram (EMG). Reflex effects of these stimuli onto single-motor units were assessed in separate experiments using PSTHs and CUSUMs. 3. Electrical stimulation of the sural or posterior tibial nerves at nonnoxious levels had no significant effect on the discharge of the 14 spindle endings in the pretibial flexor muscles. The electrical stimuli also produced no significant change in discharge of 11 of 15 spindle endings in triceps surae. With the remaining four endings in triceps surae, the overall change in discharge appeared to be an increase for two endings (at latencies of 60 and 68 ms) and a decrease for two endings (at latencies of 110 and 150 ms). The difference in the incidence of the responses of spindle endings in tibialis anterior and in triceps surae was significant (P less than 0.05, chi 2 test). 4. For both triceps surae and pretibial flexor muscles the electrical stimuli to sural or posterior tibial nerves had clear effects on the alpha-motoneuron pool, whether assessed using surface EMG or the discharge of single-motor units. Based on EMG recordings using intramuscular wire electrodes, the reflex effects differed for the gastrocnemii and soleus. 5. In this study, reflex changes in the discharge of human spindle endings were more difficult to demonstrate than comparable changes in the discharge of alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

An analysis of response properties of spinal cord dorsal horn neurones to nonnoxious and noxious stimuli in the spinal rat

Summary Electrophysiological properties of neurones in the spinal cord dorsal horn were studied in decerebrated, immobilized spinal rats. Extracellular recordings were performed at the thoraco-lumbar junction level. Each track was systematically located by extracellular injection of pontamine sky blue. According to their responses to mechanical peripheral stimuli, cells were classified in four classes: Class 1 cells: Cells activated only by nonnoxious stimuli. They were divided into — 1A: hair movement and/or touch and 1B: hair movement and/or touch and pressure or pressure only. Class 2 cells: Cells driven by both nonnoxious and noxious stimuli, divided into — 2A: hair movement and/or touch, pressure, pinch and/or pin-prick, and 2B: pressure, pinch and/or pin-prick. Class 3 cells: Cells only activated by noxious stimuli (pinch and/or pin-prick). Class 4 cells: Cells responding to joint movement or pressure on deep tissues.Peripheral transcutaneous or sural nerve stimulation clearly showed that class 1 cells were activated only by A fiber input while 68% of classes 2 and 3 cells received A and C input. Histological examination indicated that cells driven only by noxious input were located either in the deepest part or in the marginal zone (lamina I) of the dorsal horn. Nevertheless, some lamina I cells were also driven by both nonnoxious and noxious stimuli. In addition, there is a great deal of overlap between class 1 and class 2 cells. This fact was confirmed by considering the wide distribution in the dorsal horn of cells receiving A and C input. However, spinal organization of the different classes of cells consists of a preferential distribution rather than a strict lamination. This study indicates that properties of dorsal horn interneurones in the rat have a high degree of similarity with those previously described in other species (cat and monkey).This work was supported by the C.N.R.S. (E.R.A. 237).     

C-fiber modulation of the rat type I slowly adapting mechanoreceptor

Effects of C-fiber activation on type I slowly adapting mechanoreceptor responses were investigated in a rat in vitro nerve-skin preparation using controlled mechanical stimuli. Two changes in behavior were evoked by antidromic C-fiber stimulation: (1). The type I response to mechanical stimuli was modulated in a graded fashion by antidromic C-fiber activation. The average decrease in mechanoresponse from baseline discharge was 53% at 20-Hz, 51% at 5-Hz, and 30% at 1-Hz stimulation rate. The type I response recovered to baseline levels following termination of antidromic electrical stimulation. (2). Antidromic C-fiber activation generated a spontaneous ongoing activity in many skin units; this was independent of mechanical stimulation and outlasted electrical stimulation. The fact that neither antidromic electrical stimulation of the crushed nerve trunk nor selective A-fiber activation elicited these reactions suggests that they were mediated via action potentials of slowly conducting (C-fiber) axons. Immunohistochemical staining revealed both substance P- and calcitonin gene-related peptide-like immunoreactivity in small unmyelinated nerve fibers entering the touch dome.These results support the concepts that (1). the type I slowly adapting mechanoreceptor in rat receives input from nociceptive terminals within the touch dome. (2). The function of type I slowly adapting mechanoreceptors is modulated by axon reflex activation of nociceptor terminals, which may play a role in altering the type I response during states of mechanical allodynia and have paracrine and autocrine influences on maintenance of touch dome structure.     

Superficial and deep convergent nociceptive neurons are differentially affected by N-methyl-D-aspartate applied on the brainstem surface of the rat medullary dorsal horn.

The activation of N-methyl-D-aspartate receptors is implicated in the spinal and trigeminal processing of nociceptive information conveyed by convergent (wide dynamic range) neurons and particularly in C-fiber-evoked responses elicited by repetitive and high-intensity electrical stimulation of the neuronal receptive field. In this study, the effects of intrathecal NMDA application on the electrically evoked nociceptive responses of trigeminal subnucleus caudalis convergent neurons have been investigated. The total C-fiber-evoked activity triggered by 30 successive stimuli was divided into two components: the C-fiber input response and the 'wind-up' response. Application of 0.1 microg (in 50 microl) of NMDA evoked a bi-directional effect on the total C-fiber-evoked activity of 19 neurons tested. A significant increase in the total C-fiber-evoked activity was observed 15-25 min after the NMDA application for nine neurons located in superficial laminae II and III. In contrast, a significant decrease in the total C-fiber-evoked activity was observed 5-25 min after the NMDA application for 10 neurons located more deeply, in lamina V. The NMDA-induced modifications seen in the total C-fiber-evoked activity were likely a reflection of a significant increase or decrease in neuronal activity evoked by the C-fiber input rather than wind-up of the responses since the latter was not significantly modified by the NMDA application.These results provide evidence for a possible inhibitory role for NMDA-dependent interneurons of the superficial laminae of the medullary dorsal horn on the nociceptive activity of deep convergent neurons.     

Effects of electrical and natural stimulation of skin afferents on the gamma-spindle system of the triceps surae muscle

The aim of the present study was to investigate the extent to which skin receptors might influence the responses of primary muscle spindle afferents via reflex actions on the fusimotor system. The experiments were performed on 43 cats anaesthetized with alpha-chloralose. The alterations in fusimotor activity were assessed from changes in the responses of the muscle spindle afferents to sinusoidal stretching of their parent muscles (triceps surae and plantaris). The mean rate of firing and the modulation of the afferent response were determined. Control measurements were made in absence of any cutaneous stimulation. Tests were made (a) during physiological stimulation of skin afferents of the ipsilateral pad or of the contralateral hindlimb, or (b) during repetitive electrical stimulation of the sural nerve in the ipsilateral hindlimb, or of sural or superficial peroneal nerve in the contralateral hindlimb. Of the total number of 113 units tested with repetitive electrical stimulation of the ipsilateral sural nerve (at 20 Hz), 24.8% exhibited predominantly dynamic fusimotor reflexes, 5.3% mixed or predominantly static fusimotor reflexes. One unit studied in a preparation with intact spinal cord exhibited static reflexes at low stimulation intensities and dynamic ones at higher stimulation strengths. The remaining units (69%) were uninfluenced. When the receptor-bearing muscle was held at constant length and a train of stimuli (at 20 Hz) was applied to the ipsilateral sural nerve, the action potentials in the primary muscle spindle afferent could be stimulus-locked to the 3rd or 4th pulse in the train (and to the pulses following thereafter), with a latency of about 24 ms from the effective pulse. This 1:1 pattern of driving seemed to be mediated via static and/or dynamic fusimotor neurons. Natural stimulation influenced comparatively few units (3 of 65 units tested from the ipsilateral pad and 10 of 98 tested from the contralateral hindlimb), but when the effects were present they were quite large. The results are discussed in relation to previous studies on reflex control of fusimotor neurones from cutaneous afferents. It is suggested that the wide range of fusimotor effects from cutaneous afferent fibres observed in this study (from complete absence of any effect, via moderate excitatory and inhibitory effects, to the 'driving pattern', i.e. pulse-to-pulse response) may reflect that different gamma-motoneurones have individualized reflex profiles, and it may also indicate that groups of fusimotor neurones and spindle afferents play specific roles in different motor acts.     

Physiology and morphology of multireceptive neurons with C-afferent fiber inputs in the deep dorsal horn of the rat lumbar spinal cord

Intracellular recording techniques have been used to study neurons that respond to low- and to high-intensity mechanical stimulation of the skin of the hindpaw (wide dynamic range or multireceptive cells) in the deep dorsal horn of the fourth lumbar segment of the spinal cord, in decerebrate-spinal rats. Electrical stimulation of the A-fibers in the sciatic nerve produced a short-latency response in all 32 neurons studied. A long-latency prolonged excitation was produced in 28 of the 32 neurons when the unmyelinated afferents in the sciatic nerve were activated. This paper describes the physiological properties of 12 multireceptive cells with A- and C-fiber inputs, whose cell body location was established by horseradish peroxidase ionophoresis and the morphology of six neurons in this group whose cell bodies lay within lamina V. Single stimuli to the sciatic nerve at an intensity high enough to activate unmyelinated afferent fibers (C-fiber strength) produced two patterns of response in the neurons. In five neurons a number of long-latency postsynaptic potentials (PSPs) clearly separated from the short-latency A-fiber evoked PSPs were produced, resulting in an early discharge, a silent period, and a late discharge. The second pattern, found in seven neurons, was a long-lasting depolarization, only generated by C-strength stimuli, which continued from the early A-fiber evoked PSPs, peaked at 100-200 ms, and lasted for 300-500 ms, producing in six cases a continuous burst of action potentials with a maximal frequency at the expected latency of the C-afferent fiber input but with no clear A- and C-fiber evoked banding of the action potentials. This postsynaptic depolarization was large enough to inactivate action potentials in one cell. Repeated stimuli to the sciatic nerve (1 Hz for 10 s) at C-fiber strength produced five different types of response in the neurons. In three neurons a progressive increase in the size and duration of the C-fiber PSPs occurred, resulting in an increase in the number of action potentials (windup), whereas in two, the repeated stimulation resulted in a progressive moderate depolarization of the neurons and an increase in the total number of action potentials evoked at both early and late latencies. Large depolarizations, sufficient to partially inactivate action potentials, developed during the repeated stimulation in two cells, effectively reducing the number of spikes evoked per stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reflex activation of muscle spindles in human pretibial muscles during standing

1. Experiments were performed in standing subjects to determine whether low-threshold cutaneous and muscle afferents from mechanoreceptors in the human foot reflexly influence fusimotor neurons innervating pretibial flexor muscles. Recordings were made from 30 identified muscle-spindle afferents, four tendon-organ afferents, and one alpha-motor axon innervating the pretibial flexor muscles. The subjects stood without support or vision on a force platform while trains of electrical stimuli (5 stimuli, 300 Hz) were delivered at nonpainful intensities to the sural nerve or to the posterior tibial nerve at the ankle. 2. Seventeen of the 30 spindle endings had no background discharge, and none was activated by the sural or posterior tibial stimuli. Five silent afferents were given a background discharge by sustained pressure on the relevant tendon, but with two the discharge was dominated by a tremor rhythm obscuring any reflex response to the stimuli. Based on peristimulus time histograms (PSTHs), the sural stimuli then produced increases in discharge of two of the remaining three endings at latencies of 84 and 90 ms. These effects could not be explained by muscle stretch and are presumed to have been fusimotor mediated. 3. When the subjects stood freely without support or vision, 13 muscle-spindle endings had a background discharge, but with three endings tremor developed at the ankle and dominated the spindle discharge. Sural stimuli affected the discharge of five of nine endings unaffected by tremor. With three of these endings, there were changes in discharge that could be explained by muscle stretch.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects on flexor reflexes in patients with a complete spinal cord lesion

Summary The inhibitory effects on flexors of electrical stimulation of a distal peripheral nerve were investigated in 7 paraplegic patients having a complete spinal cord section. The stimuli (3–50 mA) were applied to the sural nerve. Their effects were investigated on: 1) the ipsi- and contralateral H reflex of the Tibialis Anterior (TA); 2) the continuous EMG activity reflexly elicited in TA by a sustained pinch of the foot and 3) on the reflexes evoked in TA by contralateral sural nerve stimulation. Sural nerve stimulation induced two peaks of facilitation of the ipsilateral TA H reflex that could be replaced by inhibition as the stimulus intensity was increased. The comparison of the effect on H reflexes and the EMG activity suggests presynaptic inhibition of Ia fibres at time intervals longer than 300 ms. The stimulation could depress the sustained EMG reflex activity and induce a period of silence whose duration increased with the intensity of the stimulation. As shown in a previous study, a sural nerve stimulation induced a reflex in TA with a prolonged (more than 130 ms) latency. This late reflex could be selectively inhibited by a contralateral sural nerve stimulation, probably at an interneuronal level. These results confirm that the late reflex in TA is similar to the one observed after Flexor Reflex Afferent (FRA) stimulation in the acute spinal cat with DOPA. In addition, they show that at least some part of the half centre organization which has been described in the acute spinal cat with DOPA is also present in the human spinal cord chronically deprived of supraspinal control.     

Reflex responses in active muscles elicited by stimulation of low-threshold afferents from the human foot.

1. Reflex responses were elicited in muscles that act at the ankle by electrical stimulation of low-threshold afferents from the foot in human subjects who were reclining supine. During steady voluntary contractions, stimulus trains (5 pulses at 300 Hz) were delivered at two intensities to the sural nerve (1.2-4.0 times sensory threshold) or to the posterior tibial nerve (1.1-3.0 times motor threshold for the intrinsic muscles of the foot). Electromyographic (EMG) recordings were made from tibialis anterior (TA), peroneus longus (PL), soleus (SOL), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles by the use of intramuscular wire electrodes. 2. As assessed by averages of rectified EMG, stimulation of the sural or posterior tibial nerves at nonpainful levels evoked a complex oscillation with onset latencies as early as 40 ms and lasting up to 200 ms in each muscle. The most common initial responses in TA were a decrease in EMG activity at an onset latency of 54 ms for sural stimuli, and an increase at an onset latency of 49 ms for posterior tibial stimuli. The response of PL to stimulation of the two nerves began with a strong facilitation of 44 ms (sural) and 49 ms (posterior tibial). With SOL, stimulation of both nerves produced early inhibition beginning at 45 and 50 ms, respectively. With both LG and MG, sural stimuli produced an early facilitation at 52-53 ms. However, posterior tibial stimuli produced different initial responses in these two muscles: facilitation in LG at 50 ms and inhibition in MG at 51 ms. 3. Perstimulus time histograms of the discharge of 61 single motor units revealed generally similar reflex responses as in multiunit EMG. However, different reflex components were not equally apparent in the responses of different single motor units: an individual motor unit could respond slightly differently with a change in stimulus intensity or background contraction level. The multiunit EMG record represents a global average that does not necessarily depict the precise pattern of all motor units contributing to the average. 4. When subjects stood erect without support and with eyes closed, reflex patterns were seen only in active muscles, and the patterns were similar to those in the reclining posture. 5. It is concluded that afferents from mechanoreceptors in the sole of the foot have multisynaptic reflex connections with the motoneuron pools innervating the muscles that act at the ankle. When the muscles are active in standing or walking, cutaneous feedback may play a role in modulating motoneuron output and thereby contribute to stabilization of stance and gait.     

Reflexes induced by nerve stimulation in walking cats with implanted cuff electrodes

Summary Neural cuffs, implanted around various hindlimb nerves (sural, common peroneal, posterior tibial), were used to deliver brief stimulus trains to unrestrained cats walking on a treadmill. The resulting perturbations of the step cycle were evaluated by analyzing the EMG bursts recorded from the ankle extensors and by high speed cinematography. It was found that relatively weak stimulation (1.4 to 2 X T) of the posterior tibial nerve was very effective in eliciting a prolongation of the flexion phase provided the stimuli were applied just prior to the expected onset of the ankle extensor EMG burst. This ipsilateral hyperflexion was correlated with a prolongation of the contralateral extension. The same stimuli applied during stance usually evoked a yielding of the stimulated leg and a prolongation of the ongoing contralateral stance. In addition to these flexor and extensor reflex effects, it was found that low threshold stimulation of the sural and common peroneal nerves resulted in a powerful reflex activation of the ankle extensors. In contrast, stimulation of the gastrocnemius-soleus nerve (a muscle nerve) produced no discernible behavioral effects, even for stimuli at 3 X T, indicating that the observed reflexes are probably mediated by cutaneous afferents. The results were largely confirmed in experiments using the same cuffs implanted in spontaneously walking premammillary cats.     

Effects of heterotopic‐ and segmental counter‐stimulation on the nociceptive withdrawal reflex in humans

A nociceptive withdrawal reflex in 12 human volunteers was elicited by painful electrical stimulation applied to the cutaneous innervation area of the sural nerve. The evoked electromyographic reflex activities were recorded with surface electrodes placed on the short head of the biceps femoris muscle ipsi‐lateral to sural nerve stimulation, before, during and after conditioning stimuli. The nociceptive withdrawal reflex was conditioned by nociceptive and non‐nociceptive, heterotopic and segmental counter‐stimulation. Heterotopic nociceptive counter‐stimulation and segmental nociceptive counter‐stimulation were induced by ice water applied to the contra‐lateral hand and foot, respectively. Heterotopic nociceptive counter‐stimulation produced a significant inhibition of the nociceptive withdrawal reflex and the associated pains rating to sural nerve stimulation. Segmental nociceptive counter‐stimulation inhibited the pain rating and tended to inhibit the nociceptive withdrawal reflex. There was no obvious correlation between visual analogue scale (VAS) and the nociceptive withdrawal reflex elicited by sural nerve stimulation neither in the group nor in the individual subject. This suggests that the nociceptive withdrawal reflex cannot always be used as a quantitative measure of pain.     

Monosynaptic and oligosynaptic contributions to human ankle jerk and H-reflex

Studies were undertaken in normal subjects to determine whether it is possible for oligosynaptic reflex pathways to affect motoneuron discharge in the ankle jerk and H-reflex of the soleus. It is argued that if the rising phase of the increase in excitability of the soleus motoneuron pool produced by tendon percussion or by electrical stimulation of the peripheral nerve lasts more than a few milliseconds and if the increase in excitability takes several milliseconds to reach the threshold for motoneuron discharge, these reflexes are unlikely to be exclusively monosynaptic. In relaxed subjects, changes in excitability of the soleus motoneuron pool produced by tendon percussion and by electrical stimulation of the tibial nerve were examined using conditioning stimuli just below threshold and a test H-reflex just above threshold for a reflex response. The increase in excitability due to tendon percussion had an average rise time of 10.8 ms and a total duration of approximately 25 ms. With electrical stimulation the rising phase appeared shorter, but it could not be measured accurately due to afferent refractoriness. In single motor units, the rise times of the composite excitatory postsynaptic potentials (EPSPs) set up by subthreshold tendon percussion and by subthreshold electrical stimulation of the tibial nerve were estimated from changes in the probability of discharge of voluntarily activated single motor units. Rise times were significantly longer with tendon percussion (mean +/- SD, 7.1 +/- 2.3 ms; n = 34) than with electrical stimulation (2.4 +/- 1.4 ms; n = 32). In four experiments in which a number of motor units were studied using identical mechanical and identical electrical stimuli, the poststimulus time histograms (PSTHs) for each stimulus were pooled to provide an estimate of the rise time of the excitability change in the motoneuron pool. The mean rise times of these four samples were 10.5 ms with mechanical stimulation and 4.5 ms with electrical stimulation. The spontaneous variability in latency of reflexly activated single motor units was 0.8-3.1 ms (average SD, 0.34 ms) in the tendon jerk, and 0.6-1.4 ms (average SD, 0.19 ms) in the H-reflex. Comparison of these figures with the measurements of rise time given above suggests that the composite EPSPs are larger than the background synaptic noise. With six motor units, the timing of reflex discharge in the tendon jerk when the subject was relaxed was compared with the timing of the change in probability of discharge due to apparently identical percussion when the units were activated voluntarily.(ABSTRACT TRUNCATED AT 400 WORDS)     

Morphine-sensitive late components of the flexion reflex in the neonatal rat

The 8-15-day-old rat spinal cord was isolated together with peripheral nerves innervating a hindlimb. Multiunit neural discharges in response to electrical stimulation of a cutaneous nerve (sural, plantar of superficial peroneal nerve) were recorded from a flexor nerve (deep peroneal nerve or nerve innervating the hamstring muscles). Attempts were made to find relations between the magnitude of the flexion reflex discharges and the sizes of the volleys in the myelinated or unmyelinated afferent fibers. The neonatal flexion reflex discharges due to myelinated fiber volleys were exaggerated when compared with those in the adult rats. Higher stimulus strengths recruited later components of the flexion reflex discharges. The observed increment of the flexion reflex discharges was precisely associated with the recruitment of unmyelinated afferent fibers in the nerve. These late flexion reflex discharges were shown to be depressed by the opiate analgesic morphine in a naloxone-reversible manner.     

Reflex responses evoked in the adrenal sympathetic nerve to electrical stimulation of somatic afferent nerves in the rat

The present study was initiated to determine the role of somatic A (myelinated) and C (unmyelinated) afferent fibers in both responses of increases and decreases in adrenal sympathetic nerve activities during repetitive mechanical pinching and brushing stimulations of the skin in anesthetized rats with central nervous system (CNS) intact. Accordingly, changes in adrenal sympathetic nerve activity resulting from repetitive and single shock electrical stimulation of various spinal afferent nerves, especially the 13th thoracic (Th13) spinal nerve and the sural nerve, were examined in urethane/chloralose-anesthetized rats. Repetitive electrical stimulation of A afferent fibers in Th13 spinal or sural nerve decreased the adrenal nerve activity similarly as brushing stimulation of skin of the lower chest or hindlimb did, while repetitive stimulation of A plus C afferent fibers of those nerves increased the adrenal nerve activity as pinching stimulation of those skins did. Single shock stimulation of spinal afferent nerves evoked various reflex components in the adrenal nerve: an initial depression of spontaneous activity (the early depression); the following reflex discharge due to activation of A afferent fibers (the A-reflex); a subsequent reflex discharge due to activation of C afferent fibers (the C-reflex); and following post-excitatory depressions. These reflexes seem to be mediated mainly via supraspinal pathways since they were abolished by spinal transection at the C1-2 level. Although the supraspinal A- and C-reflexes could be elicited from stimulation of a wide variety of spinal segmental afferent levels, the early depression was more prominent when afferents at spinal segments closer to the level of adrenal nerve outflow were excited. It is suggested that the decreased responses of the adrenal nerve during repetitive electrical stimulation of A afferent nerve fibers are attributable to summation of both the early depression and post-excitatory depression evoked by single shock stimulation, while the increased responses during repetitive stimulation of A plus C afferent fibers are attributable to summation of the C-reflex after single shock stimulation. In spinalized rats, repetitive stimulation of Th13 always increased the adrenal nerve activities regardless of whether A fibers alone or A plus C fibers were stimulated, just as brushing and pinching of the lower chest skin always increased them. The increased responses in spinal animals seem to be related to the fact that single electrical stimuli of Th13 produced A- and C-reflexes of spinal origin without clear depressions.     

Reflex influences on muscle spindle activity in relaxed human leg muscles

The study was designed to determine whether low-threshold cutaneous and muscle afferents from the foot reflexly activate gamma-motoneurons innervating relaxed muscles of the leg. In 15 experiments multiunit recordings were made from 21 nerve fascicles innervating triceps surae or tibialis anterior. In a further nine experiments the activity of 19 identified single muscle spindle afferents was recorded, 13 from triceps surae, 5 from tibialis anterior, and 1 from extensor digitorum longus. Trains of electrical stimuli (5 stimuli, 300 Hz) were delivered to the sural nerve at the ankle (intensity, twice sensory threshold) and the posterior tibial nerve at the ankle (intensity, 1.1 times motor threshold for the small muscles of the foot). In addition, a tap on the appropriate tendon at varying times after the stimuli was used to assess the dynamic responsiveness of the afferents under study. The conditioning electrical stimuli did not change the discharge of single spindle afferents. Recordings of rectified and averaged multiunit activity also revealed no change in the overall level of background neural activity following the electrical stimuli. The afferent responses to tendon taps did not differ significantly whether or not they were preceded by stimulation of the sural or posterior tibial nerves. These results suggest that low-threshold afferents from the foot do not produce significant activation of fusimotor neurons in relaxed leg muscles, at least as judged by their ability to alter the discharge of muscle spindle afferents. As there may be no effective background activity in fusimotor neurons innervating relaxed human muscles, it is possible that these inputs from the foot could influence the fusimotor system during voluntary contractions when the fusimotor neurons have been brought to firing threshold. In one subject trains of stimuli were delivered to the posterior tibial nerve at painful levels (30 times motor threshold). They produced an acceleration of the discharge of a spindle in soleus at a latency of approximately 125 ms, in advance of detectable activity in skeletomotor neurons and before an increase in muscle length was noted. It presumably resulted from activation of gamma-motoneurons innervating soleus by small myelinated afferents (A-delta range).     

The effect of transcranial magnetic stimulation on reciprocal inhibition in the human leg.

The effect of magnetic stimulation on reciprocal Ia inhibition of the human leg was investigated. Stimulation of the common peroneal nerve at the fibula head at the threshold of the alpha motoneuron axons resulted in inhibition of the soleus (SOL) H reflex at a conditioning-test interval of 2 ms. Magnetic stimulation over the contralateral motor cortex resulted in complex modulations of the SOL H reflex, including a short latency facilitation followed by inhibition. This inhibition may have been conveyed by Ia inhibitory interneurons projecting to SOL motoneurons. To test for convergence, whether or not the magnetic stimulation was capable of facilitating disynaptic reciprocal Ia inhibition of the SOL H reflex induced by stimulation of the peroneal nerve, the two stimuli were given together or separately. We observed the inhibition significantly increased when the two stimuli were given together than separately. These results suggest that the Ia inhibitory interneurons projecting to SOL motoneurons in humans might receive convergent input from the motor area of the brain and from Ia afferents of the tibialis anterior (TA) muscle in humans as well as in other animals.     

Differential projection of the sural nerve to early and late recruited human tibialis anterior motor units: change of recruitment gain

The effect of a stimulation of the cutaneous sural nerve [three shocks, 2.5 × perception threshold (PT)] was studied on the tibialis anterior (TA) H-reflex and single voluntarily activated TA motor units using post-stimulus time histograms (PSTH). In both cases, when studying only the first recruited motor units, an inhibition with a delay of 10 ms, in relation to the monosynaptic latency of Ia afferents in the common peroneal nerve, was observed. This inhibition had a duration of 10–20 ms. The inhibition was evoked by low-threshold cutaneous fibres, since it could be seen at a stimulation strength close to the perception threshold. The central delay of the inhibition was calculated in two subjects to be 1.8 ms and 1.2 ms respectively. The TA motor units were characterized by their recruitment threshold and minimal firing frequency and the effect of the sural nerve stimulation was subsequently investigated. Early recruited low frequency motor units were found to be inhibited, whereas later recruited motor units with a higher minimal firing frequency were facilitated. Similarly small TA H-reflexes were inhibited, whereas large reflexes were facilitated. This difference in the effect of the sural nerve stimulation was not caused by a difference in the descending command, since the same early recruited motor unit was still inhibited when firing at a high frequency and at a high torque level. Stimulation of the femoral nerve was found to produce a monosynaptic facilitation of the TA H-reflex and a heteronymous monosynaptic peak in the PSTH of single motor units. A stimulation of the sural nerve increased the size of the reflex facilitation, but had no effect on the size of the monosynaptic peak in the PSTH of the single motor units. It is concluded that the effect of the sural nerve stimulation on human TA motor units is similar to observations in the cat and that a similar interneuronal system may be responsible. It is furthermore suggested that the sural nerve stimulation increases the recruitment gain of the TA motoneuronal pool.     

Stability of long term facilitation and expression of zif268 and Arc in the spinal cord dorsal horn is modulated by conditioning stimulation within the physiological frequency range of primary afferent fibers

Long term facilitation (LTF) of C-fiber-evoked firing of wide dynamic range neurons in the spinal dorsal horn in response to conditioning stimulation (CS) of afferent fibers is a widely studied cellular model of spinal nociceptive sensitization. Although 100 Hz CS of primary afferent fibers is commonly used to induce spinal cord LTF, this frequency exceeds the physiological firing range. Here, we examined the effects of electrical stimulation of the sciatic nerve within the physiological frequency range on the magnitude and stability of the C-fiber-evoked responses of wide dynamic range neurons and the expression of immediate early genes (c-fos, zif268, and Arc) in anesthetized rats. Stimulation frequencies of 3, 30 and 100 Hz all induced facilitation of similar magnitude as recorded at 1 h post-CS. Strikingly, however, 3 Hz-induced potentiation of the C-fiber responses was decremental, whereas both 30 and 100 Hz stimulation resulted in stable, non-decremental facilitation over 3 h of recording. The number of dorsal horn neurons expressing c-fos, but not zif268 or Arc, was significantly elevated after 3 Hz CS and increased proportionally with stimulation rate. In contrast, a stable LTF of C-fiber responses was obtained at 30 and 100 Hz CS, and at these frequencies there was a sharp increase in zif268 expression and appearance of Arc-positive neurons. The results show that response facilitation can be induced by stimulation frequencies in the physiological range (3 and 30 Hz). Three hertz stimulation induced the early phase of LTF, but the responses were decremental. Arc and zif268, two genes previously coupled to LTP of synaptic transmission in the adult brain, are upregulated at the same frequencies that give stable LTF (30 and 100 Hz). This frequency-dependence is important for understanding how the afferent firing pattern affects neuronal plasticity and nociception in the spinal dorsal horn.     

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by descending control. This pEPSP is released from inhibition immediately after injury but does not produce a long-lasting reflex because of a lack of motoneuron excitability. With chronic injury the motoneuron excitability is increased markedly, and the pEPSP then triggers sustained motoneuron discharges associated with long-lasting reflexes and muscle spasms.     

Differential synaptic effects on physiological flexor hindlimb motoneurons from cutaneous nerve inputs in spinal cat.

1. We previously demonstrated in the spinal cat that superficial peroneal cutaneous nerve stimulation produced strong reflex contraction in tibialis anterior (TA) and semitendinosus (St) muscles but unexpectedly produced mixed effects in another physiological flexor muscle, extensor digitorum longus (EDL). The goal of the present study was to further characterize the organization of ipsilateral cutaneous reflexes by examining the postsynaptic potentials (PSPs) produced in St, TA, and EDL motoneurons by superficial peroneal and saphenous nerve stimulation in decerebrate, spinal cats. 2. In TA and St motoneurons, low-intensity cutaneous nerve stimulation that activated only large (A alpha) fibers [i.e., approximately 2-3 times threshold (T)], typically produced biphasic PSPs consisting of an initial excitatory phase and subsequent inhibitory phase (EPSP, IPSP). Increasing the stimulus intensity to activate both large (A alpha) and small (A delta) myelinated cutaneous fibers supramaximally (15-45 T) tended to enhance later excitatory components in TA and St motoneurons. 3. In EDL motoneurons, 2-3 T stimulation of the superficial peroneal nerve evoked initial inhibition (of variable magnitude) in 7/10 EDL motoneurons tested, with either excitation (n = 2) or mixed effects (n = 1) observed in the remaining EDL motoneurons. Saphenous nerve stimuli produced excitation either alone, or preceded by an inhibitory phase in EDL. Increasing the stimulus intensity enhanced later inhibitory influences from superficial peroneal and excitatory influences both from superficial peroneal and saphenous nerve inputs in EDL motoneurons. 4. Short-latency (less than 1.8 ms) EPSPs were observed in a few motoneurons in all reflex pathways examined, except for EPSPs in EDL motoneurons evoked by saphenous stimulation. IPSPs with central latencies less than 1.8 ms were also produced by both saphenous (TA, n = 1; EDL, n = 2) and superficial peroneal (EDL, n = 4) nerve stimulation. 5. The results, in comparison with other reports employing spinal and nonspinal preparations, suggest that removal of influences from higher centers reveals inhibitory circuits from the superficial peroneal and saphenous nerves to EDL motoneurons in the spinal preparation. The inhibitory inputs observed are thought to reflect the activation of "specialized" reflex pathways. Additionally, the demonstration of short-latency EPSPs and IPSPs suggest that the minimal linkage in both the excitatory and inhibitory cutaneous reflex pathways examined is disynaptic. The results are discussed in relation to previous studies on classically conditioned flexion reflex facilitation in spinal cat.