The silent period in the stretch response of ia-activated dorsal spino-cerebellar tract neurons to sinusoidal muscle stretch in cats

By means of extracellular recordings of action potentials the stretch responses of single neurons of Clarke's column were analysed. The neurons were monosynaptically activated from Ia afferents of both ipsilateral gastrocnemius muscles. When stretch cycles of more than 0.2 mm amplitude and frequencies above 2 Hz were applied to the gastrocnemius muscles, the discharging was found to cease during the period of stretch release, whereas the average discharge rate was found to increase. In the frequency range between 0.1 and 10 Hz a sinewave of stretch frequency — the response sinewave — fitted to the non-zero bins of cycle histograms described the stretch response at small and large amplitudes equally well. The amount of increase in the average firing rate corresponded quite well to the portion of the response sinewave below the zero discharge rate. This indicates that the occurance of discharge pauses and the relation of the average discharge rate to frequency and amplitude of stretch can be described successfully by a half-wave rectification of the response at zero discharge rate. If one regards the shape of cycle histograms to be a nearly sinusoidal modulation plus a non-linear clipping at zero the application of linear systems analysis is worthwhile in describing the response not only at very small amplitudes but in the whole range of muscle stretch.     

Information transmission by isolated frog muscle spindle

Transmission of sensory information was calculated for the isolated frog muscle spindle receptor, using Shannon's information measure. Sinusoidal movements, random noise stretches, and sinusoids with superimposed auxiliary noise were applied as stimuli. In addition, the static prestretch level of the intrafusal muscle bundle was adjusted between resting length (L0) and L0 + 600 micron, so that the analysis of the information transmission properties covered the entire dynamic range of the sensory receptor organ. Sinusoidal stretches below 2 Hz evoked smoothly modulated cycle histograms, which were approximately linearly related to the stimulating sinewave. The transinformation rates under these conditions were generally low (5-17 bit X s-1), regardless of the amplitude of the applied movement. Increasing prestretch enhanced the modulation depth of the cycle histograms considerably, but increased the transinformation rates by less than 10 bit X s-1. By contrast, sinusoids above 2 Hz evoked clearly nonlinear cycle histograms, because each action potential was firmly phase-locked to a small segment of the stretch cycle. Under these conditions the transinformation rates grew larger with increasing stimulus frequency and approached 130 bit X s-1 at 60 Hz. Small amplitude sinusoidal stretches, however, evoked considerable transinformation rates in the high frequency region only then, when the spindle receptor was extended to higher prestretch levels. Random stretches evoked transinformation rates between 5 and 30 bit X s-1 depending on both the prestretch level and the intensity of the noise stimulus. The linear response components carried only about 25% of the transinformation rates transmitted by both the linear and nonlinear response components. Auxiliary noise stimuli greatly improved the information transmission of sinusoidal stretches. For example, a pure sinusoid evoked 5 bit X s-1. Adding a noise signal with equal energy to the sinusoidal movement elicited 20 bit X s-1. This facilitation effect of auxiliary noise was restricted to low frequency sinusoidal stimuli. The present results are discussed with respect to the information transmission properties of various sensory systems evaluated by either the same or different information processing procedure as that used in the present study. The functional significance of high transinformation rates sent by the muscle spindle to the central nervous system is discussed with respect to motor control.     

Effect of the amplitude and frequency of sinusoidal stimulation on the harmonic distortion of the response of sensory terminations of muscle spindles

Harmonic distortion (HD) from 1,055 responses of muscle spindles sensory endings to sinusoidal stretches (frequency range 0.0008 to 0.8333 Hz, amplitude range 0.019 to 3.09 mm) has been studied in the cat soleus muscle. Sixty-six per cent were primary afferents (Ia) and 34% secondary (II). HD mean value (0.28) did not show any significant differences between both types of endings. Analysis of variance for HD versus stimulation amplitude showed a greater HD when stretch amplitudes were beyond 1.599 mm or less than 0.031 mm on primary afferents (p less than 0.001) and less than 0.070 mm on secondary (p less than 0.001). The effect of stimulus frequency was also significant (p less than 0.01 Ia and p less than 0.001 II), however only at 0.8333 Hz and in secondary endings HD was significantly higher. The silent period in the response, at release of stretch, caused by half wave rectification could explain about 50% of measured HD.     

Reverse correlation analysis of the stretch response of primary muscle spindle afferent fibers

The nonlinear responses of deefferented primary muscle spindle afferent fibers to muscle stretching consisted of a train of action potentials which was analyzed when random changes in muscle length (band-limited gaussian white noise) were applied in cats. The upper cutoff frequency of the applied noise (the source stimulus) was varied between 1.6 and 570 Hz; the amplitude of the random input was varied between 0.002 and 1.2 mm. In a previous report the reverse correlation of 1st and 2nd order was studied for its ability to analyze data of a continuous input signal and pulsatile events in the output. Computations of the Wiener kernelsh ₁ andh ₂ or their equivalents, the perispike averages of the 1st and 2nd order, were computed from the random stretch responses of muscle-spindle afferents. Then the 1st- and the 2ndorder predictions and the summation of both to random muscle stretch was estimated. A general finding was that the 1st-order component was approximately 10 times that of the 2nd-order component, when both were combined in approximation procedures to give the closest prediction of observed responses to random test stimuli. The approximation was poor when the source stimulus was less than 0.03 mm and improved when it was greater. With the increase in the upper cutoff frequency of the random source input, the approximation worsened continuously. Predictions to ramp-and-hold stimuli were computed, as well as responses to random stimulation. Limiting the upper cutoff frequency did not diminish the value of the techniques applied.     

Spike discharges of skeletomotor neurons during random noise modulated transmembrane current stimulation and muscle stretch

 Spike discharges of skeletomotor neurons innervating triceps surae muscles elicited by white noise modulated transmembrane current stimulation and muscle stretch were studied in decerebrated cats. The white noise modulated current intensity ranged from 4.3 to 63.2 nA peak-to-peak, while muscle stretches ranged from 100 μm to 4.26 mm peak-to-peak. The neuronal responses were studied by averaging the muscle length records centered at the skeletomotor action potentials (peri-spike average, PSA) and by Wiener analysis. Skeletomotor spikes appeared after a sharp peak in PSA of the injected current, preceded by a longer-lasting smaller wavelet of either depolarizing or hyperpolarizing direction. The PSA amplitude was not related to the injected current amplitude nor showed any differences related to the motor unit type. The PSA amplitudes were virtually independent of the stretching amplitude σ, after an initial increase with stretching amplitudes in the range of 15–40 μm (S.D.), or 100–270 μm peak-to-peak.Analyses of cross-spectra indicated a small or absent increase in gain with frequency in response to injected current, but about 20 dB/decade in the range 10–100 Hz in response to muscle stretch. The peaks of both Wiener kernels in response to current injection appear to decrease with the amplitude of injected current, but this decrease was not statistically significant. The narrow first-order kernels suggest that the transfer function between the current input and spike discharge is lowpass with a wide passband, i.e. there is very little change in dynamics. The values of the second-order kernels appear to be nonzero only along the main diagonal. This is characteristic of a simple Hammerstein type cascade, i.e. a zero memory nonlinearity followed by a linear system. Small values of second-order kernels away from the origin and narrow first-order kernels suggest that the linear cascade contributes very little to the overall dynamic response.In contrast to Wiener kernels found in response to current injection, the Wiener kernels in response to stretch showed a decreasing trend with stretch amplitude. The size of the second-order kernels decreased to a somewhat larger extent with input amplitude than that of the first-order kernels, indicating an amplitude-dependent nonlinearity. Overall, the transformation between length and spike output was described as an LNNL cascade with second-order nonlinearities. Received: 1 April 1993/Accepted in revised form: 24 March 1994     

Observations on phase-locking within the response of primary muscle spindle afferents to pseudo-random stretch

In order to uncover encoder properties of primary muscle spindle afferent fibers, time coupling (phase-locking) of action potentials on cyclic muscle stretch was studied by means of pseudo-random noise. In cats Ia action potentials were recorded from dorsal root filaments and the gastrocnemius muscles of one hind leg were stretched. The stimulus time course was a determined sequence of randomly varying muscle length which could be applied repeatedly (sequence duration 0.6 or 20 s). The noise amplitude (standard deviation of displacements) was varied between 5 and 300 m, the upper cut-off frequency of noise f _c was varied between 20 and 100 Hz. The responses to the consecutive pseudo-random noise cycles were displayed as raster diagrams and cycle histograms. Phaselocking characterized the responses at all noise amplitudes outside the near threshold range (>10 m). The higher and f _c , the stronger was the phase-locking of impulses on the stretch. When and f _c were selected to achieve high mean stretch velocities of about 500 mm/s, phase-locking was as precise as 0.15 ms, measured as the variability of spike occurrences with respect to stretch. The rasters obtained with low noise amplitudes (<40 m) showed a loose phase-locking and this gave insight into underlying mechanisms: The elicitation of action potentials caused by dynamic stretch can be prevented by a post-spike depression of excitability. This disfacilitation was very effective in counteracting weak stretch components within the random sequence and less effective or even missing when relatively strong stretch components could force the spike elicitation. This led to the reestablishment of phase-locked patterns. The results were discussed in relation to the known encoder models.     

Characterization of muscle spindle afferents in the adult mouse using an in vitro muscle-nerve preparation

We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli. Responses were measured at both room (24°C) and muscle body temperature (34°C). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length [Lo]). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10-100 Hz) and amplitude ranges tested (5-100 μm). Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. Cooling the muscle to 24°C decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. The ramp component of stretch generated dynamic firing responses. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.     

Effect of cycle frequency and excursion amplitude on work done by rat diaphragm muscle

Strips of isolated rat diaphragm muscle were attached to a servomotor-transducer apparatus, and the muscle length was cycled in a sinusoidal fashion about the length at which maximum isometric twitch force was developed, Lo. The amplitude of the length displacement (excursion amplitude) and rate of cycling were varied between 3 and 13% Lo and 1-4 Hz respectively. The muscle was tetanically stimulated (100 Hz, supramaximal voltage, stimulus duration (duty cycle) 20% of the length cycle period) during the shortening stage of the imposed length cycle at the phase that yielded maximum net positive work. The force and displacement of the muscle were recorded. Work per cycle was calculated from the area of the loop formed by plotting force against length for one full stretch-shorten cycle. Work per cycle decreased, but power increased, as cycle frequency was increased from 1 to 4 Hz. Maximum work done per cycle was about 12.8 J/kg at a cycle frequency of 1 Hz. Maximum mean power developed was about 27 W/kg and occurred at a cycle frequency of 4 Hz. Work and power were maximum at an excursion amplitude of 13% of Lo (i.e., Lo +/- 6.5%). Measured work and power output are considerably less than values estimated from length-tension and force-velocity curves.     

Optimal vibration stimulation to the neck extensor muscles using hydraulic vibrators to shorten saccadic reaction time

Optimal vibration stimulation to the neck extensor muscles using hydraulic vibrators to shorten the saccadic reaction time was examined. Subjects were 14 healthy young adults. Visual targets (LEDs) were located 10 degrees left and right of a central point. The targets were alternately lit for random durations of 2-4 seconds in a resting neck condition and various vibration conditions, and saccadic reaction times were measured. Vibration amplitude was 0.5 mm in every condition. The upper trapezius muscles were vibrated at 40, 60, 80, and 100 Hz in a sub-maximum stretch condition in which the muscles were stretched at 70% of maximum stretch. In addition, the muscles were vibrated at 60 Hz with the muscles maximally stretched, with 70% vertical pressure without stretching, and with vibration applied to the skin in the same area as the muscle vibration. At 60, 80, and 100 Hz at 70% maximum stretch, saccadic reaction time shortened significantly compared with the resting neck condition. However, no significant difference in the reaction time was observed among the frequencies. The saccadic reaction times in the maximum stretch condition, muscle pressure condition, and skin contact condition did not differ significantly from that in the resting neck condition. Vibration stimulation to the trapezius with 60-100 Hz frequencies at 0.5 mm amplitude in the sub-maximum stretch condition was effective for shortening saccadic reaction time. The main mechanism appears to be Ia information originating from the muscle spindle.     

The cerebellum and initiation of movement: the stretch reflex

Studies of the stretch reflex in decerebrate cats indicate a phase advance of peak sinusoidal tension in steady-state cycles between 0.1 and 10 Hz. This phase advance is reduced in acute and chronic cerebellectomy, as shown in previous investigations. Also, the augmentation of muscle peak tension in initial sinusoidal stretch cycles at 0.5-5 Hz has been found to be reduced during the time of reflex and motor instability in the several months following cerebellar ablation. This report shows the increased amplitude and phase lead of integrated electromyographic activity in initiating sinusoidal stretch cycles in the decerebrate cat. These reflex aspects are demonstrated in relation to the discharge of neurons in the dorsal spinocerebellar tract and of cerebellar cortical Purkinje cells in initial sinusoidal cycles. The intensity and phase advance of the discharge in dorsal spinocerebellar tract neurons is altered little, but these features are usually increased in Purkinje cells during initial stretches compared to continuous cycling. In terms of overall motor control, these findings are compatible with concepts of movement control, modulated by the cerebellum, in which the discharge of antagonist motor neurons is regulated in concert with that of agonist muscles upon initiation and termination of movement.     

Dynamic behavior of excised dog rib cage: dependence on muscle

To assess the contribution of the rib cage to chest wall elastance and hysteresis, we measured force-displacement behavior of the isolated canine rib cage during sinusoidal forcing of the sternum in the midsagittal plane at low frequencies (0.02-2.0 Hz). Elastance of the rib cage was nearly invariant with frequency of forcing from 0.02 to 1.0 Hz and decreased with increasing amplitude. Hysteresis, the width of the force-displacement loop at middisplacement (zero displacement), was nearly constant with frequency below 1.0 Hz and increased with increasing amplitude of forcing. Removal of muscle reduced elastance and hysteresis of the rib cage substantially. The data suggest that the excised dog rib cage shows dynamic behavior similar to that of the intact human rib cage and chest wall and that respiratory muscle is responsible for a major part of the behavior of the passive chest wall. We also calculated the major and minor stiffnesses in the sagittal plane, which differed by a factor of 3-11, and their directions lay close to the dorsoventral and cephalocaudal axes, respectively. Removal of muscle reduced the stiffnesses but did not change their directions. Thus, although respiratory muscles impede motion in the sagittal plane, they do not alter its pattern.     

Characteristics of the sensory discharge of the muscle spindle in Xenopus laevis

Single isolated muscle spindles from the toad Xenopus laevis were studied with regard to their response to different levels of steady stretch and to their response to small precisely controlled length variations. The spectral distribution of the applied variations was designed to be essentially uniform in the region between 0.04 Hz and a number of selectable upper limits none exceeding 20 Hz. The results obtained relate to the statistics of receptor discharge intervals, to receptor transfer functions and to the coding and decoding of sensory information. The conclusion is that spectral analysis techniques can be used to clarify many aspects of muscle spindle behavior.     

The chemo-mechanical coupling relation in the oscillatory contraction-relaxation cycles of insect fibrillar muscle.

The mechanical properties and the activity of the myofibrillar ATPase have been investigated at 21 degrees C on glycerinated back muscle from the water-bug Lethocerus colossicus. When the fibres were held under isometric conditions after stretching them by 0.5--4%, the ATPase required to maintain a given tension increases from 19 to 39 p-moles ATP split for each mg of tension developed as the Ca2+ level is increased from 10(-7) to up to 10(-5) M. The mechanical properties and the ATPase activity have been determined for Ca2+-activated fibres using sinusoidal frequencies of 1--30 HZ and oscillatory amplitudes of 0.5--6% peak-to-peak. In this way the R.M.S. velocity of sinusoidal movement was varied between 0.1-10 mm/sec. The rate of ATP splitting associated with oscillatory tension development, the dynamic tension cost, increases both with Ca2+ and with frequency of oscillation (at 1% peak-to-peak amplitude), becoming as high as four times the isometric value. The oscillatory power output which can be obtained is increased when the Ca2+ level is raised from 10(-7) to 10(-5) M or towards higher amplitudes of oscillation. The chemo-mechanical coupling efficiency increases proportionally with the R.M.S. velocity of muscle movement. In presence of 10(-5) M Ca2+ optimal efficiencies of 5.5--6.2 kcal work per mole ATP split are obtained at R.M.S. velocities of 1.3--2 muscle lengths/sec. The ability of the muscle fibres to perform osciillatory work at the higher frequencies was much reduced at lower Ca2+ levels of 10(-6) or 10(-7) M and the maximal efficiencies never exceeded 2.2 kcal/mole.     

The relative sensitivity of Renshaw cells to orthodromic group Ia volleys caused by static stretch and vibrations of extensor muscles.

1. Activity of Renshaw cells monosynaptically excited by ventral root stimulation and disynaptically excited by electric stimulation of the group Ia afferents in the gastrocnemius-soleus (GS) nerve, was recorded in precollicular decerebrate cats. The response of these units to prolonged vibration applied longitudinally to the deefferented GS muscle was then compared with that elicited by static stretch of the homonymous muscle, for comparable frequencies of discharge of the group Ia afferents. 2. Small-amplitude vibration of the GS muscle at 200/sec for one second produced a sudden increase in the discharge rate of Renshaw cells, which gradually decreased within the first 100 msec of vibration to reach steady albeit lower level than that obtained during the first part of vibration. The response of the Renshaw cells during the first 100 msec of vibration (phasic response) and that elicited during the last 500 msec of vibration (tonic response) were evaluated for different frequencies of sinusoidal stretch. The mean increase in the firing frequency per imp./sec in the Ia afferents was also calculated using the total one-second period. 3. The response of Renshaw cells to muscle vibration increased with the frequency of vibration and, over the value of 10/sec, appeared to be linearly related to the frequency of the input, at least up to the frequency of 150/sec. Since vibration was of sufficient amplitude to produce driving of all the primary endings of muscle spindles, the responses were expressed as mean increases in the discharge rate of Renshaw cells per average impulse/sec in the Ia afferents. The discharge of the Renshaw cell increased on the average by 2.90 and 1.08 imp./sec per each imp./sec in the Ia afferents during the phasic and the tonic component of the response respectively, while the response calculated during the whole period of vibration corresponded on the average to 1.45 imp./sec per each imp./sec in the Ia afferents. 4. The Renshaw cells tested above responded also with increasing frequencies of discharge to increasing levels of static extension of the GS muscle. In particular the discharge frequency of Renshaw cells was on the average linearly related to muscle extension, at least for values ranging from 0 to 8 mm. The mean increase in discharge rate as a function of the static extension corresponded on the average to 0.89 imp./sec/mm. Since the discharge rate of the primary endings of muscle spindles recorded from the deefferented GS muscle increased by 2.62 imp./sec/mm, it appears that the mean increase in the discharge rate of Renshaw cells as a function of static extension corresponded to 0.34 imp./sec per each imp./sec in the Ia afferents.     

History-dependence of isometric muscle force: effect of prior stretch or shortening amplitude

It is well-recognised that steady-state isometric muscle force is decreased following active shortening (force depression, FD) and increased following active stretch (force enhancement, FE). It has also been demonstrated that passive muscle force is increased following active stretch (passive FE). Several studies have reported that FD increases with shortening amplitude and that FE and passive FE increase with stretch amplitude. Here, we investigate whether these trends continue with further increases in shortening or stretch amplitude. Experiments were performed using in situ cat soleus muscles (n=8 for FD; n=7 for FE and passive FE). FD, FE and passive FE were measured after shortening or stretch contractions that covered as wide a range of amplitudes as practically possible without damaging the muscles. FD increased approximately linearly with shortening amplitude, over the full range of amplitudes investigated. This is consistent with the hypothesis that FD arises from a stress-induced inhibition of crossbridges. FE increased with stretch amplitude only up to a point, and then levelled off. Passive FE, and the transient increase in force at the end of stretch, showed relationships to stretch amplitude that were qualitatively very similar to the relationship for FE, increasing only until the same critical stretch amplitude had been reached. We conclude that FE and passive FE do not increase with stretch amplitude under all circumstances. This finding has important consequences for determining the mechanisms underlying FE and passive FE because any mechanism that is proposed to explain them must be able to predict it.     

The sensitivity of Renshaw cells to velocity of sinusoidal stretches of the triceps surae muscle.

1. The electrical activity of Renshaw cells monosynaptically excited by ventral root stimulation and disynaptically excited by electric stimulation of the group I afferents in the GS nerve has been recorded and their response to individual sinusoidal stretches of the deefferented GS muscle tested for different amplitudes and durations of the stimulus. 2. The experimental data indicate that the Rensahw cell responses are not only length dependent but also rate dependent. This finding indicates that the same Renshaw cells receive recurrent collaterals of both tonic and phasic motoneurons. 3. The observation that the discharge of Renshaw cells is particularly sensitive to the velocity of stretch suggests that the recurrent collaterals of large phasic motoneurons, which are recruited during high velocity stretches, exert a stronger excitatory action on Renshaw cells than do axon collaterals of the smaller tonic motoneurons, which are selectively stimulated during low velocity stretches.     

Acoustic myography as an indicator of force during sustained contractions of a small hand muscle

To test the hypothesis that muscle sound amplitudes would remain constant during sustained submaximal isometric contractions, we recorded acoustic myograms from the abductor digiti minimi muscle in 12 subjects at 15, 25, 50, and 75% of a maximum voluntary contraction (MVC). Muscle sounds were detected with an omni-directional electret microphone encased in closed-cell foam and attached to the skin over the muscle. Acoustic amplitudes from the middle and end of the sustained contractions were compared with the amplitudes from the beginning of contractions to determine whether acoustic amplitudes varied in magnitude as force remained constant. Physiological tremor was eliminated from the acoustic signal by use of a Fourier truncation at 14 Hz. The amplitudes of the acoustic signal at a contraction intensity of 75% MVC remained constant, reflecting force production over time. At 50% MVC, the root-mean-square amplitude decreased from the beginning to the end of the contraction (P less than 0.05). Acoustic amplitudes increased over time at 15 and 25% MVC and were significantly higher at the end of the contractions than at the beginning (P less than 0.05). Alterations in the acoustic amplitude, which reflect changes in the lateral vibrations of the muscle, may be indicative of the different recruitment strategies used to maintain force during sustained isometric contractions.     

Response of Renshaw cells to sinusoidal stretch of hindlimb extensor muscles.

1. Renshaw cells responding disynaptically to electrically induced group I volleys in the intact gastrocnemius-soleus (GS) nerve, were submitted to small-amplitude, high-frequency vibration applied longitudinally to the deefferented GS muscle in precollicular decerebrate cats. 2. Vibration of the GS muscle at 200/sec, 180 mu peak-to-peak amplitude for 80-100 msec produced a sudden increase in the discharge rate of Renshaw cells, which gradually decreased within 25-50 msec to reach a steady level higher than that recorded in the absence of vibration. 3. Excitation of Renshaw cells appeared at a threshold amplitude of vibration (at 200-250/sec) of 5-20 mu and increased to a maximum value for amplitudes of about 70-80 mu, i.e., when all the primary endings of the spindles from the GS muscle had been driven by the stimulus. Recruitment of the secondary endings of the muscle spindles, due to large amplitude muscle vibration, did not modify the response of the Renshaw cells to the mechanically induced group Ia volleys. 4. These findings were obtained with the GS muscle pulled at 8 mm of initial extension. A threshold response of Renshaw cells to vibration appeared at 4 mm of static stretch, while maximal responses occurred at 8 mm. No further increase and actually a slight decrease in the response appeared for initial extensions of the muscle of 10-12 mm. 5. For a given vibration amplitude, the response of the Renshaw cells increased with increasing frequencies of vibration to reach the maximum at frequencies of 150-250/sec. Bursts of Renshaw cell discharges synchronous to each stroke of vibrator occurred only for low frequencies of stimulation (less than 25/sec). 6. It is concluded that vibration of the GS muscle represents a very effective method in exciting the Renshaw cells and that this response depends upon selective stimulation of homonymous motoneurons monosynaptically excited by the orthodromic volleys originating from the primary endings of the corresponding muscle spindles.     

Induction of apoptosis in vascular smooth muscle cells by mechanical stretch

We studied the response of porcine vascular smooth muscle cells (PVSMCs) to cyclic sinusoidal stretch at a frequency of 1 Hz. Cyclic stretch with an area change of 25% caused an increase in PVSMC apoptosis, which was accompanied by sustained activation of c-Jun NH(2)-terminal kinases (JNK) and the mitogen-activated protein kinase p38. Cyclic stretch with an area change of 7% had no such effect. Infection of PVSMCs with recombinant adenoviruses expressing constitutively active forms of upstream molecules that activate JNK and p38 also led to apoptosis. The simultaneous blockade of both JNK and p38 pathways with adenovirus-mediated expression of dominant-negative mutants of c-Jun and p38 caused a significant decrease (to 1/2) of the apoptosis induced by 25% cyclic stretch. The 25% stretch also caused sustained clustering of tumor necrosis factor-alpha (TNF-alpha) receptor-1 and its association with TNF-alpha receptor-associated factor-2 (TRAF-2). Overexpressing the wild-type TRAF-2 in PVSMCs caused an increase in apoptosis. In contrast, the expression of a dominant-negative mutant of TRAF-2 attenuated stretch-induced apoptois. These results support the hypothesis that circumferential overload under hypertensive conditions induces a clustering of death receptors that cause vascular smooth muscle cell apoptosis.     

Cerebellar cortical activity during stretch of antagonist muscles

Single unit activity was recorded from the anterior lobe of the cerebellum during ramp and hold stretches of limb muscles in chloralose anesthetized cats. The activity of 95 "phasic" units showed a transient response during dynamic stretch of at least one muscle usually lasting for less than 350 ms following the stimulus onset. The activity of 59 phasic-tonic units was modified not only during dynamic stretch but also during the 1 s of maintained muscle length. All Purkinje cells, identified by their complex spikes, that responded to muscle stretch demonstrated exclusively phasic changes in discharge. Fourteen of 25 Purkinje cells (56%) responded to stretch of both antagonist muscles and these responses were always similar rather than reciprocal. From the 129 units without complex spikes, 70 demonstrated phasic discharge patterns whereas 59 had tonic responses. Seventy-five (59%) of these unidentified units revealed convergent responses to stretch of both antagonists, compared with 54 which responded to stretch of one muscle only. Of the unidentified units receiving convergent afferents from antagonist muscles, 62 (83%) had similar responses and only 13 (17%) had reciprocal reactions. There appeared to be no evidence that muscle afferents alone can induce reciprocal discharge patterns in Purkinje neurons of the cerebellar cortex. The firing frequency of some phasic-tonic units was correlated with both the velocity and amplitude of muscle stretch. No Purkinje cells were found with activity related to either velocity or amplitude of muscle stretch. One phasic and seven phasic-tonic unidentified units were activated at fixed latencies following trains of electrical stimulation applied to the thoracic spinal cord at frequencies exceeding 200 Hz, implying they were terminal portions of mossy fibers originating from direct spinocerebellar tracts. A few recordings of compound potentials were presumed to arise from the cerebellar glomeruli. The changing form of one of these potentials suggested that the glomerulus might be a site at which somatosensory peripheral information is modified by the cerebellar cortex.