Time coupling of skeletomotor discharges in response to pseudo-random transsynaptic and transmembrane stimulation

Firing pattern of skeletomotor neurones innervating triceps surae muscles in response to pseudorandom muscle stretching and white noise modulated transmembrane current stimulation was investigated in decerebrate cats. Pseudo-random muscle stretching (upper cut-off frequency 60 Hz, amplitude (standard deviation) ranging from 18.5 m to 40 m) was applied to triceps surae muscles. Membrane potential changes and action potentials of skeletomotor neurones were recorded intracellularly. White noise modulated current was applied through the same (recording) microelectrode. Sequences of ten identical 5 s periods of either muscle stretching or transmembrane current stimulation were applied. Skeletomotor neurones belonging to slow motor units (rheobase less than 8.5 nA) generated action potentials in response to both pseudo-random muscle stretching and transmembrane current stimulation, while firing threshold of those belonging to fast motor units could not be reached by the muscle stretches applied. Peri-spike averaging of muscle length and injected current records showed that the action potentials appeared at the peak of either depolarizing current wave or muscle stretching both preceded by a change in opposite direction (the spikes coinciding with the peak in muscle length PSA being actually elicited by muscle spindle action potentials triggered at the moment of the peak stretching velocity). Time coupling of action potentials occurred during both muscle stretching and transmembrane stimulation, being more tight in the latter case as well as when larger amplitudes of the stimuli were applied. It is supposed that discharges from muscle spindle primary endings phase-locked to small pseudo-random muscle length changes may, due to the time coupling of skeletomotor action potentials, provoke a synchronous firing of skeletomotor neurones, mostly of those belonging to slow motor units. Possible effects of such a firing pattern on the resulting muscle reflex contraction and the stretch reflex stability as well as a possibility of it being provoked by fusimotor discharges are discussed.     

Spike activity of mesencephalic neurons during nociceptive stimulation of the alert cat

Rate of reorganizations of neuronal impulse activity in the ventromedial parts of the midbrain of alert rats in conditions of nociceptive and non-nociceptive actions is determined by biological value of used stimuli and closely correlates with spontaneous and evoked changes of the motor activity and oscillations of vegetative parameters. The character of reorganizations of discharge activity (activation, inhibition) significantly differs in cells of various types, singled out on the basis of differences of electrophysiological properties and predominantly localized in different parts of the studied brain areas. The revealed characteristics of the functional properties of the neurones are discussed in connection with supposed differences of their neurotransmitter specificity and their role in providing for different chains of adaptive activity of the organism.     

Correlations of neuronal spike discharges of VL neurons during spontaneous firing and during the activity evoked by peripheral stimulation

The temporal relations between simultaneously recorded neurons of the nucleus ventralis lateralis (VL) of cat thalamus were studied. The interaction and the functional connections between individual VL neurons are described. This was achieved with an application of cross correlation techniques. The response patterns of different individual neurons to somatic sensory and photic stimuli were also analyzed. For the purpose of classifying neurons as thalamocortical relay cells (T-C) and non relay cells (N-C) which do not project to the motor sensory cortex antidromic cortical stimulation was used. This stimulation was also used as conditioning one when proceeded peripheral stimuli. To analyze the nonspecific specific interactions upon single neurons conditioning photic stimuli were applied. The results show that T-C neurons are antidromically excited from a wide cortical areas and that the functional interaction between T-C neurons is mediated by a shared input from common sources. It is further postulated that N-C cells interposed between relay neurons subserve the functions of gating units modifying the neuronal network of lateral ventral nucleus of the thalamus.     

Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle

We directly measured cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA) in cats decerebrated at the level of the precollicular-premammillary body while the hindlimb or the triceps surae muscle was passively stretched. CVNA gradually decreased during passive stretch of the hindlimb, and this decrease was sustained throughout the stretch. CSNA increased at the onset of passive stretch, but this increase was not sustained. CVNA and CSNA responded differentially to graded passive stretches of the triceps surae muscle as well as the hindlimb. The sustained decrease in CVNA but not the initial increase in CSNA became greater depending on muscle length and developed tension. The time course and direction of the cardiac autonomic responses to muscle stretch were not affected by partial sinoaortic denervation, although the magnitude of the CSNA response was augmented. We conclude that the muscle mechanoreflex contributes to differential regulation of cardiac parasympathetic and sympathetic efferent discharges during passive stretch of skeletal muscle irrespective of arterial baroreceptor input.     

Morphological effects of electrical stimulation and intermittent muscle stretch after immobilization in soleus muscle

The objective of the present study was to assess the effectiveness of a combined protocol of muscle stretching and strengthening after immobilization of the hindlimb. Thirty female Wistar rats were divided into 6 groups: group immobilized for 14 days to cause full plantar flexion by cast (GI, n = 6); group immobilized/stretched (GIS, n = 6): submitted to the same immobilization and to 10 days of passive stretching; group immobilized/electrically stimulated (GIES, n = 6): similarly immobilized and submitted to 10 days of low frequency electrical stimulation (ES); group immobilized/stretched/electrically stimulated (GISES, n = 6): similarly immobilized, submitted to 10 days of stretching and ES application; group immobilized/free (GIF, n = 3): similarly immobilized and then left with free limbs for 10 days; control group (CG, n = 3). The middle portion of the soleus muscle was frozen and sections were stained with HE or mATPase. Morphological analysis revealed high cellular reactivity in the GISES, GIES and GIS groups. The lesser diameter and proportion of type I fibers (TIF) and type II fibers (TIIF) (at pH 9.4) and connective area (at HE stain) were measured with an image analyzer and the data obtained were analyzed statistically by the unpaired Student t-test (p < or = 0.05). The results indicated that: a) immobilization generated atrophy of both fiber types (p < 0.05); b) joint application of ES and stretching was not efficient in reestablishing the size of the two fiber types compared to CG (p < 0.05); c) the ES protocol reestablished only the size of TIIF, which showed values similar to those detected in CG (p < 0.05); d) the stretch increased the proliferation of the perimysium connective tissue (p < 0.05). Thus, we conclude that, in the model applied here to female rats, a stretching protocol may limit the volume protein gain of soleus muscle fibers and increase the connective interstitial tissue.     

Superimposing noise linearizes the responses of primary muscle spindle afferents to sinusoidal muscle stretch

Experiments were conducted in anaesthetized and spinalized cats to measure the extent to which the non-linear response of Ia afferent fibers to sinusoidal muscle stretch as expressed by the peristimulus-time-histograms, PSTHs, can be transformed into a linear one by means of the superposition of random stretch ("mechanical noise"). The gastrocnemius muscles of one hind leg were stretched and the response to sinewave muscle stretch (amplitudes between 0.01 and 4.0 mm, frequencies between 0.1 and 20 Hz) were investigated while band-limited mechanical noise was superimposed on the sinewave stretch. The random stretch upper cut-off frequency was varied between 60 and 300 Hz; the displacements were normally distributed. The noise amplitude sigma, i.e. the standard deviation of the displacement distributions, was varied systematically between 0.002 and 0.4 mm. Mechanical noise was very effective in raising the mean discharge rate. Added to the sinusoidal stretch it prevented the cessation of firing during the release phase of the stretch cycle, or at least reduced the duration of discharge pauses, i.e., a linearization occurred. In general, the larger the noise amplitude, the more the amplitude of the fundamental harmonic component was attenuated and the phase lead reduced. Apart from this rule the particular combination of superimposing small noise (sigma less than 0.02 mm) on small sinewave stretch (A less than 0.02 mm) could enhance the depth of sinusoidal modulation of cycle histograms (compared with responses to pure sinusoids). Linearizing the sinewave response by additional noise allowed the estimation of frequency response characteristics in the otherwise non-linear range of amplitudes (sinewave amplitude 0.5-1.0 mm).(ABSTRACT TRUNCATED AT 250 WORDS)     

Membrane potential changes of skeletomotor neurons in response to random stretches of the triceps surae muscles in decerebrate cats

 The properties of membrane potential changes of skeletomotor neurons (S, FR, and FF) innervating triceps surae muscles during pseudorandom stretching of these muscles were studied in decerebrate cats. Peak amplitudes of pseudorandom muscle stretches ranged from 119 μm to 4.15 mm peak-to-peak. Sequences of ten identical stretching periods were applied for averaging. Shapes of membrane potential changes and probability density distribution of amplitudes of the input and output signals and power spectra suggest that the skeletomotor neuron membrane has nonlinear properties. First- and second-order Wiener kernels were determined by applying the cross-correlation (Lee-Schetzen) method. The results suggest that the transfer function between muscle stretches and subthreshold membrane potentials is a Wiener-type cascade. This cascade is consistent with a linear, second-order, underdamped transfer function followed by a simple quadratic nonlinearity [linear (L) system followed by nonlinear (N) system, or LN cascade]. Including the nonlinear component calculated from the second-order Wiener kernel improved the model significantly over its linear counterpart, especially in S-type motoneurons. Qualitatively similar results were obtained with all types of motoneurons studied. Received: 1 April 1993/Accepted in revised form: 24 March 1994     

Third-order reverse correlation analysis of muscle spindle primary afferent fiber responses to random muscle stretch

The response of primary muscle spindle afferent fibers to muscle stretch is nonlinear. Now spindle responses (trains of action potentials) to band-limited Gaussian white noise length perturbations of the gastrocnemius muscles (input signal) are described in cats. The input noise upper cutoff frequency was clearly above the frequency range of physiological length changes in cat hindleg muscles. The input-output relation was analyzed by means of peri-spike averages (PSAs), which could be shown to correspond to the kernels of Wiener's white noise approach to systems identification. The present approach (the reverse correlation analysis) was applied up to the third order. An experiment consisted of two recordings: one (the source recording) to determine PSAs and the other (the test recording) to provide an input signal for predicting responses. The predictions of different orders were compared with the actual neuronal response (the observation) of the test recording. Four different approximation procedures were developed to adapt prediction and observation and to determine weighting factors for the predictions of different orders. The approximations also yielded the value of the power density P of the input noise signal: at a variety of stimulus parameters, P from approximations had the same magnitude as P determined directly from the input signal amplitude spectrum. The prediction of a sequence of action potentials improved the higher the order of components. 37 of 42 action potentials of a test recording (the observation) could be confidently predicted from PSAs or kernels. Compared with the size of the linear first-order prediction curve, the relative sizes of the second and third-order prediction curves were: 1.0∶0.47∶0.26.     

Third-order reverse correlation analysis of muscle spindle primary afferent fiber responses to random muscle stretch

 The response of primary muscle spindle afferent fibers to muscle stretch is nonlinear. Now spindle responses (trains of action potentials) to band-limited Gaussian white noise length perturbations of the gastrocnemius muscles (input signal) are described in cats. The input noise upper cutoff frequency was clearly above the frequency range of physiological length changes in cat hindleg muscles. The input–output relation was analyzed by means of peri-spike averages (PSAs), which could be shown to correspond to the kernels of Wiener’s white noise approach to systems identification. The present approach (the reverse correlation analysis) was applied up to the third order. An experiment consisted of two recordings: one (the source recording) to determine PSAs and the other (the test recording) to provide an input signal for predicting responses. The predictions of different orders were compared with the actual neuronal response (the observation) of the test recording. Four different approximation procedures were developed to adapt prediction and observation and to determine weighting factors for the predictions of different orders. The approximations also yielded the value of the power density P of the input noise signal: at a variety of stimulus parameters, P from approximations had the same magnitude as P determined directly from the input signal amplitude spectrum. The prediction of a sequence of action potentials improved the higher the order of components. 37 of 42 action potentials of a test recording (the observation) could be confidently predicted from PSAs or kernels. Compared with the size of the linear first-order prediction curve, the relative sizes of the second and third-order prediction curves were: 1.0 : 0.47 : 0.26. Received: 15 November 1994/Accepted in revised form: 23 May 1995     

Molecular dynamics of alamethicin transmembrane channels from open-channel current noise analysis.

Conductance noise measurement of the open states of alamethicin transmembrane channels reveals excess noise attributable to cooperative low-frequency molecular dynamics that can generate fluctuations approximately 1 A rms in the effective channel pore radius. Single-channel currents through both persistent and nonpersistent channels with multiple conductance states formed by purified polypeptide alamethicin in artificial phospholipid bilayers isolated onto micropipettes with gigaohm seals were recorded using a voltage-clamp technique with low background noise (rms noise < 3 pA up to 20 kHz). Current noise power spectra between 100 Hz and 20 kHz of each open channel state showed little frequency dependence. Noise from undetected conductance state transitions was insignificant. Johnson and shot noises were evaluated. Current noise caused by electrolyte concentration fluctuation via diffusion was isolated by its dependence on buffer concentration. After removing these contributions, significant current noise remains in all persistent channel states and increases in higher conductance states. In nonpersistent channels, remaining noise occurs primarily in the lowest two states. These fluctuations of channel conductance are attributed to thermal oscillations of the channel molecular conformation and are modeled as a Langevin translational oscillation of alamethicin molecules moving radially from the channel pore, damped mostly by lipid bilayer viscosity.     

Series elasticity in frog sartorius muscle during release and stretch

When a stretch is applied to an isolated muscle during tetanic stimulation, the force developed is higher than the maximal isometric tension (Po). This force puts the series elastic component (SEC) under tension and in a domain which is not well defined in terms of tension-extension curve. In the present work, an attempt was made to determine the stiffness of the SEC for tensions greater than Po, using the sartorius muscle of the frog. For this purpose, rapid releases and stretches of different amplitudes were given during maximal isometric contractions. Plotting normalized tension (P/Po) against normalized length changes (negative or positive extensions, delta L/Lo.10(2] produced a tension-extension curve. The slopes of the linear part of each relationship on both sides of Po indicated an increase in SEC stiffness when the muscle was rapidly stretched. Furthermore, the transient character of the increase in stiffness was studied by measuring SEC stiffness during rapid releases applied at various time intervals after stretches: the muscle was found to be stiffer as the time interval was shorter. The results are discussed in terms of (i) non-linear behaviour of the passive and active parts of the SEC, (ii) enhancement of storage and release of potential energy.     

Mechanical properties of rabbit latissimus dorsi muscle after stretch and/or electrical stimulation

James, R. S., V. M. Cox, I. S. Young, J. D. Altringham, andD. F. Goldspink Mechanical properties of rabbit latissimus dorsimuscle after stretch and/or electrical stimulation.J. Appl. Physiol. 83(2): 398-406, 1997.The work loop technique was used to measure the mechanicalperformance in situ of the latissimus dorsi (LD) muscles of rabbitsmaintained under fentanyl anesthesia. After 3 wk of incrementallyapplied stretch the LD muscles were 36% heavier, but absolute poweroutput (195 mW/muscle) was not significantly changed relative to thatof external control muscle (206 mW). In contrast, continuous 10-Hzelectrical stimulation reduced power output per kilogram of muscle>75% after 3 or 6 wk and muscle mass by 32% after 6 wk. Whencombined, stretch and 10-Hz electrical stimulation preserved orincreased the mass of the treated muscles but failed to prevent an 80%loss in maximum muscle power. However, this combined treatmentincreased fatigue resistance to a greater degree than electricalstimulation alone. These stretched/stimulated muscles, therefore, aremore suitable for cardiomyoplasty. Nonetheless, further work will benecessary to find an ideal training program for this surgicalprocedure.

     

The mechanical response of active human muscle during and after stretch

Five subjects contracted forearm supinator muscles which were stretched after development of maximal isometric torque. The ratio of torque at the end of stretch over isometric torque at that position was calculated as excess torque. Excess torque increased with stretch velocity and decreased with stretch amplitude, and it was not dependent upon final muscle length. The rate of decay of torque following stretch could not be shown to depend upon stretch variables. The absence of significant changes in myoelectric activity suggested that with high initial forces, reflex activity did not account for the observed changes. Time-constants of decay (0.15 s to 1.8 s) were much greater than time-constants of rise (approx. 0.07 s) of isometric torque at the same muscle length. This indicates that interaction of series elastic and contractile elements is not the sole cause of prolonged torque following stretch. It is concluded that stretch temporarily enhances the intrinsic contractile properties of a group of human muscles in a manner similar to, but quantitatively different from that seen in isolated muscle preparations.     

Analysis of evoked discharges in hypothalamic neurons to somatosensory,acoustic, and photic stimulation

Single unit activity in the supramammillary, mammillary, and anterior hypothalamic areas in response to acoustic, photic, and sciatic nerve stimulation was recorded in cats anesthetized with chloralose and immobilized with succinylcholine. In response to sensory stimulation the spontaneous firing rate was increased or decreased, and silent neurons were activated. Evoked potentials of the silent neurons had the shortest latent period to acoustic and somatosensory stimulation (15 msec), and rather longer to photic stimulation (30 msec); in some cases their latent period was 200 msec. Histograms of interspike interval distribution showed a maximum for intervals of up to 50 msec. Histograms of spike distribution relative to the beginning of stimulation showed maximal density between 100 and 200 msec. A high degree of convergence of excitation was found on units of the anterior as well as the posterior hypothalamus. Unit responses in the hypothalamus to sensory stimuli of all three modalities are regarded as being of secondary, nonspecific type.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 6, pp. 592–598, November–December, 1971.     

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.