Unilateral suppression of pharyngeal motor cortex to repetitive transcranial magnetic stimulation reveals functional asymmetry in the hemispheric projections to human swallowing

Age-related physiological and morphological changes of muscle spindles were examined in rats (male Fischer 344/DuCrj: young, 4–13 months; middle-aged, 20–22 months; old, 28–31 months). Single afferent discharges of the muscle spindles in gastrocnemius muscles were recorded from a finely split dorsal root during ramp-and-hold (amplitude, 2.0 mm; velocity, 2–20 mm s⁻¹) or sinusoidal stretch (amplitude, 0.05–1.0 mm; frequency, 0.5–2 Hz). Respective conduction velocities (CVs) were then measured. After electrophysiological experimentation, the muscles were dissected. The silver-impregnated muscle spindles were teased and then analysed using a light microscope. The CV and dynamic response to ramp-and-hold stretch of many endings were widely overlapped in old rats because of the decreased CV and dynamic response of primary endings. Many units in old rats showed slowing of discharge during the release phase under ramp-and-hold stretch and continuous discharge under sinusoidal stretch, similarly to secondary endings in young and middle-aged rats. Morphological studies revealed that primary endings of aged rat muscle spindles were less spiral or non-spiral in appearance, but secondary endings appeared unchanged. These results suggest first that primary muscle spindles in old rats are indistinguishable from secondary endings when determined solely by previously used physiological criteria. Secondly, these physiological results reflect drastic age-related morphological changes in spindle primary endings.     

Responses of cat dorsal spino-cerebellar tract neurons to sinusoidal stretching of the gastrocnemius muscle

A defined class of cells within the nucleus dorsalis (Clarke's column) receives excitatory input from Ia afferents of mainly one muscle. Action potentials were recorded from axons of these cells (DSCT neurons) which are excited by Ia afferents of the gastrocnemius muscles. We investigated the response to sinusoidal muscle stretch over a wide range of amplitudes (10 m–4 mm) and frequencies (0.1–130 Hz) in the deefferented preparation. The dynamic stretch was superimposed on a moderate static muscle stretch to ensure that the muscle was not slack during the phase of release. The response up to 10 Hz was displayed as PST histograms (cycle histograms) and a sinewave of stretch frequency was fitted to the PST histograms to define amplitude and phase of a response sinewave.At a constant frequency of about 3Hz, the relation between stretch amplitude and response amplitude could well be described by decelerating intensity functions: the hyperbolic or tanh log function and a modified power function (exponent 0.48±0.12). The phase lead of the response sinewave increased with increasing stretch amplitudes of up to 0.5 mm and then decreased.At constant stretch amplitudes of 0.5–2.0 mm the frequency response was investigated. In relation to stretch frequencies between 0.1 and 1 Hz an increase in the response amplitude of 4.4dB was observed and an increase for 13dB/decade between 3 and 10 Hz. At 0.1 Hz the phase of the response sinewave was 48° in advance and increased to a maximum lead of 89° at 6–8Hz. Above 10Hz the positions of the responding action potentials with respect to the stretch cycle were used to define a phase, which was in advance up to 60 Hz but decreased and changed to a phase lag at higher frequencies.If in PST histograms no periods of silence occurred during the phase of stretch release, the mean discharge rate was found to be independent of the sinusoidal stretching. If the pauses were present the mean rate increased with increasing stretch frequencies or amplitudes.     

Alteration of proprioceptive messages induced by tendon vibration in man: a microneurographic study

Summary The activities of single proprioceptive fibres were recorded from the lateral peroneal nerve using transcutaneously implanted tungsten microelectrodes. Unitary discharges originating from muscle spindle primary and secondary endings and Golgi tendon organs were identified by means of various physiological tests. The sensitivity of proprioceptors to mechanical vibrations with a constant low amplitude (0.2–0.5 mm) applied at various frequencies to the tendon of the receptor-bearing muscle was studied. Muscle spindle primary endings (Ia fibres) were found to be the most sensitive to this mechanical stimulus. In some cases their discharge could be driven in a one-to-one manner up to 180 Hz. Most of them also fired harmonically with the vibration up to 80 Hz and then discharged in a subharmonic manner (1/2–1/3) with increasing vibration frequencies. Muscle spindle secondary endings (II fibres) and Golgi tendon organs (Ib fibres) were found to be either insensitive or only slightly sensitive to tendon vibration in relaxed muscles. The effects of tendon vibration on muscle spindle sensory endings response to muscle lengthening and shortening induced by imposed constant velocity or sinusoidal movements of the ankle joint were studied. Modulation of the proprioceptive discharge frequency coding the various joint movement parameters was either completely or partly masked by the receptor response to vibration, depending on the vibration frequency. Moreover, vibrations combined with sinusoidal joint movements elicited quantitatively erroneous proprioceptive messages concerning the movement parameters (amplitude, velocity). The sensitivity of the Golgi tendon organs to vibration increased greatly when the receptor-bearing muscle was tonically contracted. These data confirm that vibration is able to preferentially activate the Ia afferent channel, even when the vibration amplitude is low. They define the frequency sensitivity of the muscle spindle primary and secondary endings and the Golgi tendon organs. They also show that the physiological messages triggered by ongoing motor activities undergo a series of changes during the exposure of muscles to vibration.     

Analysis of response properties of deefferented mammalian spindle receptors based on frequency response.

Sinusoidal responses of primary and secondary endings in deefferented spindles of anesthetized cats were studied over the low-frequency range 0.001-0.1 Hz. Stretch amplitudes were chosen conservatively small (25-100 mum peak-to-peak) so as to lie within the linear region. 1. At 0.1 Hz average sensitivity was 350 pps/mm for primary endings and 80 pps/mm for secondary endings. Sensitivity fell to lower values at lower frequencies, but even at 0.001 Hz, corresponding to 17 min/cycle, sensitivity remained elevated above static values determined with large stretches. Phase lead varied from 5 to 50 degrees and, in the case of primary endings, tended to be greater at lower frequencies. 2. Except for the different scaling factors, the only apparent difference between the frequency responses of primary and secondary endings was a tendency for primary endings to show a greater phase lead over the range 0.001-0.01 Hz. 3. Dynamic responsiveness was assessed theoretically from frequency-response data by calculating responses to ramps at various velocities. Over most of the velocity range dynamic responses were not proportional to velocity. The greater dynamic responsiveness of primary endings during large (6 mm) ramp stretches might be related to frequency response below 0.01 Hz. 4. Certain aspects of dynamic responsiveness to large ramps (6 mm) were accounted for by assuming all phases of responses were attenuated by 25 dB in the case of primary endings and 20 dB in the case of secondary endings. The nonlinearity responsible for attenuation appears to occur at an early stage in the sensory process. 5. Comparison of individual responses to slow ramps with predictions based on linear theory indicated the presence of abrupt departures from linearity for both primary and secondary endings.     

Impulse activity and receptor potential of primary and secondary endings of isolated mammalian muscle spindles.

1. An isolated muscle spindle preparation from a tail muscle of cat is described. The afferent response to a ramp-and-hold stretch was recorded in individual axons from identified primary and secondary endings. 2. Primary endings exhibit a prominent dynamic response, including an initial burst. They also show a well-maintained static discharge. Secondary endings also show a well-sustained static discharge but generally have a much lower dynamic sensitivity. The response of primary and secondary endings of the isolated spindle are similar to the typical responses seen in vivo in groups Ia or group II afferent fibres respectively. 3. Following impulse blockade by tetrodotoxin, the receptor potential was recorded from primary and from secondary endings in response to ramp-and-hold stretch. 4. During the dynamic phase the receptor potential of primary endings consists of a depolarization which has two components. (a) An initial component occurs early during ramp stretch, depends in rate of rise and amplitude on velocity of stretch and is reduced on repetitive stretch; it appears to be responsible for the initial burst. (b) A late dynamic component, which follows, is also dependent on stretch velocity and produces the late dynamic discharge. At the end of ramp stretch the receptor potential falls, and may undershoot, the static level. There is a subsequent adaptive fall during hold stretch, then a maintained static level of receptor potential. On release from stretch the membrane is hyperpolarized. 5. Secondary endings usually show a smaller dynamic response, lacking the initial component seen in primary endings. They also generally lack an undershoot following the ramp and have less of a post-release hyperpolarization. 6. Static levels of receptor potential in both primary and secondary endings are related to amplitude of stretch. 7. The receptor potentials of primary and secondary endings account for the major features of the impulse responses of these endings to ramp-and-hold stretch. In primary endings the dynamic frequencies may also depend upon a sensitivity of the impulse initiating site to rate of change of receptor current.     

The relative sensitivity to vibration of muscle receptors of the cat

1. Longitudinal vibration was applied to the de-efferented soleus muscle of anaesthetized cats while recording the discharge of single afferent fibres from the proprioceptors within the muscle. Conditions were defined under which vibration can be used to excite selectively the primary endings of muscle spindles without exciting the secondary endings of muscle spindles or Golgi tendon organs.2. Frequencies of vibration of 100-500 c/s were used. The maximum amplitude of vibration which the vibrator could produce fell with increasing frequency; it was 250 mu (peak to peak) for 100 c/s and 20 mu for 500 c/s.3. Primary endings of muscle spindles were very sensitive to vibration. Most could be ;driven' to discharge one impulse for each cycle of vibration over the whole of the above range of frequencies, provided the initial tension was moderate (20-200 g wt.). The amplitude of vibration required to produce driving usually varied by less than a factor of two over the whole range of frequencies. The most sensitive endings could be driven by vibrations of below 10 mu amplitude.4. Stimulation of single fusimotor fibres, whether static or dynamic fusimotor fibres, increased the sensitivity of primary endings to vibration. Contraction of the main muscle, produced by stimulating alpha motor fibres, reduced the sensitivity of primary endings even when fusimotor fibres were also being stimulated.5. The secondary endings were very insensitive to longitudinal vibration and with the amplitudes available not one of twenty-five endings could be driven at 150 c/s or above; one ending could be driven at 100 c/s by vibration of 250 mu amplitude. Stimulation of single fusimotor fibres, probably all of which were static fusimotor fibres, made them slightly more sensitive to vibration but none of them approached the sensitivity of the primary endings.6. The Golgi tendon organs were as insensitive as the secondary endings when the muscle was not contracting and none could be driven at any frequency in spite of quite high tensions in the muscle. However, when the muscle was made to contract by stimulating alpha fibres in ventral root filaments the tendon organs became appreciably more sensitive, the degree of sensitization increasing approximately with the strength of the contraction. They never became as sensitive as the primary endings, and with the amplitudes of vibration available none was driven at frequencies of over 250 c/s.7. When the amplitude of vibration was somewhat below that required to produce driving of an ending it still produced some increase in its mean frequency of discharge. However, amplitudes of vibration of 25-50 mu applied to a non-contracting muscle, whether with or without fusimotor stimulation, produced driving of nearly all primary endings without any significant increase in the mean frequency of firing of secondary endings or Golgi tendon organs. Such vibration can therefore be used as a specific stimulus for the primary endings in order to investigate the central effects or repetitive discharge of the Ia afferent fibres from them.8. Experiments on endings in the peroneus longus muscle showed that these behaved similarly to those in soleus.     

The responses of human muscle spindle endings to vibration of non-contracting muscles.

1. In micro-electrode recordings from the human peroneal and tibial nerves, the responses of thirty-two primary spindle endings, thirteen secondary spindle endings and three Golgi tendon organs were studied during vibration of the tendons of the receptor-bearing muscles in the leg. The amplitude of the applied vibration was 1-5 mm and the frequency was varied from 20 to 220 Hz. As checked with e.m.g. and torque measurements, the muscles of the leg were relaxed during the sequences analysed. 2. Providing that the vibrator was accurately applied, all endings responded with discharges phase-locked to the vibration cycles, the discharge rates being at the vibration frequency or at subharmonics of that frequency. The response to vibration was of abrupt onset and offset, was maintained for the duration of vibration, and was not subject to fluctuation with changes in attention or with remote muscle contraction. 3. The maximal discharge rate that could be achieved varied from one ending to the next, and increased with the length of the receptor-bearing muscle. For endings driven at their maximal rate an increase in vibration frequency produced a decrease in discharge rates as the ending changed to a subharmonic pattern of response. The converse occurred on decreasing vibration frequency. 4. For any given muscle length, primary endings could generally be driven to higher rates than secondary endings but there was a wide range of responsiveness within each group and a significant overlap between the groups. At medium muscle length, the most responsive primary endings could be driven up to 220 Hz but secondary endings did not reach discharge rates higher than 100 Hz. 5. With combined vibration and passive movements, primary endings exhibited maximal vibration responsiveness during the stretching phases, sometimes firing twice per vibration cycle. During the shortening phases, however, they usually ceased responding to the vibratory stimulus. The vibration responsiveness of secondary endings was not potentiated to the same extent by on-going muscle stretch or reduced to the same extent by on-going muscle shortening. Thus, during shortening, secondary endings may be more responsive than primary endings. 6. The responses of primary endings to tendon taps were reduced during muscle vibration, a reduction which probably contributes to vibration-induced suppression of tendon jerks. Additionally, as the muscle shortened after tendon percussion, there was a transient pause in the response to vibration.     

Static and dynamic fusimotor action on the response of IA fibres to low frequency sinusoidal stretching of widely ranging amplitude

1. Single fusimotor fibres were stimulated repetitively to test their action on the responsiveness of muscle spindle primary endings in the cat soleus to sinusoidal stretching of both large and small amplitude. Frequencies of 0.06-4 Hz were used at amplitudes from 10 mum to 3 mm.2. The response was assessed by fitting a sinusoid to the cycle histogram of the afferent firing throughout the course of the cycle; this linear approximation measures the fundamental of the response and ignores any harmonics. The sine was allowed to project to negative values and any empty bins in the histogram were ignored when fitting.3. With small amplitudes of stretching the histograms were reasonably sinusoidal, but with large amplitudes they showed appreciable distortion of the wave form for the passive ending and during dynamic fusimotor stimulation. Non-linearity of response manifested itself also, with increasing amplitude of stretching, by an increase in the phase advance of the response, by increasing r.m.s. deviation of the histogram points from the fitted sine and (for dynamic stimulation) by an increase in the mean value of the fitted sine.4. With increasing amplitude the response modulation ceased to increase proportionately with the stimulus, so that the sensitivity of the ending to a large stretch (defined as afferent modulation/stretch amplitude) was appreciably less than for a small stretch. This effect was most pronounced for the passive ending.5. Whatever the amplitude of movement the modulation during static stimulation was less than that for the passive or during dynamic stimulation. For small amplitudes the response during dynamic stimulation was less than that of the passive, but for large amplitudes the response during dynamic stimulation was always the greater. At some intermediate cross-over amplitude the two responses were the same size, though still differing slightly in other respects. The value of the cross-over amplitude was usually about 200 mum at 1 Hz, and increased on lowering the frequency. Thus dynamic fusimotor action does not uniformly produce either an increase or a decrease in the sensitivity of the ending in relation to the passive.6. Bode plots, for each amplitude, of sensitivity and phase against frequency suggested that(a) under all conditions the ending is relatively insensitive to frequency in the range studied, for the slope of the log-log sensitivity lines was only 0.15-0.2 (3.5-6 db/decade);(b) the mechanism which makes for non-linearity is not particularly frequency sensitive;(c) static fusimotor stimulation does not change the frequency sensitivity of the ending;(d) dynamic fusimotor stimulation very slightly increases the frequency sensitivity of the ending for large amplitudes.In reaching these conclusions more attention was paid to the slope of the sensitivity lines than to the values of phase.7. It appears that the major effect of fusimotor action, whether static or dynamic, is to regulate the sensitivity of the primary ending to stretching for all amplitudes of movement (i.e. gain) rather than to control the relative values of its sensitivity to length and to velocity (i.e. crudely, the damping in a feed-back loop).     

Small-signal analysis of response of mammalian muscle spindles with fusimotor stimulation and a comparison with large-signal responses.

1. Response dynamics of primary and secondary muscle spindle endings to small-amplitude sinusoidal stretches were found to be unaltered by tonic repetitive stimulation of fusistatic or fusidynamic fibers. 2. Overall sensitivity of these receptors is decreased by fusistatic stimulation and either unchanged, increased, or decreased by fusidynamic stimulation at rates of 75/s or greater. 3. In the case of primary endings, the results obtained with small-amplitude sinusoidal stretches are not compatible with the response of these receptors to large-amplitude ramp stretches. The difference is explained by dependence of receptor dynamics on stretch amplitude. Fusistatic stimulation tends to prevent those changes in dynamics, whereas fusidynamic stimulation tends to enhance them. 4. In the case of secondary endings, the results obtained with small- and large-amplitude stretches appear to be compatible with a linear model for this receptor (i.e., one with dynamics independent of input parameters). 5. By modulating the frequency of stimulation applied to fusimotor fibers and comparing the resulting afferent response to the receptor response to stretch dynamic characteristics of intrafusal muscle contraction can be deduced. The results suggest that the dynamics of fusiastatic and fusidynamic contraction are the same and, furthermore, that they are the same as those of extrafusal muscle. We note that the result is incompatible with measurements of the time course of twitch and tetanus development and suggest, therefore, that muscle dynamics are a function of contractile state.     

Responses of isolated Golgi tendon organs of cat to sinusoidal stretch

1. Receptor potential and tension have been recorded from isolated Golgi tendon organs in response to sinusoidal stretch. Responses depended on amplitude and frequency of stretch and on the initial (resting) tension of the preparation. 2. Both tension and receptor potential behaved as power functions of stretch amplitude over most of the range corresponding to physiological tendon strains. However, for very small stretch amplitudes (less than 8 microns), a more linear response was seen. Those characteristics of responses that depended on stretch amplitude behaved similarly at all frequencies examined. 3. Frequency dependence of tension was slight. Its character, a gradual monotonic increase in response with increasing stretch frequency and a constant phase lead of a few degrees, did not change over the examined frequency range from 0.12 to 80 Hz. In contrast, receptor potential displayed a marked frequency dependence, increasing rapidly with increasing frequency of stretch in the range from approximately 1 to 20 Hz, then slowly declining as frequency was further increased. 4. Changes in initial tension of the preparation produced marked parallel changes in the amplitude dependence of tension and receptor potential. Frequency response was not significantly affected. 5. By comparing tension and receptor potential responses, the relative contributions of mechanical and electrical properties of the receptor to the sensory transduction process was examined. The present results suggest that in tendon organs the observed nonlinear dependence on amplitude of stretch originates primarily in the mechanical stage of transduction. Dynamic sensitivity, however, seems largely attributable to ionic processes within the sensory terminal membranes.     

Receptor potentials of isolated frog muscle spindle evoked by sinusoidal stimulation

Receptor potentials in response to sinusoidal stimulation have been recorded from isolated muscle spindles of the frog. Sinusoidal displacements of different amplitudes (20-120 micron) and frequencies (0.1-100 Hz) were used. The mean static stretch level was adjusted between resting length (L0) and L0 + 400 micron, so that the amplitude and phase-response characteristics were measured at different operating points. Depending on the amount of static prestretch, there is a well-defined dynamic range, which limits the receptor potential by nonlinear compression of either its positive or negative half-cycle. For each point on the static operating curve there exists a dynamic operating curve with a sigmoidal shape. The range of each dynamic curve is approximately 80 micron, independent of the static displacement, and the maxima of all dynamic curves are the same. Therefore the dynamic curves are not symmetrical about their static operating point. The slope of the steepest portion is 10% of the maximum elicitable receptor potential per 10-micron dynamic displacement. For stimulus frequencies greater than 2 Hz the receptor potential deviates from a sinusoidal waveform, exhibiting a fast depolarization transient during stretch and a prolonged repolarization transient during release of stretch. The steepness of the depolarization transient increases with increasing stimulus frequency, amplitude, and prestretch level. As a result, the interval from trough to peak of the receptor potential shortens to less than 90 degrees instead of half a cycle. The repolarization transient has an exponential decay with a time constant of approximately 40 ms that remains constant during the various stimulus conditions. As a result of this slow decay time, individual receptor potentials summate, so that the response divides into a modulated receptor potential (AC component) and a maintained depolarization (DC component). The amplitude response characteristic of the stationary AC component increases with increasing stimulus frequencies up to a peak at 2 Hz, after which it declines with a slope of -3 dB/octave. Provided large sinusoidal stretches and/or extended prestretch levels are used, this high-frequency decline of the AC component is compensated for by the proportional increase of the DC component, so that the peak depolarization values remain constant from 2 to 100 Hz. Stimulus and response are in phase for stimulus frequencies less than 2 Hz and reverse to phase lag at higher stimulus frequencies.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characterization of spindle afferents in rat soleus muscle using ramp-and-hold and sinusoidal stretches

The discharge properties of 51 afferents were studied in the rat soleus muscle spindles. Under deep anesthesia using a pentobarbital sodium solution (30 mg/kg), a laminectomy was performed and the right L(4) and L(5) dorsal and ventral roots were transected near their entry into the spinal cord. In situ, the minimal (L(min)) muscle length [3 +/- 0.08 (SE) cm] of the soleus was measured at full ankle extension. Unitary potentials from the L(5) dorsal root were recorded in response to ramp-and-hold stretches applied at 3 mm (S3) and 4 mm (S4) amplitudes and four stretch velocities (6, 10, 15, and 30 mm/s), sinusoidal stretches performed at four amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch frequencies (0.5, 1, 2, 3, 6, and 10 Hz), and vibrations applied at 50-, 100-, and 150-Hz frequencies. These two kinds of stretches were performed at three different muscle lengths (L(min+10%), L(min+15%), and L(min+20%)), whereas vibrations were applied at L(min+20%) muscle length. Conduction velocity of the fibers was calculated but did not allow to discriminate different fiber types. However, the mean conduction velocity of the first fiber group (43.3 +/- 0.8 m/s) was significantly higher than that of the second fiber group (33.9 +/- 0.9 m/s). Three parameters allowed to differentiate the responses of primary and secondary endings: the dynamic index (DI), the discharge during the stretch release from the ramp-and-hold stretches, and the linear range and the vibration sensitivity from sinusoidal stretches. The slope histogram of the linear regression based on the DI and the stretch velocity was clearly bimodal. Therefore the responses were separated into two groups. During the stretch release at a velocity of 3 mm/s, the first response group (n = 26) exhibited a pause, whereas the second (n = 25) did not. The linear range of the second ending group (0.12-1 mm) was broader than that of the first (0.12-0.25 mm). The first ending group showed a higher sensitivity to high-vibration frequencies of small amplitude than the second. In comparison with the literature, we can assert that the first and the second ending groups corresponded to the primary and secondary endings, respectively. In conclusion, our study showed that in rat soleus muscle spindles, it was possible to immediately classify the discharge of Ia and II fibers by using some parameters measured under ramp-and-hold and sinusoidal stretches.     

A model of spindle afferent response to muscle stretch

1. A unified model of the properties of stretch responses of mammalian spindle endings is proposed. This model encompasses the disparity between sensitivity of spindle endings to small and to large stretch of the muscle as well as the disparity in their dynamic responsiveness for different amplitudes of stretch. 2. In the model the mechanical properties of intrafusal fibers include a property akin to friction, which is hypothesized on the basis of reported observations on amphibian muscle. Transducer and encoder processes are modeled in the light of recent observations on isolated spindles. The model involves five unknown parameters whose values are selected by reference to certain reported observations on deefferented primary and secondary endings. The model can be used to predict responses to length changes of arbitrary time course. 3. Predicted responses to large ramp-and-hold stretch are quantitatively comparable to observations over a wide range of stretch velocities. The quantities compared include the increment in response during ramp stretch as well as the dynamic index, which is a measure of adaptation at stretch plateau. 4. At a fixed frequency of sinusoidal stretch, the relation between amplitudes of stretch and response is predicted in quantitative agreement with measurements. As the frequency of stretch is decreased, the predicted phase lead decreases and then increases, while the sensitivity decreases monotonically, in accord with observations. 5. In the model the high sensitivity for small stretch is not specific to any particular length of the muscle. When stretch is large, the region of high sensitivity is gradually reestablished at the new length, a phenomenon referred to as resetting. The dynamic response to a large stretch can be seen as arising, for the most part, from the dynamic process of resetting. 6. The influences of static or dynamic fusimotor activation on stretch responses of the primary ending are simulated by modifying the parameter values in the model. The modifications are such that static (dynamic) fusimotor activity speeds up (slows down) the resetting of the high-sensitivity region. The predictions mimic qualitatively the observed fusimotor effects not only on the response to large ramp stretch but also the contrasting effects seen with smaller, sinusoidal stretch.     

Responses of neurones in motor cortex and in area 3A to controlled stretches of forelimb muscles in cebus monkeys.

1. The experiments were designed to investigate the effects of longitudinal muscle displacements on neurones of the motor cortex of anaesthetized Cebus monkeys and thus test the hypothesis that signals from muscle spindles may modify motor cortical output. The effects of sinusoidal stretching of the extensor digitorum communis (EDC) at frequencies varying from 6 to 300 Hz and of step and rhomboidal stretches were studied in neurones of the motor cortex. For comparison, neurones of the primary receiving area for low-threshold muscle afferents, cortical area 3a, were also included in this study. Neurones of the motor cortex were subdivided into corticospinal (PT) neurones and non-corticospinal (non-PT) neurones. 2. Threshold stretch amplitudes were clearly higher for neurones of area 4 (PT and non-PT) than for 3a neurones. However, a conspicuous fall in threshold stretch amplitude was observed for all three neurone populations when the frequency of sinusoidal stretching was increased (highest frequency: 300 Hz). A small number of non-PT and PT neurones responded to vibration amplitudes of less than 100 mum and some of these low-threshold cells of area 4 also responded to rhomboidal stretches of 8 mm/sec ramp velocity and 80 mum plateau amplitude. Increasing the stretch amplitude to twice threshold nearly doubled the output magnitude in all three cell types. Neurones of area 3a and non-PT neurones of area 4 had similar latencies, and these were significantly shorter than the latencies of PT neurones tested with trains of high frequency vibration. Dynamic response patterns were observed in all three cell types, but most frequently in 3a neurones. 3. It is concluded that, in Cebus monkeys, signals from both primary and secondary muscle spindle endings from forelimb muscles reach the motor cortex. Under the present experimental conditions, the input from the primaries to the motor cortex was effective only if these spindle receptors were driven maximally by vibratory stimuli. The particularly low probability of stretch-evoked discharges of cortico-spinal neurones in the anaesthetized preparation may be explained by a low gain in transmission from input to output cells of the motor cortex.     

Transition in sensitivity of spindle receptors that occurs when muscle is stretched more than a fraction of a millimeter.

We studied the responses of 34 deefferented spindle receptors to slowly applied ramp stretches (0.01-1 mm/s) of small (0.02-0.2 mm) and intermediate (0.2-1 mm) amplitudes. The afferent discharge from primary and secondary endings was recorded from filaments of dorsal root in anesthetized cats. 1. Responses of most endings to ramps of intermediate amplitude showed abrupt changes in slope (discontinuities) which were highly repeatable. Discontinuities occurred more nearly at constant stretch (in the range 50-400 mum for different receptors) than at constant discharge rate. They were less pronounced in the case of secondary endings. 2. Changes in sensitivity occurred when the degree of stretch exceeded a transitional amplitude which ranged from 50 to 200 mum. These changes were studied by constructing plots based on a family of responses to a family of ramps which were scaled versions of each other. The plots indicated that reductions in sensitivity occurred both during stretch and during adaptation; the reductions were more marked for primary than for secondary endings. 3. Responses were modified considerably by preceding changes in muscle length. When the last change was an increase of a few millimeters, discontinuities became more pronounced and other changes in the appearance of the dynamic response occurred, particularly in the case of primary endings. These changes could last for several minutes, but were abolished by a single test stretch of intermediate amplitude. 4. The resetting of high sensitivity that occurs when muscle length is changed, the discontinuities, the transitions in sensitivity, nonlinear adaptation, and the effects of previous length change appeared to be related phenomena. They can all be accounted for by the hypothesis that polar zones of intrafusal muscle fibers possess a frictionlike property, one analogous to that which has been described for whole muscle. A simple nonlinear model which shows these features is presented. 5. The adequate stimulus for a change in primary ending discharge is a small change in muscle length, relatively independently of its velocity. The dynamic response arises mainly from a changing sensitivity to length itself, which is a nonlinear property.     

An analysis of muscle spindle behavior using randomly applied stretches

The behavior of mammalian muscle spindles to relatively large amplitude randomly applied stretches is compared to the linear behavior elicited by small amplitude sinusoidal stretches. The results disclose two apparently independent sources of nonlinear behavior. One is a static nonlinearity affecting both primary and secondary endings in which the sensitivity decreases with stretch amplitude up to about 1% stretch. The other is a ‘dynamic’ nonlinearity affecting only primary endings that is manifest as a charge in the ratio of rate to proportional sensitivity depending on the duration of an applied stretch.     

The response to stretch of human intercostal muscle spindles studied in vitro.

1. The discharge properties of human muscle spindles have been studied in vitro in a preparation based on the biopsied external intercostal muscle. 2. The static and dynamic responsiveness of thirty-six endings in twenty visualized and histologically identified spindles have been investigated using amplitudes and velocities of stretch likely to encompass those occurring in vivo. 3. The dynamic index, measured at a stretch velocity of 3 mm/sec, ranged from 3 to 40 impulses/sec and was distributed bimodally, consitent with the presence of primary and secondary endings. 4. The relationship between the dynamic index and the velocity of stretch was approximately linear both for primary and secondary endings up to the maximum velocity tested (10 mm/sec). 5. The frequency/extension relationship was approximately linear for both primary and secondary endings. The mean values of the slope for primary and secondary endings were 16-1 +/- 8-3 S.D. of the observation and 12-1 +/- 6-5 impulses/sec per five per cent extension. 6. The slopes of the frequency/extension relationship for endings lying in the same spindle were positively correlated, significant at the 10% level. 7. It was estimated from the results in vitro that the position sensitivity of human intercostal spindles in vivo ranges from 2 to 21 impulses/sec per millimetre.     

Facilitation effect of auxiliary noise stimuli on response of isolated frog muscle spindle to sinusoidal movements

Receptor potentials and impulse patterns were recorded from isolated frog muscle spindles using sinusoidal and superimposed random stretches as stimuli with different sinus-to-noise ratios. The entire dynamic amplitude range of the spindle receptor was evaluated by measuring the sensory response at different levels of static stretch. Auxiliary random stimuli provoked rectified fast depolarizing receptor potential transients; their amplitude and slope grew larger with increasing intensity of the noise stimulus and with increasing prestretch level. Due to this strongly nonlinear behavior of the transducing site the frequency and size of the receptor potentials evoked by the auxiliary input signal increased during the stretching phase of the sinusoidal movement. Since the fast depolarizing receptor potential transients provided a powerful trigger for the action potential encoding site, auxiliary random stimuli effectively enhanced the afferent discharge rate, especially during the stretching phase of the sinusoidal movement. Auxiliary noise stimuli could even activate the afferent discharge to an otherwise subthreshold sinusoidal stretch. It is assumed that by the same mechanism the transfer characteristic of the receptor is broadened towards higher frequencies. Since auxiliary random stimuli increased the nonlinear properties of all receptor response components, a "linearizing" approximation technique only partially describes the receptor's transfer properties. The facilitation effect recorded in the differentiated muscle spindle when random stimuli were superimposed on sinusoidal displacements closely resembled the excitation of afferent firing when passive stretching interacted with active fusimotor innervation. A hypothesis is proposed to explain both effects by the same mechanism acting upon the transducing sensory endings: Since passive random stretches as well as active twitching of the intrafusal muscle fibers exhibited almost the same range of frequency components, we propose that both stimuli also generate the same kind of receptor potentials; namely, those fast-rising depolarization transients of the receptor potential, which vigorously drive the encoding site. In general, these experiments explain how the specific response of a neuron can be facilitated by an additional unspecific (noisy) input.     

The effects of muscle cooling and stretch on muscle spindle secondary endings in the cat.

1. The objectives of the investigation were to identify the muscle spindle endings which respond to cooling of the relaxed muscle and to study their response to stretch. 2. The discharge of single afferents from 162 de-efferented muscle spindles in the relaxed medial gastrocnemius muscle of the anaesthetized cat was studied in vivo during cooling of the muscle from 37 to 24 degrees C. Temperature measurements were made at the inner surface of the muscle, while cooling (never below 15 degrees C) was applied at the skin over the muscle. 3. The endings were classified as primary or secondary endings on the basis of their conduction velocity, the dividing line being set at 70 m/sec. A response to cooling was obtained only from endings with afferents conducting at velocities of 20-70 m/sec. These fifty-six endings (CR) represented 65% of the secondary endings studied; the remaining secondary endings (NCR) and the primary endings showed no activity during cooling of the relaxed muscle. 4. During maintained stretches of 4-12 mm, activity of the NCR and primary endings decreased when the muscle was cooled. Cooling affected the CR endings in the same way, but only if the muscle was stretched 6 mm or more. During a smaller maintained muscle stretch, cooling caused an increase in CR activity, superimposed on the response to stretch. 5. The response to a 10 mm stretch at velocities of 10-70 mm/sec was studied in twenty-six CR, eleven NCR and twenty-one primary endings. 6. The dynamic responses of CR endings were intermediate between those of the primary endings and NCR endings. For any velocity of stretch the mean dynamic index of the CR endings was significantly greater than that of the NCR endings but significantly less than that of the primary endings. 7. The mean static responses of the CR and primary endings, measured 0-5 sec after the end of ramp stretch, were the same and significantly greater than that of the NCR endings. 8. The results indicate that cooling of the relaxed mammalian muscle may be used to differentiate between primary endings and about two-thirds of the secondary endings. The remaining secondary endings can be recognized by their small dynamic and static response to stretch.     

Reflex responses of gamma motoneurones to vibration of the muscle they innervate.

1. High frequency vibration was applied to the tendon of the non-contracting triceps surae muscle while recording the background discharges of single gamma fibres only small nerve bundles were cut, leaving most of the nerve supply to the triceps intact. 2. 22% out of a total of sixty-three gamma efferents were tonically inhibited by vibration. The inhibition appeared between 25 and 50mum peak-to-peak amplitude of vibration and increased to a plateau for amplitudes of about 100mum. The dependence of the tonic vibration reflex of alpha-efferents on the amplitude of vibration was found to be similar. Increasing the frequency of vibration from 150 to 300 Hz increased the degree of inhibition. 3. 33% of the fusimotor neurones investigated responded to muscle vibration with an increase in discharge rate. The threshold amplitudes of this reflex ranged from 20 to 50mum. Some features of the reflex, in particular the parallel post-vibratory facilitation found in alpha and gamma efferents, pointed to a polysynaptic pathway organized in an alpha-gamma linkage. 4. All gamma efferents inhibited by vibration showed inhibitory responses to antidromic stimulation of the parent ventral root, and most of them were inhibited by ramp stretch of the triceps. The gamma motoneurones facilitated by vibration, however, were excited by muscle stretch and were less susceptible to antidromic inhibition, some lacking it completely. 5. Cutting the nerves to triceps abolished the inhibitory as well as the excitatory responses of gamma efferents to muscle vibration. Both fusimotor reflexes were preserved after spinal section and subsequent administration of L-DOPA. 6. It is concluded that both of the fusimotor reflex effects of vibration are caused by excitation of primary spindle endings within the triceps. The inhibition of fusimotor neurones is thought to be mediated by Renshaw cells activated during vibration. The significance of positive feed-back on to gamma motoneurones as a result of autogenetic facilitation by Ia afferents is discussed in connexion with stability in the stretch reflex loop.