Discharge Of Muscle Spindle Afferents Research Articles

English

The fundamental pattern of chewing induced by the network of neurons called central pattern generator has been reported to be modified by the information arising from the various oro-facial sensory receptors including muscle spindles of jaw closing muscles. The cell bodies of primary afferent neurons from these muscle spindles lie in mesencephalic trigeminal nucleus (MTN) in the brainstem. The aim of the study was to understand whether muscle spindles from jaw-closing muscles play any role in hard food chewing. Single neuronal discharge of muscle spindle afferents was recorded from the MTN simultaneous with jaw-movement and electromyograpic (EMG) activities of the left masseter (jaw-closing) muscle during chewing soft and hard foods (apple and pellet) in awake rabbits. Ten consecutive chewing cycles were taken for analysis. Discharge of nineteen muscle spindles from seven rabbits was successfully recorded. Muscle-spindle discharge was significantly higher during the closing phase of jaw-movement for the hard food chewing than for the soft food. The jaw-closing muscle EMG activity was significantly higher during hard food chewing compared to soft food. The spindle discharge was higher when the masseter muscle activity was greater for chewing hard food. Significant positive (r=0.822, p=<0.001) correlation was found between the difference of muscle activity between apple and pellet and the difference of spindle discharge between apple and pellet. Above findings suggest that the increase of spindle discharge during hard food chewing may play a role for facilitating jaw-closing muscle activities and thereby provides servo-assistance to jaw-closing muscles to compensate the hardness of food.

Modulation of Human Muscle Spindle Discharge by Arterial Pulsations - Functional Effects and Consequences

Arterial pulsations are known to modulate muscle spindle firing; however, the physiological significance of such synchronised modulation has not been investigated. Unitary recordings were made from 75 human muscle spindle afferents innervating the pretibial muscles. The modulation of muscle spindle discharge by arterial pulsations was evaluated by R-wave triggered averaging and power spectral analysis. We describe various effects arterial pulsations may have on muscle spindle afferent discharge. Afferents could be “driven” by arterial pulsations, e.g., showing no other spontaneous activity than spikes generated with cardiac rhythmicity. Among afferents showing ongoing discharge that was not primarily related to cardiac rhythmicity we illustrate several mechanisms by which individual spikes may become phase-locked. However, in the majority of afferents the discharge rate was modulated by the pulse wave without spikes being phase locked. Then we assessed whether these influences changed in two physiological conditions in which a sustained increase in muscle sympathetic nerve activity was observed without activation of fusimotor neurones: a maximal inspiratory breath-hold, which causes a fall in systolic pressure, and acute muscle pain, which causes an increase in systolic pressure. The majority of primary muscle spindle afferents displayed pulse-wave modulation, but neither apnoea nor pain had any significant effect on the strength of this modulation, suggesting that the physiological noise injected by the arterial pulsations is robust and relatively insensitive to fluctuations in blood pressure. Within the afferent population there was a similar number of muscle spindles that were inhibited and that were excited by the arterial pulse wave, indicating that after signal integration at the population level, arterial pulsations of opposite polarity would cancel each other out. We speculate that with close-to-threshold stimuli the arterial pulsations may serve as an endogenous noise source that may synchronise the sporadic discharge within the afferent population and thus facilitate the detection of weak stimuli.

An index of spindle efficacy obtained by measuring electroneurographic activity and passive tension in the rat soleus muscle

While muscle spindle afferent discharges are known to change with altered muscle use, the way in which the changes in spindle discharge are affected by modifications to the elastic properties of the muscle–tendon unit remains to analyze. This paper describes a methodology to define, in the rat, a spindle efficacy index. This index relates the spindle afferent discharges recorded from electroneurograms (ENG) due to muscle stretch to the passive elastic properties of the muscle–tendon unit quantified during the stretch imposed for the ENGs recordings. The stretches were applied to the rat soleus muscle after the Achilles tendon was severed. The spindle afferent discharges were characterized from the root mean square (RMS) values of electroneurograms (ENGs) recorded from the soleus nerve. The first step of the study was to validate the definition of dynamic and static indices (DI and SI) of spindle discharges from RMS-ENG as classically done when isolated afferents are studied. The slopes of the DI-stretch velocity or SI-stretch amplitude relationships gave the indices of spindle sensitivity under dynamic and static conditions, respectively. Incremental stiffness was calculated to describe the passive elastic properties during the dynamic and static phases of ramp and hold stretches applied at different amplitudes and velocities. The spindle efficacy index (SEI) is the ratio between the indices of spindle sensitivity and incremental stiffness values. Both spindle discharges and incremental stiffness increased with stretch amplitude under dynamic and static conditions. The corresponding SEI values were constant whatever the stretch amplitude. This result validates the relationship between spindle discharges and passive incremental stiffness. This method can be proposed to study, in the rat, the spindle function when the muscles are suspected to present changes in their neuromechanical properties.

Resting discharge of human muscle spindles is not modulated by increases in sympathetic drive.

There is evidence in experimental animals that, in addition to receiving fusimotor drive, muscle spindles are subject to modulation by the sympathetic nervous system. We examined the validity of this idea in human subjects by recording from muscle spindles in the relaxed ankle and toe extensor muscles during a strong and sustained physiological activation of muscle sympathetic outflow. Unitary recordings were made from 20 primary and 17 secondary muscle spindle afferents via a tungsten microelectrode inserted percutaneously into the peroneal nerve in 10 awake, healthy subjects seated with the legs supported in the extended position. ECG, blood pressure, respiration and calf circumference were also recorded. The majority of the muscle spindles were spontaneously active at rest; a background discharge was induced in four silent spindles by vibrating the tendon. A sustained increase in muscle vasoconstrictor activity, an increase in calf volume and a fall in pulse pressure were produced by subjects performing a 30-40 s maximal inspiratory breath-hold. Despite this strong increase in muscle sympathetic outflow no significant changes occurred in the discharge of either primary or secondary muscle spindle afferents, measured as a change in mean frequency and variability over sequential 5 s epochs and compared with the preceding period of rest. Strong chemoreceptor-driven sympathetic bursts during sustained expiratory breath-holds also failed to modulate the firing of 14 spindle endings. We conclude that a sustained, physiological increase in muscle sympathetic activity causes no detectable change in muscle spindle firing, lending no support to the concept that the sympathetic nervous system can influence the sensitivity of human muscle spindles directly.

Static fusimotor action during locomotion in the decerebrated cat revealed by cross-correlation of spindle afferent activity.

Cross-correlation of the discharges of muscle spindle afferents in ankle extensor and flexor muscles has been used to reveal the activity of static gamma (gammaS) motoneurones innervating chain intrafusal muscle fibres during locomotion. In the anaesthetised cat, the cross-correlation of spindle afferents, jointly innervated by a gammaS-efferent with chain fibre contacts, showed short duration synchrony (2-8 ms) when the efferent was stimulated repetitively. In pre-mammillary decerebrated cats, the cross-correlograms of discharges of some pairs of spindle afferents showed similar short duration peaks of synchronisation and these were interpreted as being due to a common gammaS drive to chain intrafusal muscle fibres. The incidence of synchrony was low, and was similar at rest (5 % of pairs) and during treadmill locomotion (7 % of pairs). Phase dependence of synchrony was evident during locomotion in the flexor muscle. The synchrony of muscle spindle afferent discharge is discussed in relation to estimates of the numbers of spindles contacted by individual gammaS-efferents.

The history of contraction of the wrist flexors can change cortical excitability.

Voluntary contractions induce thixotropic changes in intrafusal muscle fibres and hence, by induction or removal of "slack", the background discharge and sensitivity of spindle endings to stretch is altered. This study assessed whether such changes also altered the "excitability" of the motor cortex. Eleven subjects performed a series of voluntary conditioning contractions of the wrist flexors designed to remove slack in the intrafusal fibres (contract and test at intermediate length, termed "contract-test") or to introduce slack (contract at long length and test at intermediate length, termed "contract-long"). Surface electromyographic recordings were made from one wrist flexor, flexor carpi radialis. Subjects relaxed after each contraction, and 10 s later a test stimulus was applied to elicit a tendon tap response, H-reflex, or motor-evoked potential (MEP) to transcranial magnetic stimulation in the flexor carpi radialis. Each of the three test stimuli was applied during 15 consecutive pairs of contractions ("contract-long" and "contract-test"). Three subjects repeated the protocol using transmastoid electrical stimulation as the test stimulus to evoke a cervicomedullary motor-evoked potential (CMEP). For the group of subjects, after conditioning contractions designed to induce slack there was a significant reduction in the amplitude of the tendon reflex, no significant change in the H-reflex, and a small but significant reduction in the amplitude of the MEP. In one subject the CMEP was significantly reduced, while it was unchanged in two others. In the absence of corresponding changes in the H-reflex (or CMEP), changes in the size of the response to motor cortical stimulation suggest that the level of motor cortical "excitability" changes according to naturally induced variations in the discharge of muscle spindle afferents.

H-reflex modulation during passive lengthening and shortening of the human triceps surae.

1. The present study investigated the effects of lengthening and shortening actions on H-reflex amplitude. H-reflexes were evoked in the soleus (SOL) and medial gastrocnemius (MG) of human subjects during passive isometric, lengthening and shortening actions performed at angular velocities of 0, +/-2, +/-5 and +/-15 deg s(-1). 2. H-reflex amplitudes in both SOL and MG were significantly depressed during passive lengthening actions and facilitated during passive shortening actions, when compared with the isometric H-reflex amplitude. 3. Four experiments were performed in which the latencies from the onset of movement to delivery of the stimulus were altered. Passive H-reflex modulation during lengthening actions was found to begin at latencies of less than 60 ms suggesting that this inhibition was due to peripheral and/or spinal mechanisms. 4. It is postulated that the H-reflex modulation seen in the present study is related to the tonic discharge of muscle spindle afferents and the consequent effects of transmission within the Ia pathway. Inhibition of the H-reflex at less than 60 ms after the onset of muscle lengthening may be attributed to several mechanisms, which cannot be distinguished using the current protocol. These may include the inability to evoke volleys in Ia fibres that are refractory following muscle spindle discharge during rapid muscle lengthening, a reduced probability of transmitter release from the presynaptic terminal (homosynaptic post-activation depression) and presynaptic inhibition of Ia afferents from plantar flexor agonists. Short latency facilitation of the H-reflex may be attributed to temporal summation of excitatory postsynaptic potentials arising from muscle spindle afferents during rapid muscle lengthening. At longer latencies, presynaptic inhibition of Ia afferents cannot be excluded as a potential inhibitory mechanism.

Stimulation of chemosensitive afferents from multifidus muscle does not sensitize multifidus muscle spindles to vertebral loads in the lumbar spine of the cat.

Electrophysiologic recordings from muscle spindle afferents innervating the lumbar multifidus muscle of the cat while loading the L6 vertebra at its spinous process and while exposing the segmentally adjacent lumbar multifidus muscles to algesic and inflammatory mediators. The purpose of this study was to investigate a possible mechanism underlying muscle spasm and pain in the lumbar spine. The hypothesis was tested that stimulation of chemosensitive afferents with receptive endings in the paraspinal muscle increases the discharge of paraspinal muscle spindle afferents during loading of a lumbar vertebra. The presence of such a phenomenon would provide a mechanism by which pain or inflammation could alter segmental lumbar biomechanics and contribute to lumbar spine dysfunction. Muscle pain, tenderness, and altered muscle tone are often associated with musculoskeletal disorders. The literature suggests that stimulation of Group III and IV muscle afferents sensitive to algesic or inflammatory metabolites increases the stretch sensitivity of muscle spindles via a reflex pathway involving gamma-motoneurons. The reflex increase in muscle spindle activity, in turn, reflexly increases the excitability of alpha-motoneurons leading to enhanced muscle tone and the further accumulation of muscle metabolites and subsequent pain. Studies in the cervical spine support this hypothesis. It has not been investigated in the lumbar spine. Single unit activity from muscle spindles in the L6 multifidus muscle were recorded from the cut peripheral end of the L6 dorsal root in alpha-chloralose-anesthetized cats and in decerebrate unanesthetized cats. The L6 vertebra was loaded at its spinous process using a force-feedback motor. Ramp and hold loads were delivered at 25%, 50%, 75%, and 100% body weight. Chemosensitive afferents in the L5 and L7 multifidus muscle were stimulated by bathing (subfascial injection) or infiltrating (intramuscular injection) the L5 and L7 multifidus muscles with bradykinin or capsaicin. Loading the L6 vertebra stimulated muscle spindles in the L6 multifidus muscle. Neither the saline volume control nor bradykinin nor capsaicin injected subfascially or intramuscularly affected the response of L6 multifidus muscle spindles to ramp and hold vertebral loads in the alpha-chloralose-anesthetized cat. In addition, neither saline nor bradykinin nor capsaicin injected intramuscularly affected the activity of L6 multifidus muscle spindles to ramp and hold vertebral loads in the unanesthetized decerebrate cat. These results indicate that stimulation of small diameter muscle afferents in a deep muscle of the lumbar spine does not sensitize muscle spindles to vertebral loads. These data do not support the hypothesis that fusimotor reflexes evoked by chemosensitive muscle afferents contribute to muscle spasm or to changes in muscle tone in the lumbar spine. In addition, the present results do not provide evidence for the pain-spasm-pain cycle in the lumbar spine.

Time-dependent fusimotor effects on the discharge of cat primary muscle spindle afferents induced by a long-lasting succinylcholine infusion

The responses of 46 la afferents from the tibial anterior muscle of the cat to repetitive ramp-and-hold stretches were investigated under a succinylcholine (SCh) infusion of 120 μg · kg −1 · min −1 lasting 15 to 25 min. It was possible to distinguish four consecutive phases of the effect of the SCh on the responsiveness of the la afferents. The first three of these four phases have already been described. We analysed in more detail the changes from Phase III to the end of Phase IV. Static fusimotor effects were dominant in the discharge patterns obtained during Phase III; dynamic fusimotor effects prevail at the end of Phase IV. Our observations were quantified by comparing the mean values of initial activity, final static value, dynamic response and slow receptor adaptation read from the discharge patterns obtained during Phase III with the mean values of the same parameters obtained from discharge patterns from the end of Phase IV: the two mean values were significantly different for each of the four measurements. This change from Phase III to the end of Phase IV is highly specific for each spindle. To demonstrate this spindle specificity, discharge patterns were selected from among those produced by each la afferent in Phase III and at the end of Phase IV. Each of these discharge patterns was assigned to one of six categories. Category I displays purely dynamic fusimotor effects and Category VI purely static fusimotor effects. Categories II, IV and V display combinations of static and dynamic fusimotor effects with an increasing admixture of static fusimotor effects. The spindle-specific change from Phase III to the end of Phase IV is defined in terms of the specific degree of change from a higher-number to a lower-number category in the case of each of the 46 la afferents. In the discussion a combination of activity by the two nuclear bag fibres of a spindle is deduced from the specific discharge pattern of each category. The conclusion from these considerations is that results obtained from the administration of SCh have to be interpreted with great caution in making any statement about the existence of a dynamic bag 1 fibre in a spindle.

Inhibitory effect of sympathetic stimulation on activities of masseter muscle spindles and the jaw jerk reflex in rats.

1. To evaluate sympathetic effects on jaw muscles, the discharges of masseter muscle spindle afferents, jaw muscle electromyographic (EMG) activities and blood flow changes were compared in anaesthetized decerebrate rats before and during electrical stimulation of the cervical sympathetic trunk. 2. To eliminate the possibility of efferent control from the trigeminal motoneurones, muscle spindle activity was recorded from the cut peripheral end of the masseter nerve. The absence of a sympathetic component in the masseter nerve was confirmed by the horseradish peroxidase method. 3. Electrical stimulation of the sympathetic nerve at frequencies within the physiological range reduced muscle spindle afferent discharges evoked by passive jaw opening. 4. Sympathetic stimulation also reduced the EMG activity evoked by the jaw jerk reflex, which may reflect a sympathetic effect on spindle afferents. After cessation of stimulation, a transient increase in EMG activity was observed, which may be due to efferent supply from the trigeminal motoneurones. During rhythmical jaw movements, no sympathetic effect on EMG activity was detected. 5. The above sympathetic effect on muscle spindle afferents and EMG activity was independent of blood flow changes.

Dual response from human muscle spindles in fast voluntary movements

Single-unit impulses were recorded from the radial nerve of attending human subjects using the microneurography technique. The discharge of muscle spindle afferents from the extensor digitorum muscles was analysed while subjects performed fast lengthening and shortening voluntary movements as well as movements of moderate speed at a single metacarpophalangeal joint. Opposing or assisting loads of moderate size were added in some tests. Fast lengthening movements were, in practically all units, associated with acceleration of spindle discharge. However, the responses were modest and in many primary afferents it was of similar size as their response to small irregularities during slower movements. During shortening movements, most spindle afferents stopped firing altogether, whereas some afferents exhibited a distinct burst of impulses at the onset of active shortening followed by silence during the main part of the movement. This initial shortening responses was sometimes more prominent when the parent muscle worked against an opposing load. It was interpreted as a result of fusimotor drive associated with the building up of force in the contracting muscle. The initial shortening response from the contracting muscle and the stretch response from the antagonist constitute a dual signal, describing accurately the onset of joint movement as seen from the two muscles. It remains to be clarified which role this pattern of afferent responses may have in the design of the current motor output and in the capturing of nature and size of the external load.

Human muscle spindle response in a motor learning task.

1. Impulse discharge of single muscle spindle afferents from the finger extensor muscles was recorded in the radial nerve of conscious human subjects, during a motor learning task engaging the metacarpo-phalangeal joint of a single finger, using the microneurography technique. 2. Subjects were requested first to pay attention to a complex sequence of imposed single joint movements, and immediately afterwards to reproduce actively the same sequence. No external load was added to the finger and visual control was denied altogether so that subjects relied on mechanoreceptor input exclusively for the sampling and reproduction of movement. In addition, sequences of imposed movements were delivered while subjects were not attending in order to allow analysis of the attention effect. 3. The response of the individual unit was uniform in repeated tests. There were clear differences between spindle firing rate in imposed and actively reproduced movements with most units. However, the difference was complex during the individual sequence, in that firing rate was usually higher during periods of reproduced movements when the muscle was relatively short whereas it was identical when the muscle was relatively long. 4. The hypothesis that reproduction and verification of an imposed movement may be based on simple matching between identical spindle firing in imposed and active movements, was difficult to reject altogether because identical spindle input was present during considerable sections of the movement sequence. It may be speculated that agonists and antagonists cover different ranges of joint excursion, with identical spindle firing rates in imposed and reproduced movements. 5. Attention to imposed movements was associated with a minute and inconsistent increase of spindle firing rate in some afferents and then usually with a slight increase of EMG activity of the parent muscle as well. 6. It was concluded that focusing attention on the kinaesthetic input during imposed movement was not associated with a consistent increase of fusimotor drive.

Stereoencephalotomy and control of skeletal muscle tone.

Following therapeutic stereotactic lesions in the ventrolateral subthalamus and adjacent nuclei there are two phenomena concerning muscle tone: decreased muscle stiffness and failure in load compensation. In order to clarify whether hypotonia is due to decreased reflex activity and/or reduced nonreflex muscle stiffness, torque-induced stretch responses in the forearm flexor muscles and muscle spindle afferent discharge were investigated. In hypotonia following these lesions, the immediate compensation of abrupt external perturbations was diminished prior to reflex onset. A special feedback system is presented which originates in skeletal muscles and which continuously controls the muscle stiffness during movements. This afferent fiber system probably has a greater representation at the thalamic level as compared to the peripheral nerve. It is assumed that the decrease in muscle stiffness as well as the failure in load compensation are due to diminished static gamma-drive. This lack in somatosensory feedback can be compensated voluntarily by changing the mode of innervation.

Reflex influences on muscle spindle activity in relaxed human leg muscles.

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

Effects of tizanidine, a centrally acting muscle relaxant, on motor systems

1. 1. Effects of tizanidine were studied with special reference to the effect on motor systems. 2. 2. The drug effectively reduced the intercollicular decerebrate rigidity and γ-activity indirectly recorded from muscle spindle afferent discharges without showing the direct inhibitory effect on muscle spindles in rats. 3. 3. The drug dose-dependently inhibited the phasic responses of α-rigidity in anemic decerebrate rats without showing marked inhibition of the tonic response. 4. 4. Tizanidine effectively depressed the crossed extensor reflex in chicks and depressed mono- and polysynaptic reflex potentials in rats; dorsal root reflex was increased transiently. 5. 5. Tizanidine had no effect on the neuromuscular junction in rats and [ 3H]diazepam binding in rat brain membrane. 6. 6. It is suggested that the depression by tizanidine of γ-system and spinal reflexes contribute to muscle relaxation and anti-spastic effects and that mechanisms of action are different from those of other centrally acting muscle relaxants such as mephenesin and benzodiazepines.

Tendon organ firing during active muscle lengthening in awake, normally behaving cats.

Recordings were obtained of the discharge of single tendon organ (Ib) and muscle spindle (Ia) afferents of the ankle extensor muscles during movement in normal cats. During very slow, smooth increases and decreases in muscle force, Ib afferents showed from one to five stepwise changes in firing rate, attributable to the recruitment of motor units inserting into the receptor capsule. These 'recruitment steps' in Ib firing rate became smoothed and tended to merge during faster variations in muscle force, and were rarely discernible in normal movements such as slow stepping. Rapid imposed stretches resulted in Ib firing patterns which fitted well a dynamic function of whole muscle force. Comparisons were made between the responses of Ib and Ia afferents during rapid, imposed muscle stretch. The segmentation of discharge typical of Ia afferents was not present in Ib afferents, despite segmentation of the e.m.g. of the receptor-bearing muscles. This would imply that Ib afferents exert a rapidly fluctuating reflex action against a relatively steady background of Ib input. Ankle extensor Ib firing during stepping was characterized by feeble firing during the swing phase and substantial, smoothly modulated firing during the stance phase. Taken together with previous chronic recordings, the data support the view that the ensemble of Ib afferents from a muscle signals a dynamic, non-linear function of whole muscle force over a wide range of normal movement.

Rehabilitation following brain damage: some neurophysiological mechanisms. Physiological correlates of clinically observed changes in posture and tone following lesions of the central nervous system.

Extensive investigation of the role of the fusimotor system in the production of hypotonic and hypertonic disorders of posture and tone has been undertaken in humans and experimental animals. The data from human studies have usually been from indirect assessment of the fusimotor system, and results are often contradictory. Results are now available from animal studies utilizing direct recording of muscle spindle afferent discharge in a number of models of human disorder. Conditions resulting in hypotonia, e.g. cerebellar ablations, medullary pyramidotomy, VL nucleus, thalamotomy, acute spinal cord transection, and acute motor cortex ablation uniformly result in a depression of muscle spindle primary afferent discharge. Conditions resulting in hypertonia, e.g. chronic spinal cord transection and chronic motor cortex ablation, fail to show heightened muscle spindle afferent discharge, however. Rather the spindle afferent discharge returns to control levels in the models. Recovery from the hypotonic to the hypertonic state is, however, associated with significant recovery of spindle afferent function.

Effect of catechol on the discharge of muscle spindle afferents from the hind limb of the rat

Previous work had shown that some of the effects of catechol could be via the fusimotor system. In order to determine the extent of fusimotor involvement, recordings have been made from muscle spindle afferents in split dorsal root filaments of anaesthetised rats. Catechol failed to excite de-efferented muscle spindles therefore eliminating many possible non-fusimotor effects. Over 80% of spindle afferents with intact efferents showed increased discharge frequency 1 min after injection, this increase often following a biphasic pattern with a pronounced pre-myoclonic burst and decline followed by a more sustained period of activity during the myoclonic phase. Analysis of spontaneous twitches or twitches evoked by ipsilateral auditory stimulation showed in addition a phasic increase in discharge suggesting α-γ co-activation. Both primary and secondary afferents from many muscle groups around ankle and toes had their discharge frequencies elevated. Elevation of discharge frequencies of secondaries implies increased γ-s activity confirmed by a decrease in dynamic index. Both γ-d and γ-s involvement in catechol action on primaries is suggested by dynamic index measurements. Perhaps a more continuous form of testing such as sinusoidal stretches would reveal any rapid switching between activities in the two systems.

Rat isolated phrenic nerve-diaphragm preparation for pharmacological study of muscle spindle afferent activity: effect of oxotremorine.

1. Muscle spindle afferent discharges exhibiting an approximately linear length-frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve-diaphragm preparation of the rat. 2. Muscle spindle afferent discharges could be identified by their characteristic "spindle pause" during muscle contraction and by their response to succinylcholine. 3. Cholinergic influence on spontaneous and stretch-induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)-Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles. 4. Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium-3 and (+)-tubocurarine failed to affect the rate of spontaneous and stretch-induced spindle discharges. 5. Oxotremorine markedly increased the rate of spontaneous and stretch-induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium-3 and (+)-tubocurarine. 6. These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents and hyperactive in Parkinsonian patients.

Mode of action of L-dopa on .GAMMA.-motor system in the rat.

The effect of L-dopa on γ-motor system, especially on static γ-activity induced by pinna pinching, was investigated in the anesthetized rats. γ-Activity was detected indirectly as the change in the rate of muscle spindle afferent discharges. L-Dopa (25-100 mg/kg, i. v.) caused a dose-dependent inhibition in static γ-activity. The effect of L-dopa was reduced significantly by the pretreatment with α-methyl-dopa (400 mg/kg, i. p.). On the other hand, the pretreatment with disulfiram (400mmg/kg, i. p.) augmented the inhibitory effect of L-dopa. Phenoxybenzamine hydrochloride (2.5 mg/kg, i.v.) augmented the inhibitory effect of L-dopa, whereas haloperidol (0.025 mg/kg, i.v.) had no influence on the effect of the drug. Amphetamine sulfate (2.5 mg/kg, i.v.) and amantadine hydrochloride (10 mg/kg, i.v.) facilitated static γ-activity, and effects of these drugs were considerably reduced by the pretreatment with disulfiram and inhibited by phenoxybenzamine hydrochloride (10 mg/kg, i. v.). These results suggest that L-dopa exerts its inhibitory effect after being metabolized to dopamine, and that amphetamine and amantadine exhibit their facilitatory actions on the static γ-activity through the noradrenergic pathways.