A numerical simulation of muscle spindle ensemble encoding during planar movement of the human arm

We address the issue of what proprioceptive information, regarding movement of the human arm, may be provided to the central nervous system by proprioceptors located within muscles of this limb. To accomplish this we developed a numerical simulation which could provide estimates of the length regimes experienced by a set of model receptors located within some of the principal muscles of the human arm during planar movement of this limb. These receptors were assumed to have characteristics analogous to those associated with a simple model of muscle spindle signalling of movement. To this end each spindle had proprioceptive ‘channels’ associated with it. These corresponded to primary and secondary spindle afferent fibers which could provide independent afferent output regarding the parent muscle the spindle monitored. The angles of the shoulder and elbow joints attained by subjects performing a task requiring movement of the right arm in a horizontal plane to a static visual target were recorded. For this angular data the lengths and rates of change of lengths experienced by muscle fascicles, and hence the model spindles, during movement were calculated by means of the numerical simulation. The discharge rates of the simulated spindles during the movement were calculated to derive a measure of the depth of modulation, induced by the movement, for each spindle. These values were then summed for all spindles to provide a first-order approximation of spindle ensemble coding of the movement. Significant correlations (0.0001, Spearman's rank order) were found between the resulting ensemble encodings and, in order of significance, the angular velocity of the shoulder joint (), the tangential velocity of the hand (), and the angular velocity of the elbow joint (). Correlations between the angular positions of the shoulder () and elbow () were lower. These findings indicate that the ensemble profiles of the simulated muscle spindles, encode information regarding kinematic parameters of movements related to both intrinsic and extrinsic coordinate systems. This suggests that motor structures capable of deriving such an ensemble encoding would be in a position to perform the sensory-motor transformations between intrinsic and extrinsic frames of reference necessary for controlling movements planned in extrinsic coordinates. Received: 12 August 1994 / Accepted in revised form: 17 June 1996     

Somatosensory unit input to the spinal cord during normal walking

Chronic recording techniques in freely walking cats have been used to sample unitary activity from most large myelinated afferent classes. Cutaneous mechanoreceptors are highly sensitive and generate regular activity patterns predictable from their modalities. Knee joint afferents can fire briskly midrange locomotory movements but appear to be influenced by factors other than joint angle. Golgi tendon organs generate activity consistent with sensitivity to active muscle tension. Muscle spindle afferents do not appear to conform to any single functional pattern for all muscles. It is suggested that degree and rate of stretch are sensed by spindles (possibly under dynamic fusimotor bias) in extensor muscles which normally undergo isometric or lengthening contractions whereas rapidly modulated static fusimotor activity is employed to preserve spindle activity during the rapidly shortening contractions of flexor muscles. Both patterns may be represented in different spindles of bifunctional, biarticular muscles such as rectus femoris and sartorius.     

Fusimotor reflex profiles of individual triceps surae primary muscle spindle afferents assessed with multi-afferent recording technique.

The experiments were performed on 21 cats anaesthetized with alpha-chloralose. The aim of the study was to investigate sets of simultaneously recorded spindle afferents (2-4 in each set) from the triceps surae muscle (GS) with respect to the pattern of fusimotor reflex effects evoked by different types of ipsi- and contralateral reflex stimulation. The afferents' responses to sinusoidal stretching of the GS muscle were determined and the fusimotor reflex effects were assessed by comparing the afferent responses (i.e. the mean rate of firing and the depth of modulation) elicited during reflex stimulation with those evoked in absence of any reflex stimulus. Natural of electrical activations of ipsi- and contralateral muscle, skin and joint receptor afferents were used as reflex stimuli. The spindle afferents were influenced by several modalities and from wide areas, with a majority responding to both ipsi- and contralateral stimuli. A particular reflex stimulus often caused different effects on different afferents, and the various reflex stimuli seldom gave similar effects on a particular afferent. Multivariate analysis revealed that the variation in response profiles among simultaneously recorded afferents were as great as between afferents recorded on different occasions. This suggests that the individualized response prifiles, observed in earlier investigations, represent a very diversified reflex control of the spindle primary afferents, and are not a reflection of changes in the setting of the spinal interneuronal network, occurring during the time interval between the recordings of different units. Also, there was no relation between the conduction velocity of the afferents and the reflex profiles of the afferents, but non-linear relations were found between effects elicited by different types of stimuli. Indications were also found that it may be possible to separate the population of GS muscle spindles into subgroups, according to the fusimotor effects exhibited by activation of various categories of ipsi- and contralateral receptor afferents. It is concluded that one possible way of making the very complex reflex system controlling the muscle spindles intelligible may be a combination of multiple simultaneous recordings of spindle afferents and multivariate analysis.     

大鼠单一肌梭的电生理特征

本研究旨在观察大鼠单一肌梭的电生理特征.从大鼠比目鱼肌中分离单一肌梭,用空气隔绝法观察大鼠单一肌梭感觉末梢在不同液体环境中的放电活动.结果显示:在基础生理盐水溶液中,大鼠单一肌梭的自发放电频率很低,平均(51.78±25.63) impulse/1000s(n=13);在加有适量氨基酸的生理盐水溶液中,其自发放电频率明...     

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.     

Muscle-derived neurotrophin-3 reduces injury-induced proprioceptive degeneration in neonatal mice.

During perinatal development, proprioceptive muscle afferents are quite sensitive to nerve injury. Here, we have used transgenic mice that overexpress neurotrophin-3 (NT-3) in skeletal muscle (myo/NT-3 mice) to explore whether NT-3 plays a neuroprotective role for perinatal muscle afferents following nerve injury. Measurements of NT-3 mRNA using RT-PCR revealed that levels of endogenous NT-3 mRNA in wild-type muscles remained constant during the first postnatal week following nerve crush or nerve section on postnatal day (PN) 1. In comparison, myo/NT-3 mice had significantly elevated levels of NT-3 mRNA that were maintained or increased following injury. To assess whether muscle-derived NT-3 could prevent injury-induced neuronal death, neuron survival in the DRG was analyzed in mice 5 days after sciatic nerve crush on PN3. Retrograde prelabeling of muscle afferents and parvalbumin immunocytochemistry both revealed that overexpression of NT-3 in muscle significantly reduced neuronal loss following injury. Similar neuroprotective effects of NT-3 were observed in wild-type mice injected with exogenous NT-3 in the gastrocnemius muscles. To test whether NT-3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1. No spindles were present in either wildtype or myo/NT-3 muscles after nerve section, demonstrating that NT-3 overexpression cannot maintain spindles following complete denervation. Moreover, NT-3 overexpression could not prevent moderate spindle loss in muscle and did not stimulate new spindle formation following nerve crush. Our results demonstrate that in addition to its early actions on sensory neuron generation and naturally occurring cell death, NT-3 has important neuroprotective effects on muscle afferents during postnatal development.     

Spinal and supraspinal effects of activity in ligament afferents.

In this paper available knowledge on effects from joint and ligament afferents on spinal neurones and pathways are briefly reviewed, and possible functional implications discussed. Ligament afferents may contribute to joint stability, muscle coordination and proprioception through direct polysynaptic reflex effects onto ascending pathways and skeletomotoneurones, and/or indirectly via reflex actions on the gamma-muscle spindle system. Theoretical and experimental evidence indicate that ligament afferents, together with afferents from other joint structures, muscles and the skin, provide the CNS with information on movements and posture through ensemble coding mechanisms, rather than via modality specific private pathways. The existence and functional relevance of ligamentomuscular protective reflexes, that are triggered when the ligament is threatened by potentially harmful loads, has been seriously questioned. It seems more likely that peripheral sensory inputs from ligament afferents participate in a continuous control of the muscle activity through feedforward, or preprogramming, mechanisms. In line with these ideas it has been suggested that ligament mechanoreceptors have an important role in muscle coordination and in the reflex regulation of the functional joint stability, by contributing to the preprogramming of the muscle stiffness through reflex modulation of the gamma-muscle spindle system.     

Proprioception during voluntary movement

In the last decade, a number of laboratories have accumulated data on the firing of single afferent fibres from muscle and skin during movement in awake cats, monkeys and human subjects. While there is general agreement on the firing behaviour of skin afferents and tendon organ (Ib) afferents during movement, there remains a significant divergence of opinion regarding the way in which the response of muscle spindle afferents (Ia and II) to length changes is modified by fusimotor action (e.g., alpha-gamma linkage versus "fusimotor set"). The controversies surrounding the fusimotor system have tended to overshadow the emergence of several important characteristics of proprioceptive behaviour, corroborated in separate laboratories. (i) Mean Ia firing rates during active movements are nearly always higher than at rest. Thus, activation of the fusimotor system is reserved for the control of, or preparation for, movement. In animals, there is now strong evidence that there is usually a tonic component of fusimotor action during rhythmical movements. (ii) During fast, unloaded movements (peak muscle speeds, 0.2 resting lengths/s or more), the firing of both Ia and II afferents usually increases during lengthening and decreases during shortening. Ib afferents fire during even the most rapid active shortening of their parent muscles. (iii) During powerful shortening contractions performed against significant loads, Ia firing is often appreciable, suggesting that there is at least some underlying alpha-gamma coactivation. (iv) During fast imposed muscle stretches, Ia afferents respond with segmented bursts of firing (threshold speed for segmentation, 0.5-1.0 resting length/s). Ib afferents show far less segmentation of discharge under similar circumstances.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heterogeneity of spindle units in the cat tenuissimus muscle

Three tandem spindles and their nerve supplies, reconstructed by light microscopy of serial transverse sections of the cat tenuissimus muscle, were compared to single spindle units. Each tandem spindle consisted of one large unit containing a dynamic bag1, a static bag2, and several static chain fibers (b1b2c unit) linked by the bag2 fiber to a small unit containing only a bag2 and chain fibers (b2c unit). Most features of primary afferents, secondary afferents, and motor neurons were qualitatively and quantitatively similar in both single and tandem b1b2c units. However, b1b2c units of tandem spindles had a lower density of skeletofusimotor innervation than did single b1b2c spindles. The b2c spindle units differed greatly from single or tandem b1b2c units. The b2c spindle units had fewer intrafusal fibers and incoming axons than either the tandem or single b1b2c units. The motor innervation of b2c units was typified by nonselective gamma axons that coinnervated both bag2 and chain fibers, in contrast to the regular occurrence of both selective and nonselective motor axons in b1b2c spindle units. The afferent located at the equator of b2c units differed in size, branching pattern, and intrafusal distribution of its ending from both the primary and secondary sensory axons of b1b2c units and, therefore, might represent a third category of spindle afferent. Thus, cat tenuissimus muscles contain three types of spindle units that differ in the number and organization of muscular and neural elements. These differences in structure and neural organization among tenuissimus spindle units may be a source for generation of different sensory signals in response to common mechanical or fusimotor stimuli.     

Re-examination of a linear systems approach to the behavior of mammalian muscle spindles

A model consisting of the parallel arrangement of one position-dependent and three first order velocity-dependent components is proposed in order to describe the behavior of muscle spindles. The responses of spindle receptors to ramp stretches have previously been characterized by fractional power functions; the aim of this study is to generate these functions on the basis of a simple additive linear model. A procedure is described which yields model parameters from responses to ramp and triangular displacements. Tests of the model are performed by comparing its predictions with experimental data from muscle spindles in cat and rat.     

Muscle‐derived neurotrophin‐3 reduces injury‐induced proprioceptive degeneration in neonatal mice

During perinatal development, proprioceptive muscle afferents are quite sensitive to nerve injury. Here, we have used transgenic mice that overexpress neurotrophin‐3 (NT‐3) in skeletal muscle (myo/NT‐3 mice) to explore whether NT‐3 plays a neuroprotective role for perinatal muscle afferents following nerve injury. Measurements of NT‐3 mRNA using RT‐PCR revealed that levels of endogenous NT‐3 mRNA in wild‐type muscles remained constant during the first postnatal week following nerve crush or nerve section on postnatal day (PN) 1. In comparison, myo/NT‐3 mice had significantly elevated levels of NT‐3 mRNA that were maintained or increased following injury. To assess whether muscle‐derived NT‐3 could prevent injury‐induced neuronal death, neuron survival in the DRG was analyzed in mice 5 days after sciatic nerve crush on PN3. Retrograde prelabeling of muscle afferents and parvalbumin immunocytochemistry both revealed that overexpression of NT‐3 in muscle significantly reduced neuronal loss following injury. Similar neuroprotective effects of NT‐3 were observed in wild‐type mice injected with exogenous NT‐3 in the gastrocnemius muscles. To test whether NT‐3 could prevent muscle spindle degeneration, spindle number and morphology were assessed 3 weeks after sciatic nerve crush or section on PN1. No spindles were present in either wildtype or myo/NT‐3 muscles after nerve section, demonstrating that NT‐3 overexpression cannot maintain spindles following complete denervation. Moreover, NT‐3 overexpression could not prevent moderate spindle loss in muscle and did not stimulate new spindle formation following nerve crush. Our results demonstrate that in addition to its early actions on sensory neuron generation and naturally occurring cell death, NT‐3 has important neuroprotective effects on muscle afferents during postnatal development. © 2002 Wiley Periodicals, Inc. J Neurobiol 50: 198–208, 2002; DOI 10.1002/neu.10024     

Model-based prediction of fusimotor activity and its effect on muscle spindle activity during voluntary wrist movements

Muscle spindles provide critical information about movement position and velocity. They have been shown to act as stretch receptors in passive muscle, however, during active movements their behavior is less clear. In particular, spindle responses have been shown to be out-of-phase or phase advanced with respect to their expected muscle length-sensitivity. Whether this apparent discrepancy of spindle responses between passive and active movements is due to fusimotor (γ-drive) remains unresolved, since the activity of fusimotor neurons during voluntary non-locomotor movements are largely unknown. We developed a computational model to predict fusimotor activity and to investigate whether fusimotor activity could explain the empirically observed phase advance of spindle responses. The model links a biomechanical wrist model to length- and γ-drive-dependent transfer functions of type Ia and type II muscle spindle activity. Our simulations of two wrist-movement tasks suggest that (i) experimentally observed type Ia and type II activity profiles can to a large part be explained by appropriate, i.e. strongly modulated and task-dependent, γ-drive. That (ii) the empirically observed phase advance of type Ia or of type II profiles during active movement can be similarly explained by appropriate γ-drive. In summary, the simulation predicts that a highly task-modulated activation of the γ-system is instrumental in producing a large part of the empirically observed muscle spindle activity for voluntary wrist movements.     

Slow-tonic MHC expression in paralyzed hindlimbs of fetal rats.

Whether nerve activity and active contraction of myotubes are essential for the assembly and initial differentiation of muscle spindles was investigated by paralyzing fetal rats with tetrodotoxin (TTX) from embryonic day 16 (E16) to E21, prior to and during the period when spindles typically form. TTX-treated soleus muscles were examined by light and electron microscopy for the presence of spindles and expression of myosin heavy chain (MHC) isoforms by the intrafusal fibers. Treatment with TTX did not inhibit the formation of a spindle capsule or the expression of a slow-tonic MHC isoform characteristic of intrafusal fibers, but did retard development of spindles. Spindles of TTX-treated E21 muscles usually consisted of one intrafusal fiber (bag2) only rather than two fibers (bag1 and bag2) typically present in untreated (control) E21 spindles. Intrafusal fibers of TTX-treated spindles also had only one sensory region supplied by multiple afferents, and were devoid of motor innervation. These features are characteristic of spindles in normal E18-E19 muscles. Thus, nerve and/or muscle activity is not essential for the assembly of muscle spindles, formation of a spindle capsule, and transformation of undifferentiated myotubes into the intrafusal fibers containing spindle-specific myosin isoforms. However, activity may promote the maturation of intrafusal bundles, as well as the maturation of afferent and efferent nerve supplies to intrafusal fibers.     

Separation and estimation of muscle spindle and tension receptor populations by vibration of the biceps muscle in the frog

Frog spinal cord reflex behaviors have been used to test the idea of spinal primitives. We have suggested a significant role for proprioception in regulation of primitives. However the in vivo behavior of spindle and golgi tendon receptors in frogs in response to vibration are not well described and the proportions of these proprioceptors are not established. In this study, we examine the selectivity of muscle vibration in the spinal frog. The aim of the study was (1) to examine how hindlimb muscle spindles and GTO receptors are activated by muscle vibration and (2) to estimate the relative numbers of GTO receptors and spindle afferents in a selected muscle, for comparison with the mammal. Single muscle afferents from the biceps muscle were identified in the dorsal roots. These were tested in response to biceps vibration, intramuscular stimulation and biceps nerve stimulation. Biceps units were categorized into two types: First, spindle afferents which had a high conduction velocity (approximately 20-30 m/s), responded reliably (were entrained 1:1) to muscle vibration, and exhibited distinct pauses to shortening muscle contractions. Second, golgi tendon organ afferents, which had a lower conduction velocity (approximately 10-20 m/s), responded less reliably to muscle vibration at physiologic muscle lengths, but responded more reliably at extended lengths or with background muscle contraction, and exhibited distinct bursts to shortening muscle contractions. Vibration responses of these units were tested with and without muscle curarization. Ensemble (suction electrode) recordings from the dorsal roots were used to provide rough estimates of the proportions of the two muscle afferent types.     

Role of nerve and muscle factors in the development of rat muscle spindles

The soleus muscles of fetal rats were examined by electron microscopy to determine whether the early differentiation of muscle spindles is dependent upon sensory innervation, motor innervation, or both. Simple unencapsulated afferent-muscle contacts were observed on the primary myotubes at 17 and 18 days of gestation. Spindles, encapsulations of muscle fibers innervated by afferents, could be recognized early on day 18 of gestation. The full complement of spindles in the soleus muscle was present at day 19, in the region of the neuromuscular hilum. More afferents innervated spindles at days 18 and 19 of gestation than at subsequent developmental stages, or in adult rats; hence, competition for available myotubes may exist among afferents early in development. Some of the myotubes that gave rise to the first intrafusal (bag2) fiber had been innervated by skeletomotor (alpha) axons prior to their incorporation into spindles. However, encapsulated intrafusal fibers received no motor innervation until fusimotor (gamma) axons innervated spindles 3 days after the arrival of afferents and formation of spindles, at day 20. The second (bag1) intrafusal fiber was already formed when gamma axons arrived. Thus, the assembly of bag1 and bag2 intrafusal fibers occurs in the presence of sensory but not gamma motor innervation. However, transient innervation of future bag2 fibers by alpha axons suggests that both sensory and alpha motor neurons may influence the initial stages of bag2 fiber assembly. The confinement of nascent spindles to a localized region of the developing muscle and the limited number of spindles in developing muscles in spite of an abundance of afferents raise the possibility that afferents interact with a special population of undifferentiated myotubes to form intrafusal fibers.     

Localization of neurons innervating masticatory muscle spindle and periodontal receptors in the mesencephalic trigeminal nucleus and their reflex actions

The mesencephalic trigeminal nucleus was studied in anaesthetized and curarized rabbits by recording the unitary activity through extracellular microelectrodes and identifying the constituent cell types. Two types of units were found, namely primary afferents supplying jaw raising muscle spindles and periodontal or gingival mechanoreceptors. These two groups of neurons exhibited a rostrocaudal somatotopy: the former occupied the entire rostral portion of the nucleus (A7-P2.3; trochlear decussation being taken as an arbitrary 0 level), the latter was located caudally (P3-P4.5) while the somata of both types of afferent fibres were present between P2.2 and P3. No evidence was found for representation of both tendon organs of jaw muscles and joint receptors. Among the units innervating muscle spindles, secondary afferents were largely more numerous than the primary ones. Among periodontal and gingival mechanoreceptor afferents, incisors were the most widely represented, followed by interalveolar gingiva and molars; the axonal conduction velocity ranged between 9 and 40 m/sec and between 8 and 16 m/sec for ipsilaterally and contralaterally projecting neurons, respectively. The motor responses obtained by electrical stimulation of discrete areas of the MTN confirmed the presence of a high degree of segregation between the two different populations of neurons. In fact, jaw raising movements are obtained when stimulating the area within A7 and P2 containing the somata of spindle afferent neurons, while only jaw opening movements are elicited by stimulation of the caudal levels of the nucleus. These data also show that the periodontal neurons whose somata are located in the MTN participate in the jaw opening reflex, just as the more numerous periodontal mechanoreceptors whose somata are located in the Gasser ganglion. Soma-somatic and soma-axon hillock gap junctions were found among the neurons of the MTN, particularly in the caudal third of the nucleus.     

Innervation of regenerated spindles in muscle grafts of the rat

Features of the nerve supply and the encapsulated fibers of muscle spindles were assessed in grafted and normal extensor digitorum longus (EDL) muscles of rats by analysis of serial 10-microns frozen transverse sections stained for enzymes which delineated motor and sensory endings, oxidative capacity and muscle fiber type. The number of fibers was significantly more variable, and branched fibers were more frequently observed in regenerated spindles than in control spindles. Forty-eight percent of regenerated spindles received sensory innervation. Spindles reinnervated by afferents had a larger periaxial space than did spindles which were not reinnervated by afferents. Regenerated fibers innervated by afferents had small cross-sectional areas, equatorial regions with myofibrils restricted to the periphery of fibers, unpredictable patterns of nonuniform and nonreversible staining along the length of the fiber for 'myofibrillar' adenosine triphosphatase (mATPase) after acid and alkaline preincubation. In contrast, regenerated fibers devoid of sensory innervation resembled extrafusal fibers in that they usually exhibited myofibrils throughout the length of the fiber, no central aggregations of myonuclei, uniform staining for mATPase and a reversal of staining for mATPase after preincubation in an acid or alkaline medium. Approximately thirty percent of encapsulated fibers devoid of sensory innervation stained analogous to a type I extrafusal fiber, a pattern of staining never observed in intrafusal fibers of normal spindles. Groups of encapsulated fibers all exhibiting this pattern of staining reflect that either these fibers may have been innervated by collaterals of skeletomotor axons that originally innervated type I extrafusal fibers or that fibers innervated by only fusimotor neurons express patterns of staining for mATPase similar to extrafusal fibers in the absence of sensory innervation. Sensory innervation may also influence the reestablishment of multiple sites of motor endings on regenerated intrafusal fibers. Those regenerated fibers innervated by afferents had more motor endings than did regenerated fibers devoid of sensory innervation. Differences in size, morphology, and patterns of staining for mATPase and numbers of motor endings between fibers innervated by afferents and fibers devoid of sensory innervation reflect that afferents can influence the differentiation of muscle cells and the reestablishment of motor innervation other than during the late prenatal/early postnatal period when muscle spindles form and differentiate in rats.     

Fusimotor reflexes influencing secondary muscle spindle afferents from flexor and extensor muscles in the hind limb of the cat.

The purpose of this study was to investigate secondary muscle spindle afferents from the triceps-plantaris (GS) and posterior biceps and semitendinosus (PBSt) muscles with respect to their fusimotor reflex control from different types of peripheral nerves and receptors. The activity of single secondary muscle spindle afferents was recorded from dissected and cut dorsal root filaments in alpha-chloralose anaesthetized cats. Both single spindle afferents and sets of simultaneously recorded units (2-3) were investigated. The modulation and mean rate of firing of the afferent response to sinusoidal stretching of the GS and PBSts muscle were determined. Control measurements were performed in the absence of any reflex stimulation, while test measurements were made during reflex stimulation. The reflex stimuli consisted of manually performed movements of the contralateral hind limb, muscle stretches, ligament tractions and electrical stimulations of cutaneous afferents. Altogether 21 secondary spindle afferents were investigated and 20 different reflex stimuli were employed. The general responsiveness (i.e. number of significant reflex effects/number of control-test series) was 52.4%, but a considerable variation between different stimuli was found, with the highest (89.9%) for contralateral whole limb extension and the lowest (25.0%) for stretch of the contralateral GS muscle. The size of the response to a given stimulus varied considerably between different afferents, and, in the same afferent, different reflex stimuli produced effects of varying size. Most responses were characterized by an increase in mean rate of discharge combined with a decrease in modulation, indicative of static fusimotor drive (Cussons et al., 1977). Since the secondary muscle spindle afferents are part of a positive feedback loop, projecting back to both static and dynamic fusimotor neurones (Appelberg Et al., 1892 a, 1983 b; Appelberg et al., 1986), it is suggested that the activity in the loop may work like an amplified which, during some circumstances, enhance the effect of other reflex inputs to the system (Johansson et al., 1991 b).     

Slow-tonic MHC expression in paralyzed hindlimbs of fetal rats

Summary Whether nerve activity and active contraction of myotubes are essential for the assembly and initial differentiation of muscle spindles was investigated by paralyzing fetal rats with tetrodotoxin (TTX) from embryonic day 16 (E16) to E21, prior to and during the period when spindles typically form. TTX-treated soleus muscles were examined by light and electron microscopy for the presence of spindles and expression of myosin heavy chain (MHC) isoforms by the intrafusal fibers. Treatment with TTX did not inhibit the formation of a spindle capsule or the expression of a slow-tonic MHC isoform characteristic of intrafusal fibers, but did retard development of spindles. Spindles of TTX-treated E21 muscles usually consisted of one intrafusal fiber (bag₂) only rather than two fibers (bag₁ and bag₂) typically present in untreated (control) E21 spindles. Intrafusal fibers of TTX-treated spindles also had only one sensory region supplied by multiple afferents, and were devoid of motor innervation. These features are characteristic of spindles in normal E18–E19 muscles. Thus, nerve and/or muscle activity is not essential for the assembly of muscle spindles, formation of a spindle capsule, and transformation of undifferentiated myotubes into the intrafusal fibers containing spindle-specific myosin isoforms. However, activity may promote the maturation of intrafusal bundles, as well as the maturation of afferent and efferent nerve supplies to intrafusal fibers.     

Neural organization of spindles in three hindlimb muscles of the rat.

The neuroanatomical organization of the dynamic (bag1) and static (bag2 and chain) intrafusal systems was compared by light and electron microscopy of serial sections among 71 poles of muscle spindle in soleus (SOL), extensor digitorum longus (EDL), and lumbrical (LUM) muscles in the rat. Eighty-four percent of 195 fusimotor (gamma) axons to the spindles innervated either the dynamic bag1 fiber or the static bag2 and/or chain fibers. Sixteen percent of the gamma axons coinnervated the dynamic and static intrafusal fibers. Some of these nonselective axons were branches of effernts that also gave rise to axons selective to either the dynamic or static types of intrafusal fibers in one or more spindles. Thus activation of individual stem gamma efferents might not have a purely dynamic or purely static effect on the integrated afferent outflow from spindles of a hindlimb muscles in the rat. In addition, primary afferents in all muscles had terminations that cross-innervated the dynamic bag1 and static bag1 and/or chain intrafusal fibers in individual spindles, an arrangement that may enhance the mixed dynamic/static behavior of afferents when different intrafusal fibers are activated concurrent. Spindles of the slow SOL and fast EDL muscles had similar features, whereas differences were observed in the organization of the proximal (SOL and EDL) and distal (LUM) muscles. Spindles in LUM muscles had fewer static intrafusal fibers, a higher ratio of dynamic to static gamma axons, and a higher incidence of skeletofusimotor (beta) innervation to intrafusal fibers than spindles in the SOL or EDL muscles. Thus, the relative contribution of dynamic and static systems to muscle afferent outflow may differ among spindles located in different segments of the rat hindlimb. However, the dynamic and static intrafusal systems of spindle were less sharply demarcated in each of the three hindlimb rat muscles than in the cat tenuissimus muscle.