[Research progress on muscle spindle morphology].

Muscle spindle is the key proprioceptor in skeletal muscles and plays important roles in many physiological activities, such as maintaining posture, regulating movement and controlling speed variation. It has significant clinical relevance and is emerging as a promising therapeutic target for the treatment of motor functional impairment and metabolic diseases. In this review, we summarized muscle spindle distribution and the mechanism of mechanical signal transmission, and reviewed the research progress on morphological and structural characteristics of muscle spindles.

Characterization of afferent corpuscular sensors of the human palmaris brevis muscle.

The palmaris brevis muscle contains numerous muscle spindles to control changes of the muscle length but is devoid of tendon-associated neuronal elements (e.g. Golgi tendon organs or Ruffini-like corpuscles) controlling changes in muscle strength. Pacinian bodies, frequently seen in the palm of the hand, show no direct association to the muscle bundles. The observed innervation pattern of the palmaris brevis muscle points to a specific type of neuronal regulation, present in skeletal muscles with no skeletal connection.

Muscle Spindle Density of Lateral Rotators of the Thigh in Japanese Macaques and a Gibbon.

We examined the six small lateral rotators of the hip joint, which is one of the most flexible joints and allows kinematically complex motions of the hindlimb, to elucidate the functional differentiation among these muscles and to test the hypothesis that species-specific characteristics in hindlimb use during locomotion are reflected in the muscle spindle density and in other parameters of the deep small hip joint rotators. For these purposes, we estimated the number of muscle spindles of the superior gemellus muscle (SG), inferior gemellus muscle, quadratus femoris muscle, obturator internus muscle (OI), obturator externus muscle, and piriformis muscle in three Japanese macaques and a gibbon, using 30-µm-thick serial sections throughout each muscle length after azan staining. The numbers of muscle spindles per 10,000 muscle fibers were determined to compare inter-muscle variation. The spindle density was highest in the SG and lowest in the OI in the Japanese macaques, suggesting that the SG, which is attached to the tendon of the OI, functions as a kinesiological monitor of the OI. On the other hand, SG the was missing in the gibbon, and the OI in the gibbon contained more spindles than that in the Japanese macaques. This suggests that the SG and the OI fused into one muscle in the gibbon. We postulate that the relative importance of the deep small hip rotator muscles differs between the Japanese macaques and gibbon and that the gibbon's muscles are less differentiated in terms of the spindle density, probably because this brachiating species uses its hindlimbs less frequently.

Functional properties of human muscle spindles.

Muscle spindles are ubiquitous encapsulated mechanoreceptors found in most mammalian muscles. There are two types of endings, primary and secondary, and both are sensitive to changes in muscle length and velocity, with the primary endings having a greater dynamic sensitivity. Unlike other mechanoreceptors in the somatosensory system, muscle spindles are unique in possessing motor innervation, via γ-motoneurons (fusimotor neurons), that control their sensitivity to stretch. Much of what we know about human muscles spindles comes from studying the behavior of their afferents via intraneural microelectrodes (microneurography) inserted into accessible peripheral nerves. We review the functional properties of human muscle spindles, comparing and contrasting with what we know about the functions of muscle spindles studied in experimental animals. As in the cat, many human muscle spindles possess a background discharge that is related to the degree of muscle stretch, but mean firing rates are much lower (~10 Hz). They can faithfully encode changes in muscle fascicle length in passive conditions, but higher level extraction of information is required by the central nervous system to measure changes in muscle length during muscle contraction. Moreover, although there is some evidence supporting independent control of human muscle spindles via fusimotor neurons, any effects are modest compared with the clearly independent control of fusimotor neurons observed in the cat.

The human platysma contains numerous muscle spindles.

The mimic muscles are usually described as containing no muscle spindles. In the present publication the human platysma was reinvestigated concerning its content of corpuscular sensors. Serial sections through the platysma of seven donors revealed numerous muscle spindles but no Pacini corpuscules. The muscle spindles were located in the cranial two-thirds of the platysma, and were evenly distributed with a tendency to have more spindles in the lateral part of the muscle. Immunohistochemical staining with S46 antibodies revealed a predominance of nuclear bag fibers. The results point to an extended function of the platysma as an afferent center of the lower face mimic muscles.

The human medial pterygoid muscle: Attachments and distribution of muscle spindles.

Published descriptions about the sites of origin of the human medial pterygoid muscle vary and there are few reports on the distribution and density of muscle spindles in this muscle. We aimed to: (1) determine the extent of anatomical variability in the origins and insertions of the superficial and deep heads of the human medial pterygoid muscle and (2) determine the extent of variation in the distribution of spindles in the two heads of the muscle. Thirty-nine human cadaver hemi-heads were dissected and the attachments of the medial pterygoid muscle examined. The whole muscle was removed, weighed, cut into segments and embedded in wax for light microscopy. Sections were stained with Weigert-Van Gieson stain and scanned into digital images. Spindles were manually counted. In seven specimens, the deep head of the muscle arose from the medial surface of the lateral pterygoid plate and the pterygoid fossa. In 28 specimens, the origin extended onto the lateral surface of the medial pterygoid plate. There were abundant muscle spindles in the middle of the muscle, slightly fewer 1 cm toward the insertion, significantly fewer 1 cm toward the origin, and few or no spindles near the origins of the superficial and deep heads or near their insertion. In conclusion, firstly, this study shows that in 72% of the specimens examined, the origin of the medial pterygoid is wider than conventionally described in anatomical textbooks. Secondly, the segmental distribution of muscle spindles is described for the first time. Clin. Anat. 30:1064-1071, 2017. © 2017 Wiley Periodicals, Inc.

Fibre typing of intrafusal fibres.

The first descriptions of muscle spindles with intrafusal fibres containing striated myofibrils and nervous elements were given approximately 150 years ago. It took, however, another 100 years to establish the presence of two types of intrafusal muscle fibres: nuclear bag and nuclear chain fibres. The present paper highlights primarily the contribution of Robert Banks in fibre typing of intrafusal fibres: the confirmation of the principle of two types of nuclear bag fibres in mammalian spindles and the variation in occurrence of a dense M-band along the fibres. Furthermore, this paper summarizes how studies from the Umeå University group (Laboratory of Muscle Biology in the Department of Integrative Medical Biology) on fibre typing and the structure and composition of M-bands have contributed to the current understanding of muscle spindle complexity in adult humans as well as to muscle spindle development and effects of ageing. The variable molecular composition of the intrafusal sarcomeres with respect to myosin heavy chains and M-band proteins gives new perspectives on the role of the intrafusal myofibrils as stretch-activated sensors influencing tension/stiffness and signalling to nuclei.

Identification of muscle spindles in the submentalis muscle of the marine toad, Bufo marinus and its potential proprioceptive capacity in jaw-tongue coordination.

The muscle spindle has been well studied in mammals, birds, and some reptiles, but little is known about its structure and function in amphibians. Several physiological and behavioral studies in frogs and toads suggest that the submentalis muscle has an important role in jaw-tongue coordination during feeding through sensory feedback mechanisms. Evidence suggests this mechanism is generated through muscle spindles, or spindle-like structures. However, the presence of these has not been investigated. Using charged fluorescent molecules that are taken up by endocytosis at activated synapses, numerous muscle spindles were identified in the submentalis muscle of the marine toad, Bufo marinus. These were further verified with brightfield and differential interference contrast microscopy. The results provide anatomical evidence for muscle spindles in the submentalis muscle and suggest a mechanism for the submentalis muscle's role in jaw-tongue coordination in B. marinus.

[Distribution of the muscle spindles in human masticatory muscles].

OBJECTIVE: To investigate the characteristics in the topographic distribution of the muscle spindles in human masticatory muscles. METHODS: The muscle spindles of the masticatory muscles on both sides of 3 human corpses fixed in formalin for more than 1 year were observed histologically and analyzed quantitatively using an image analysis system. RESULTS: The mean muscle spindle density was 32.11/g in the masseter, significantly higher in the deep muscular fibers (70.76/g) with high proportion of spindle complexes than in the superficial layers of the muscle belly (P<0.05). The mean spindle density in the temporalis was 5.44/g, higher in the anterior portion (7.44/g) than in the posterior portion (3.78/g, P<0.01). The medial pterygoid had a mean spindle density of 4.43/g. CONCLUSION: These results indicate a heterogeneous distribution of muscle spindles in the masticatory muscles with different morphologies or in different portions of the same muscle, depending on muscle fiber type and muscular architecture.

A comparative analysis of the encapsulated end-organs of mammalian skeletal muscles and of their sensory nerve endings.

The encapsulated sensory endings of mammalian skeletal muscles are all mechanoreceptors. At the most basic functional level they serve as length sensors (muscle spindle primary and secondary endings), tension sensors (tendon organs), and pressure or vibration sensors (lamellated corpuscles). At a higher functional level, the differing roles of individual muscles in, for example, postural adjustment and locomotion might be expected to be reflected in characteristic complements of the various end-organs, their sensory endings and afferent nerve fibres. This has previously been demonstrated with regard to the number of muscle-spindle capsules; however, information on the other types of end-organ, as well as the complements of primary and secondary endings of the spindles themselves, is sporadic and inconclusive regarding their comparative provision in different muscles. Our general conclusion that muscle-specific variability in the provision of encapsulated sensory endings does exist demonstrates the necessity for the acquisition of more data of this type if we are to understand the underlying adaptive relationships between motor control and the structure and function of skeletal muscle. The present quantitative and comparative analysis of encapsulated muscle afferents is based on teased, silver-impregnated preparations. We begin with a statistical analysis of the number and distribution of muscle-spindle afferents in hind-limb muscles of the cat, particularly tenuissimus. We show that: (i) taking account of the necessity for at least one primary ending to be present, muscles differ significantly in the mean number of additional afferents per spindle capsule; (ii) the frequency of occurrence of spindles with different sensory complements is consistent with a stochastic, rather than deterministic, developmental process; and (iii) notwithstanding the previous finding, there is a differential distribution of spindles intramuscularly such that the more complex ones tend to be located closer to the main divisions of the nerve. Next, based on a sample of tendon organs from several hind-foot muscles of the cat, we demonstrate the existence in at least a large proportion of tendon organs of a structural substrate to account for multiple spike-initiation sites and pacemaker switching, namely the distribution of sensory terminals supplied by the different first-order branches of the Ib afferent to separate, parallel, tendinous compartments of individual tendon organs. We then show that the numbers of spindles, tendon organs and paciniform corpuscles vary independently in a sample of (mainly) hind-foot muscles of the cat. Grouping muscles by anatomical region in the cat indicated the existence of a gradual proximo-distal decline in the overall average size of the afferent complement of muscle spindles from axial through hind limb to intrinsic foot muscles, but with considerable muscle-specific variability. Finally, we present some comparative data on muscle-spindle afferent complements of rat, rabbit and guinea pig, one particularly notable feature being the high incidence of multiple primary endings in the rat.

Combining frequency and time domain approaches to systems with multiple spike train input and output.

A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods.

Morphologic and morphometrical study of the muscle spindle in muscular dystrophy.

OBJECTIVE: To determine the morphologic and the morphometrical features of spindles in biopsies of patients with different types of muscular dystrophy and investigate the possible involvement of the spindle in the pathologic process of these diseases. STUDY DESIGN: The following variables were studied in biopsy specimens from 10 patients with Duchenne or Becker dystrophy, 9 with limb-girdle dystrophy, 3 with congenital dystrophy and 3 with facioscapulohumeral dystrophy: diameter and area of spindle; thickness of the capsule; number, diameter and area of intrafusal fibers; and number and area of nuclei. RESULTS: The statistical evaluation of the data showed significant differences regarding the thickness of the capsule, which was greater in patients than in controls, while the diameter and the area of the fibers were all smaller in patients than in controls. The area of nuclei of fibers was increased; this was a common feature for all types of muscular dystrophy. CONCLUSION: These findings indicate that the spindle possibly participates in the pathologic process of different types of muscular dystrophies.

Determination of slow-tonic MyHC immunoreactivity is an important step in the evaluation of muscle spindles in porcine extraocular muscles.

We have tested our hypothesis suggesting (i) that for the reliable determination and counting of muscle spindles (Msp) at the light microscopy level in extraocular muscles (EOM), analysis of the spindle specific myosin heavy chain (MyHC) immunoreactivity of intrafusal fibers, especially after staining with anti-slow-tonic MyHC antibodies, is the most convenient tool, (ii) that the number of Msp determined by the slow-tonic MyHC immunoreactivity of intrafusal fibers in EOM is much lower than that based on histological examination and (iii) that the previously reported numbers of Msp based on histological examination of EOM could be overestimated. In order to determine the number and distribution of Msp and to analyze the MyHC isoform immunoreactivity of intrafusal fibers in porcine EOM, paraffin sections of three 9-month-old pig medial (MR) and lateral rectus (LR), levator palpebrae (LP) and retractor bulbi (RB) muscles were stained histologically or using specific monoclonal antibodies (mAbs) against MyHC isoforms. Msp in recti and LP muscles studied by immunocytochemistry contained nuclear bag (NB) fiber(s) reacting with mAbs against slow-tonic, slow-twitch, alpha-cardiac and neonatal MyHCs, but not with the mAb against fast-twitch MyHC, which, on the contrary, stained nuclear chain (NC) fibers. Based on determination of spindle specific slow-tonic MyHC isoform immunoreactivity we have found 72 Msp in the MR and 68 Msp in the LR and 12 Msp in LP muscles, which was only 62, 55 and 32% of the Msp total counts according to histological examination, respectively. In the RB muscle, we have even found only 15 spindle-like-structures composed of encapsulated thin muscle fibers, which possessed only a reaction with anti-fast-twitch MyHC mAb, but lacked slow-tonic, slow-twitch or alpha-cardiac MyHCs immunoreactivity. Our analysis of porcine EOM confirmed the above suggestions, demonstrating, for the first time in the pig, the presence of "false Msp" mimicking encapsulated muscle fibers on histological sections that lack spindle specific MyHC immunoreactivity. In analogy with other muscles we suggest that "false Msp" are not innervated by sensory axons and therefore do not contribute to the physiological sensation of the muscle length changes. Our results thus show that the reliable identification of functionally effective Msp in EOM must involve immunohistochemical analysis of spindle specific MyHC isoforms of intrafusal fibers, as "false" spindles appearing on histologically stained sections as encapsulated muscle fibers could be regarded as "true" Msp and thus increase the spindle number counts in earlier studies.

Age-related physiological and morphological changes of muscle spindles in rats.

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.

An allometric analysis of the number of muscle spindles in mammalian skeletal muscles.

An allometric analysis of the number of muscle spindles in relation to muscle mass in mammalian (mouse, rat, guinea-pig, cat, human) skeletal muscles is presented. It is shown that the trend to increasing number as muscle mass increases follows an isometric (length) relationship between species, whereas within a species, at least for the only essentially complete sample (human), the number of spindles scales, on average, with the square root rather than the cube root of muscle mass. An attempt is made to reconcile these apparently discrepant relationships. Use of the widely accepted spindle density (number of spindles g(-1) of muscle) as a measure of relative abundance of spindles in different muscles is shown to be grossly misleading. It is replaced with the residuals of the linear regression of ln spindle number against ln muscle mass. Significant differences in relative spindle abundance as measured by residuals were found between regional groups of muscles: the greatest abundance is in axial muscles, including those concerned with head position, whereas the least is in muscles of the shoulder girdle. No differences were found between large and small muscles operating in parallel, or between antigravity and non-antigravity muscles. For proximal vs. distal muscles, spindles were significantly less abundant in the hand than the arm, but there was no difference between the foot and the leg.

Morphometric study of the human muscle spindle.

OBJECTIVE: To study the morphometric characteristics of the human muscle spindle in normal muscle and to investigate the influence of aging. STUDY DESIGN: The following variables were studied in 72 spindles: area and diameter of the spindle; thickness of the capsule; number, area and diameter of fibers; and number and area of nuclei. RESULTS: In deltoid and extensor digitorum brevis muscles, a reduction in the diameter of the spindle as a function of age was found, while no statistically significant change in the variables as a function of age was observed in the quadriceps femoris and biceps muscles. In the deltoid, a reduction in the number of fibers and an increase in their diameter were also observed. CONCLUSION: These findings could prove useful in the study of the spindle in relation to disease.

Somatic and intramuscular distribution of muscle spindles and their relation to muscular angiotypes.

The distribution pattern of muscle spindles in the skeletal musculature has been reviewed in a large number of muscles (using the literature data especially from cat and man), and the relation of spindle content to muscle mass was quantitatively examined in 36 cat and 140 human muscles. In both species, the number of spindles increases with increasing muscle mass in a power law fashion of the form y=bx+a, whereby y denotes the logarithm of spindle content within a muscle, and x is the logarithm of muscle mass. For the cat, slope b and intercept a were estimated as 0.39 and 1.53, and for man as 0.48 and 1.33, respectively. The results show that the spindle content of a muscle may be related to its mass, confirming a similar analysis made previously by Banks and Stacey (Mechano receptors, Plenum Press, New York, 1988, pp. 263-269) in a different data set. With regard to the histological profile of muscle fibers, (as it is already well documented by many groups) muscle spindles tend to be located in deeper muscle regions where oxidative fibers predominate, and are far scarcer in superficial and flat muscle regions where glycolytic fibers predominate. These discrete muscle regions differ also in the properties of the vessel tree supplying them, for which the term oxidative and glycolytic "angiotype" has been used. The results from these three aspects of analysis (relation to muscle mass, relation to muscle regions with high oxidative index and relation to muscle regions with dense vascular supply) were combined with histological findings showing that spindles may be in systematic anatomical contact to intramuscular vessels. Based on these data a hypothesis is proposed according to which, both the number and intramuscular placement of muscle spindles are related to the oxidative angiotype supplying the muscle territories rich in oxidative fibers. The hypothesis is discussed.

Anatomy and fiber type composition of human interarytenoid muscle.

Intrinsic laryngeal muscle investigations, especially those of the interarytenoid (IA) muscle, have been primarily teleologically based. We determined IA muscle anatomy and histochemical and immunohistochemical classification of extrafusal and intrafusal (muscle spindle) fibers in 5 patients. Extrafusal fibers were oxidative type I and glycolytic types IIA and IIX. Intrafusal fibers of muscle spindles were identified by the presence of tonic and neonatal myosin. The results demonstrate that the IA muscle has a phenotype similar to that of limb skeletal muscle. Myosin coexpression, the absence of intrafusal fibers, and fiber type grouping were unusual features found previously in the thyroarytenoid and posterior cricoarytenoid muscles, but they were not present in the IA muscle. These findings lead to the conclusion that the IA muscle has functional significance beyond its assumed importance in maintaining vocal fold position during phonation. The presence of spindles demonstrates differences in motor control as compared to the thyroarytenoid and posterior cricoarytenoid muscles. Further, extrafusal fiber characteristics implicate IA muscle involvement in muscle tension dysphonia and adductor spasmodic dysphonia. Given the unique physiologic characteristics of the human IA muscle, further research into the role of the IA muscle in voice disorders is warranted.