Intrafusal Research Articles

Egr3-dependent muscle spindle stretch receptor intrafusal muscle fiber differentiation and fusimotor innervation homeostasis.

Muscle stretch proprioceptors (muscle spindles) are required for stretch reflexes and locomotor control. Proprioception abnormalities are observed in many human neuropathies, but the mechanisms involved in establishing and maintaining muscle spindle innervation and function are still poorly understood. During skeletal muscle development, sensory (Ia-afferent) innervation induces contacted myotubes to transform into intrafusal muscle fibers that form the stretch receptor core. The transcriptional regulator Egr3 is induced in Ia-afferent contacted myotubes by Neuregulin1 (Nrg1)/ErbB receptor signaling and it has an essential role in spindle morphogenesis and function. Because Egr3 is widely expressed during development and has a pleiotropic function, whether Egr3 functions primarily in skeletal muscle, Ia-afferent neurons, or in Schwann cells that myelinate Ia-afferent axons remains unresolved. In the present studies, cell-specific ablation of Egr3 in mice showed that it has a skeletal muscle autonomous function in stretch receptor development. Moreover, using genetic tracing, we found that Ia-afferent contacted Egr3-deficient myotubes were induced in normal numbers, but their development was blocked to generate one to two shortened fibers that failed to express some characteristic myosin heavy chain (MyHC) proteins. These "spindle remnants" persisted into adulthood, remained innervated by Ia-afferents, and expressed neurotrophin3 (NT3), which is required for Ia-afferent neuron survival. However, they were not innervated by fusimotor axons and they did not express glial derived neurotrophic factor (GDNF), which is essential for fusimotor neuron survival. These results demonstrate that Egr3 has an essential role in regulating gene expression that promotes normal intrafusal muscle fiber differentiation and fusimotor innervation homeostasis.

Football practice and urinary incontinence: Relation between morphology, function and biomechanics

Current evidence points to a high prevalence of urinary incontinence among female athletes. In this context, this study aims to assess if structural and biomechanical characteristics of the pubovisceral muscles may lead to urine leakage. Clinical and demographic data were collected, as well as pelvic Magnetic Resonance Imaging. Furthermore, computational models were built to verify if they were able to reproduce similar biomechanical muscle response as the one measured by dynamic imaging during active contraction by means of the percent error. Compared to the continent ones (n=7), incontinent athletes (n=5) evidenced thicker pubovisceral muscles at the level of the midvagina (p=0.019 and p=0.028 for the right and left sides, respectively). However, there were no differences neither in the strength of contraction in the Oxford Scale or in the displacement of the pelvic floor muscles during simulation of voluntary contraction, which suggests that urine leakage may be related with alterations in the intrafusal fibers than just the result of thicker muscles. Additionally, we found similar values of displacement retrieved from dynamic images and numerical models (6.42±0.36mm vs. 6.10±0.47mm; p=0.130), with a percent error ranging from 1.47% to 17.20%. However, further refinements in the mechanical properties of the striated skeletal fibers of the pelvic floor muscles and the inclusion of pelvic organs, fascia and ligaments would reproduce more realistically the pelvic cavity.

Muscle spindles exhibit core lesions and extensive degeneration of intrafusal fibers in the Ryr1I4895T/wt mouse model of core myopathy

Muscle spindles from the hind limb muscles of adult Ryr1I4895T/wt (IT/+) mice exhibit severe structural abnormalities. Up to 85% of the spindles are separated from skeletal muscle fascicles by a thick layer of connective tissue. Many intrafusal fibers exhibit degeneration, with Z-line streaming, compaction and collapse of myofibrillar bundles, mitochondrial clumping, nuclear shrinkage and pyknosis. The lesions resemble cores observed in the extrafusal myofibers of this animal model and of core myopathy patients. Spindle abnormalities precede those in extrafusal fibers, indicating that they are a primary pathological feature in this murine Ryr1-related core myopathy. Muscle spindle involvement, if confirmed for human core myopathy patients, would provide an explanation for an array of devastating clinical features characteristic of these diseases and provide novel insights into the pathology of RYR1-related myopathies.

A biomechanical device for human sensorimotor function

T muscle spindle and its associated sensory neurons form the afferent sensorimotor circuit of motor function. In order to better understand the physiology of this circuit so as to use it to address its relevant diseases; this study aims to establish an in vitro model of this spindle-sensory unit by integrating the cells comprising this system with microelectromechanical (MEMS) technology. A defined cell culture system has been developed to support the in vitro differentiation of human intrafusal muscle fibers (muscle fibers inside the muscle spindle) and human proprioceptive sensory neurons as well as their connections. A BioMEMS chip has been designed and fabricated to allow for the integration and functional analysis of this biological system. Intrafusal muscle fibers have been grown and activated by controlled stretching of the cantilever sensor. This non-invasive test bed will allow for controlled and long-term monitoring, interrogation and high control analysis of the sensorimotor unit of the human neuromuscular reflex arc. It could have use for applications not only for emulation of human health and disease, but also for the construction of relevant robotic systems.

How does the structure of extraocular muscles and their nerves affect their function?

The sensory and motor control of human extraocular muscles (EOMs) have been subjected to considerable speculation in ophthalmic literature, often related to infranuclear structures such as the unique complement of muscle fibres and their associated sensory organs. The intrafusal fibres do not resemble their somatic counterparts and their peculiar morphology has raised questions about their proprioceptive capacity. No Golgi tendon organs have so far been observed and the myotendinous nerve endings, previously assumed to convey sensory information, have recently been argued to merely represent constituents of the efferent innervation serving the multiply innervated muscles fibres. These observations raise questions about the overall capacity to monitor the activity created by the generous efferent nerve supply observed in these muscles. Furthermore, the argued independent activity of muscular layers and compartments suggest that the required feedback must be highly structured and more specific than previously assumed. Yet, uncertainty about the source of such information remains. The purpose of this paper is to provide a short review of neuromuscular properties of human extraocular muscles. Their functional implications and the most reputable sources of proprioception will also be discussed. The promoted views are based on pertinent literature and previous research undertaken by the authors.

Differential regulation of AChR clustering in the polar and equatorial region of murine muscle spindles.

Intrafusal fibers of muscle spindles are innervated in the central region by afferent sensory axons and at both polar regions by efferent γ-motoneurons. We previously demonstrated that both neuron-muscle contact sites contain cholinergic synapse-like specialisation, including aggregates of the nicotinic acetylcholine receptor (AChR). In this study we tested the hypothesis that agrin and its receptor complex (consisting of LRP4 and the tyrosine kinase MuSK) are involved in the aggregation of AChRs in muscle spindles, similar to their role at the neuromuscular junction. We show that agrin, MuSK and LRP4 are concentrated at the contact site between the intrafusal fibers and the sensory- and γ-motoneuron, respectively, and that they are expressed in the cell bodies of proprioceptive neurons in dorsal root ganglia. Moreover, agrin and LRP4, but not MuSK, are expressed in γ-motoneuron cell bodies in the ventral horn of the spinal cord. In agrin- and in MuSK-deficient mice, AChR aggregates are absent from the polar regions. In contrast, the subcellular concentration of AChRs in the central region where the sensory neuron contacts the intrafusal muscle fiber is apparently unaffected. Skeletal muscle-specific expression of miniagrin in agrin(-/-) mice in vivo is sufficient to restore the formation of γ-motoneuron endplates. These results show that agrin and MuSK are major determinants during the formation of γ-motoneuron endplates but appear dispensable for the aggregation of AChRs at the central region. Our results therefore suggest different molecular mechanisms for AChR clustering within two domains of intrafusal fibers.

Muscle thixotropy as a tool in the study of proprioception.

When a muscle relaxes after a contraction, cross-bridges between actin and myosin in sarcomeres detach, but about 1% spontaneously form new, non-force-generating attachments. These bridges give muscle its thixotropic property. They remain in place for long periods if the muscle is left undisturbed and give the muscle a passive stiffness in response to a stretch. They are detached by stretch, but reform at the new length. If the muscle is then shortened, the presence of these bridges prevents muscle fibres from shortening and they fall slack. So, resting muscle can be in one of two states, where it presents in response to a stretch with a high stiffness, if no slack is present, or with a compliant response in the presence of slack. Intrafusal fibres of muscle spindles show thixotropic behaviour. For spindles, after a conditioning contraction, they are left stretch sensitive, with a high level of background discharge. Alternatively, if after the contraction the muscle is shortened, intrafusal fibres fall slack, leaving spindles with a low level of background activity and insensitivity to stretch. Muscle spindles are receptors involved in the senses of human limb position and movement. The technique of muscle conditioning can be used to help understand the contribution of muscle spindles to these senses and how the brain interprets signals arising in spindles. When, in a two-arm position-matching task, elbow muscles of the two arms are deliberately conditioned in opposite ways, the blindfolded subject makes large position errors of which they are unaware. The evidence suggests that the brain is concerned with the difference signal coming from the antagonists acting at the elbow and with the overall difference in signal from the two arms. Another way of measuring position sense is to use a single arm and indicate its perceived position with a pointer. Here, there is no access to a signal from the other limb, and position sense relies on referral to a central map of the body, the postural schema.

Formation of cholinergic synapse-like specializations at developing murine muscle spindles

Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of specialized skeletal muscle fibers, called intrafusal fibers, which are innervated in the central (equatorial) region by afferent sensory axons and in both polar regions by efferent γ-motoneurons. We show that AChRs are concentrated at the γ-motoneuron endplate as well as in the equatorial region where they colocalize with the sensory nerve ending. In addition to the AChRs, the contact site between sensory nerve ending and intrafusal muscle fiber contains a high concentration of choline acetyltransferase, vesicular acetylcholine transporter and the AChR-associated protein rapsyn. Moreover, bassoon, a component of the presynaptic cytomatrix involved in synaptic vesicle exocytosis, is present in γ-motoneuron endplates but also in the sensory nerve terminal. Finally, we demonstrate that during postnatal development of the γ-motoneuron endplate, the AChR subunit stoichiometry changes from the γ-subunit-containing fetal AChRs to the ε-subunit-containing adult AChRs, similar and approximately in parallel to the postnatal subunit maturation at the neuromuscular junction. In contrast, despite the onset of ε-subunit expression during postnatal development the γ-subunit remains detectable in the equatorial region by subunit-specific antibodies as well as by analysis of muscle spindles from mice with genetically-labeled AChR γ-subunits. These results demonstrate an unusual maturation of the AChR subunit composition at the annulospiral endings and suggest that in addition to the recently described glutamatergic secretory system, the sensory nerve terminals are also specialized for cholinergic synaptic transmission, synaptic vesicle storage and exocytosis.

Distribution of caveolin in the muscle spindles of human skeletal muscle

The aim of the present study was to demonstrate the location of the different members of the caveolin (cav) family in human muscle spindles. Twenty spindles of three human muscles (vastus medialis, ischiocavernosus, bulbospongiosus) from 12 cadavers were immunohistochemically stained for cav-1, cav-2, and cav-3, and the equatorial and polar regions evaluated. All layers of the outer and inner spindle capsule and all blood vessels within the spindle stained for cav-1 and cav-2. In the muscle spindle, intrafusal muscle fibres stained selectively for cav-3, but with a patchy appearance. Caveolinopathies may therefore also include changes in muscle spindle function.

The Erk MAP kinase pathway is activated at muscle spindles and is required for induction of the muscle spindle‐specific gene Egr3 by neuregulin1

Muscle spindles are sensory receptors composed of specialized muscle fibers, known as intrafusal muscle fibers, along with the endings of sensory neuron axons that innervate these muscle fibers. Formation of muscle spindles requires neuregulin1 (NRG1), which is released by sensory axons, activating ErbB receptors in muscle cells that are contacted. The transcription factor Egr3 is transcriptionally induced by NRG1, which in turn activates various target genes involved in forming intrafusal fibers. We have previously shown that, in cultured muscle cells, NRG1 signaling activates the Egr3 gene through SRF and CREB, which bind to a composite regulatory element, and that NRG1 signaling targets SRF by stimulating nuclear translocation of SRF coactivators myocardin-related transcription factor (MRTF)-A and MRTF-B and targets CREB by phosphorylation. The current studies examined signaling relays that might function in the NRG1 pathway upstream of SRF and CREB. We found that transcriptional induction of Egr3 in response to NRG1 requires the MAP kinase Erk1/2, which acts upstream of CREB to induce its phosphorylation. MRTFs are targeted by the Rho-actin pathway, yet in the absence of Rho-actin signaling, even though MRTFs fail to be translocated to the nucleus, NRG1 induces Egr3 transcription. In mouse muscle in vivo, activation of Erk1/2 is enhanced selectively where muscle spindles are located. These results suggest that Erk1/2 acts in intrafusal fibers of muscle spindles to induce transcription of Egr3 and that Egr3 induction occurs independently of MRTFs and involves Erk1/2 acting on other transcriptional regulatory targets that interact with the SRF-CREB regulatory element.

The Sensory Innervation of the Human Pharynx: Searching for Mechanoreceptors

The coordinate neural regulation of the upper airways muscles is basic to control airway size and resistance. The superior constrictor pharyngeal muscle (SCPM) forms the main part of the lateral and posterior walls of the pharynx and typically is devoid of muscle spindles, the main type of proprioceptor. Because proprioception arising from SCPM is potentially important in the physiology of the upper airways, we have investigated if there are mechanical sensory nerve endings substitute for the muscle spindles. Samples of human pharynx were analyzed using immunohistochemistry associated to general axonic and Schwann cells markers (NSE, PGP 9.5, RT-97, and S100P), intrafusal muscle fiber markers, and putative mechanical sense proteins (TRPV4 and ASIC2). Different kinds of sensory corpuscles were observed in the pharynx walls (Pacini-like corpuscles, Ruffini-like corpuscles, spiral-wharves nerve structures, and others) which are supplied by sensory nerves and express putative mechanoproteins. No evidence of muscle spindles was observed. The present results demonstrate the occurrence of numerous and different morphotypes of sensory corpuscles/mechanoreceptors in human pharynx that presumably detect mechanical changes in the upper airways and replace muscle spindles for proprioception. Present findings are of potential interest for the knowledge of pathologies of the upper airways with supposed sensory pathogenesis.

Muscle Spindles

Based on a Dissertation presented to the Society on 6th November, 1964The action of our muscles is controlled with a remarkable delicacy, and components of the nervous system at every level contribute to this. On the afferent side, the stretch receptors of muscle spindles are the most peripheral elements and have been known to histologists and physiologists for more than a century, Hassall must receive the credit for the discovery of muscle spindles in 1851, but the first systematic description was Weissmann’s in 1861. Each spindle consists of a parallel bundle of striated muscle fibres—intrafusal fibres. The bundle is 7 to 12 mm. long, and is surrounded by what Sherrington later called the lymph space, because he was able to inject it with dye via the lymph vessels: this space is enclosed by a thin fibrous capsule. The intrafusal fibres vary in their length and diameter, and are attached to one another at their ends; the ends of the longest fibres are attached to extrafusal endomysium. The spindle is supplied with nerves of various diameters terminating in different types of ending on the intrafusal fibres.

Analyses of muscle spindles in the soleus of six inbred mouse strains

Adult muscle size and fibre-type composition are heritable traits that vary substantially between individuals. We used inbred mouse strains in which soleus muscle mass varied by an order of magnitude to explore whether properties of muscle spindles can also be influenced by genetic factors. Skip-serial cross-sections of soleus muscles dissected from 15 male mice of BEH, BEL, C57BL/6J, DUH, LG/J and SM/J strains were analysed for number of muscle spindles and characteristics of intrafusal and extrafusal fibres following ATPase staining. The BEL and DUH strains determined the range of: soleus mean size, a 10-fold difference from 2.1 to 22.3 mg, respectively; the mean number of extrafusal fibres, a 2.5-fold difference from 497 to 1249; and mean fibre-cross-sectional area, three-fold difference, e.g. for type 1 fibres, from 678 to 1948 μm². The range of mean proportion of type 1 fibres was determined by C57BL/6J (31%) and DUH (64%) strains. The mean number of spindles per muscle ranged between nine (LG/J) and 13 (BEL) (strain effect P < 0.02). Genetic correlations between spindle count and muscle weight or properties of extrafusal fibres were weak and not statistically significant. However, there was a strong correlation between the proportion of spindles with more than one bag2 fibre and the proportion of extrafusal fibres that were of type 1, and strain-dependent variation in the numbers of such spindles was statistically significant. The numbers of intrafusal fibres per spindle ranged from 2 to 8, with the most common complement of four found in 75.6% of spindles. There were no significant differences between the strains in the mean numbers of intrafusal fibres; however, the variance of the number was significantly less for the C57BL/6J strain than for any of the others. We conclude that abundance of muscle spindles and their intrafusal-fibre composition are substantially determined by genetic factors, which are different from those affecting muscle size and properties of the extrafusal fibres.

Egr3‐dependent muscle stretch receptor morphogenesis and innervation homeostasis

Muscle spindles are skeletal muscle receptors that mediate stretch reflexes and proprioception in vertebrates. Proprioception abnormalities are observed in many human neuropathies with unknown etiology and factors involved in sensory nerve‐stretch receptor homeostasis are poorly understood. During skeletal muscle development, sensory (Ia‐afferent) innervation is restricted to only a few myotubes which induces their transformation into intrafusal muscle fibers that form the stretch receptor core. The transcriptional regulator Egr3 is induced by sensory innervation and it has an essential role in stretch receptor morphogenesis, but whether its function is restricted to developing receptors and whether it has a role in innervation homeostasis is not known. Ablation of Egr3 using skeletal muscle specific knockout mice demonstrated its autonomous function in developing stretch receptors. Lineage tracing experiments using Egr3‐Cre knock‐in mice showed that stretch receptor differentiation is blocked in the absence of Egr3 and innervation fails to be maintained. Thus, Egr3 has an essential function in intrafusal muscle fiber differentiation and gene regulation required to maintain innervation homeostasis. (Support: NIH R01‐NS063078 and K26‐OD010945).

Botulinum neurotoxin treatment improves force regulation in writer's cramp

Writer's cramp patients show poor force regulation during handwriting, but also in other experimental tasks requiring fine motor control. Botulinum neurotoxin (BoNT) treatment is clinically effective in a substantial portion of writer's cramp patients, but the full mechanism of action remains enigmatic. BoNT possibly influences α- and γ-motoneurons through chemodenervation not only of extra-, but also intrafusal muscle fibres and might thus influence muscle spindle afferents. Hence, BoNT weakens injected muscles, but may also modulate sensory aspects of force control. Ten patients and 18 controls pressed their index finger on a force sensor tracking two visual targets: The first target consisted of five plateaus with successively higher force levels and alternated with ascending ramps. In the second target condition the same successive plateaus were to be reached by abrupt jumps. The generated force displayed as a time dependant curve. Root mean square of the difference between target and produced force level was calculated for each plateau/ramp/jump. Patients were treated with BoNT at week 4 and measured at baseline, weeks 2, 4, 6 and 8. Disturbed force regulation in patients for the plateaus and the second jump at baseline resolved after BoNT treatment, and the root mean square of force deviation decreased for the ramps. Fine force control was within the 95% confidence interval of the control group after treatment. In conclusion, force regulation was disturbed in patients and improved after BoNT treatment. This is not compatible with a simple muscle weakening and might thus reflect improved sensorimotor integration.

Intrafusal effects of botulinum toxin injections for spasticity: Revisiting a previous paper

Botulinum toxin, frequently used to manage focal limb spasticity, has been reported to affect both extrafusal and intrafusal fibers of the injected muscle. Since most studies have used spinal reflexes, it is difficult to isolate the intrafusal effects from extrafusal and central effects. In a paper by On et al. [7], both stretch and H-reflexes were used to examine the intrafusal effects of botulinum toxin injections. Revisiting the data from On et al. [7] presented a unique opportunity to describe a novel method of measuring the effect of botulinum toxin-A on muscle spindle activity in patients with spasticity. H-reflex, maximum M-wave, and Achilles tendon reflex were serially assessed in ten patients with stroke pre-, 2, 4, and 12 weeks post-botulinum. In order to assess the intrafusal effects, we subtracted the %change in H-reflex amplitude from baseline (representing extrafusal and central effects) from the %change in Achilles tendon reflex amplitude from baseline (representing intrafusal, extrafusal and central effects). Using this formula, our results suggest that botulinum induces significant chemodenervation of the intrafusal muscle fibers (33% decreases). Intrafusal effects were greatest at 2 weeks, but tapered off by 12 weeks post-botulinum (p<0.017). We found a significant positive correlation between the intrafusal effects of botulinum toxin and changes in modified Ashworth scale. Our method of assessing the effects of botulinum toxin shows significant effect on intrafusal fibers, which correlates with clinical manifestation of spasticity. Future studies need to investigate ways to maximize intrafusal effects and minimize extrafusal effects of botulinum therapy.

Neuregulin1 signaling targets SRF and CREB and activates the muscle spindle-specific gene Egr3 through a composite SRF–CREB-binding site

Muscle spindles are sensory receptors embedded within muscle that detect changes in muscle length. Each spindle is composed of specialized muscle fibers, known as intrafusal muscle fibers, along with the endings of axons from sensory neurons that innervate these muscle fibers. Formation of muscle spindles requires neuregulin1 (NRG1), which is released by sensory axons, activating ErbB receptors in muscle cells that are contacted. In muscle cells, the transcription factor Egr3 is transcriptionally induced by NRG1, which in turn activates various target genes involved in forming the intrafusal fibers of muscle spindles. The signaling relay within the NRG1–ErbB pathway that acts to induce Egr3 is presumably critical for muscle spindle formation but for the most part has not been determined. In the current studies, we examined, using cultured muscle cells, transcriptional regulatory mechanisms by which Egr3 responds to NRG1. We identified a composite regulatory element for the Egr3 gene, consisting adjacent sites that bind cAMP response element binding protein (CREB) and serum response factor (SRF), with a role in NRG1 responsiveness. The SRF element also influences Egr3 basal expression in unstimulated myotubes, and in the absence of the SRF element, the CREB element influences basal expression. We show that NRG1 signaling, to target SRF, acts on the SRF coactivators myocardian-related transcription factor (MRTF)-A and MRTF-B, which are known to activate SRF-mediated transcription, by stimulating their translocation from the cytoplasm to the nucleus. CREB is phosphorylated, which is known to contribute to its activation, in response to NRG1. These results suggest that NRG1 induces expression of the muscle spindle-specific gene Egr3 by stimulating the transcriptional activity of CREB and SRF.

Intrafusal myosin heavy chain expression of human masseter and biceps muscles at young age shows fundamental similarities but also marked differences

Muscle spindles are skeletal muscle mechanoreceptors that provide proprioceptive information to the central nervous system. The human adult masseter muscle has greater number, larger and more complex muscle spindles than the adult biceps. For a better knowledge of muscle diversity and physiological properties, this study examined the myosin heavy chain (MyHC) expression of muscle spindle intrafusal fibres in the human young masseter and young biceps muscles by using a panel of monoclonal antibodies (mAbs) against different MyHC isoforms. Eight MyHC isoforms were detected in both muscles-slow-tonic, I, IIa, IIx, foetal, embryonic, α-cardiac and an isoform not previously reported in intrafusal fibres, termed IIx'. Individual fibres co-expressed 2-6 isoforms. MyHC-slow tonic separated bag1, AS-bag1 and bag2 fibres from chain fibres. Typically, bag fibres also expressed MyHC-I and α-cardiac, whereas chain fibres expressed IIa and foetal. In the young masseter 98% of bag1 showed MyHC-α cardiac versus 30% in the young biceps, 35% of bag2 showed MyHC-IIx' versus none in biceps, 17% of the chain fibres showed MyHC-I versus 61% in the biceps. In conclusion, the result showed fundamental similarities in intrafusal MyHC expression between young masseter and biceps, but also marked differences implying muscle-specific proprioceptive control, probably related to diverse evolutionary and developmental origins. Finding of similarities in MyHC expression between young and adult masseter and biceps muscle spindles, respectively, in accordance with previously reported similarities in mATPase fibre type composition suggest early maturation of muscle spindles, preceding extrafusal fibres in growth and maturation.

Biological characteristics of structural and functional remodelling in skeletal muscle: effect of exercise

For more than one and a half century, the effect of locomotory activity on skeletal muscle structure and function has been studied. It is clear that these changes depend on the mode of activity. Resistance and endurance exercise training differ in their intensity and duration as well as effects on metabolic pathways, structures of skeletal muscle, protein synthesis and degradation rate, neuromuscular junctions and muscle spindles. The purpose of this review was to compare differences and similarities in structural-functional rearrangements in skeletal muscle in endurance and resistance training and the effect of these changes on endurance and strength capacity. The main purpose of the study was to compare changes in mitochondrial and myofibrillar compartments and also changes in neuromuscular junctions in extra- and intrafusal muscle fibers. The comparison of morpho-functional changes in different skeletal muscle fiber types may help an

Using vertebral movement and intact paraspinal muscles to determine the distribution of intrafusal fiber innervation of muscle spindle afferents in the anesthetized cat

Increasing our knowledge regarding intrafusal fiber distribution and physiology of paraspinal proprioceptors may provide key insights regarding proprioceptive deficits in trunk control associated with low back pain and lead to more effective clinical intervention. The use of vertebral movement as a means to reliably stretch paraspinal muscles would greatly facilitate physiological study of paraspinal muscle proprioceptors where muscle tendon isolation is either very difficult or impossible. The effects of succinylcholine (SCh) on 194 muscle spindle afferents from lumbar longissimus or multifidus muscles in response to computer-controlled, ramp-and-hold movements of the L(6) vertebra were investigated in anesthetized cats. Paraspinal muscles were stretched by moving the L(6) vertebra 1.5-1.7mm in the dorsal-ventral direction. Initial frequency (IF), dynamic difference (DD), their changes (∆) following SCh injection (100-400μgkg(-1)), and post-SCh dynamic difference (SChDD) were measured. Muscle spindle intrafusal fiber terminations were classified as primary or secondary fibers as well as bag(1) (b(1)c), bag(2) (b(2)c), b(1)b(2)c, or chain (c) fibers. Intrafusal fiber subpopulations were distinguished using logarithmic transformation of SChDD and ∆IF distributions as established by previous investigators. Increases in DD indicate strength of b(1)c influence while increases in IF indicate strength of b(2)c influence. Out of 194 afferents, 46.9% of afferents terminated on b(2)c fibers, 46.4% on b(1)b(2)c fibers, 1% on b(1)c fibers, and 5.7% terminated on c fibers. Based on these intrafusal fiber subpopulation distributions, controlled vertebral movement can effectively substitute for direct tendon stretch and allow further investigation of paraspinal proprioceptors in this anatomically complex body region.