Endings Of Muscle Spindles Research Articles

Secondary endings of muscle spindles: Structure, reflex action, role in motor control and proprioception.

What is the topic of this review? We describe the structure and function of secondary sensory endings of muscle spindles, their reflex action and role in motor control and proprioception. What advances does it highlight? In most mammalian skeletal muscles, secondary endings of spindles are more or much more numerous than primary endings but are much less well studied. By focusing on secondary endings in this review, we aim to redress the balance, draw attention to what is not known and stimulate future research. Kinaesthesia and the control of bodily movement rely heavily on the sensory input from muscle spindles. Hundreds of these sensory structures are embedded in mammalian muscles. Each spindle has one or more sensory endings and its own complement of small muscle fibres that are activated by the CNS via fusimotor neurons, providing efferent control of sensory responses. Exactly how the CNS wields this influence remains the subject of much fascination and debate. There are two types of sensory endings, primary and secondary, with differing development, morphology, distribution and responsiveness. Spindle primary endings have received more attention than secondaries, although the latter usually outnumber them. This review focuses on the secondary endings. Their location within the spindle, their response properties, the projection of their afferents within the CNS and their reflex actions all suggest that secondaries have certain separate roles from the primaries in proprioception and motor control. Specifically, spindle secondaries seem more adapted than primaries to signalling slow and maintained changes in the relative position of bodily segments, thereby contributing to position sense, postural control and static limb positioning. By highlighting, in this way, the roles of secondary endings, a final aim of the review is to broaden understanding of muscle spindles more generally and of the important contributions they make to both sensory and motor mechanisms.

Microneurography from the posterior tibial nerve: a novel method of recording activity from the foot in freely standing humans.

The posterior tibial nerve, located behind the medial malleolus of the ankle, supplies the intrinsic muscles of the foot and most of the skin of the sole. We describe a novel approach for recording from this nerve via a percutaneously inserted tungsten microelectrode and provide examples of recordings from presumed muscle spindle endings recorded in freely standing human subjects. The fact that the angular excursions of the ankle joint are small as the foot is loaded during the transition from the seated position to standing means that one can obtain stable recordings of neural traffic in unloaded, loaded, and freely standing conditions. We conclude that this novel approach will allow studies that will increase our understanding of the roles of muscle and cutaneous afferents in the foot in the control of upright posture. NEW & NOTEWORTHY We have performed the first microneurographic studies from the posterior tibial nerve at the ankle. Stability of the recording site allows one to record from muscle spindles in the intrinsic muscles of the foot as well as from cutaneous mechanoreceptors in the sole of the foot during the transition from seated to standing. This novel approach opens up new opportunities for studying the roles of muscle and cutaneous afferents in the foot in the control of upright stance.

Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles.

Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV1.1, predominantly in sensory terminals together with NaV1.6 and for NaV1.7, mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles.NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site involved in transduction or encoding of muscle stretch. We propose that NaVs contribute to multiple steps in sensory signaling by muscle spindles as it does in other types of slowly adapting sensory neurons.

Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis–causing mutations

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1G93A and TDP43A315T transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1G93A and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at α‐motor axons in SOD1G93A mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in α‐motor axons in TDP43A315T transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on α‐motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS‐causing mutations, with pathological changes starting at their peripheral nerve endings. J. Comp. Neurol. 523:2477–2494, 2015. © 2015 Wiley Periodicals, Inc.

Degeneration of proprioceptive sensory nerve endings in mice harboring amyotrophic lateral sclerosis-causing mutations.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily targets the motor system. Although much is known about the effects of ALS on motor neurons and glial cells, little is known about its effect on proprioceptive sensory neurons. This study examines proprioceptive sensory neurons in mice harboring mutations associated with ALS, in SOD1(G93A) and TDP43(A315T) transgenic mice. In both transgenic lines, we found fewer proprioceptive sensory neurons containing fluorescently tagged cholera toxin in their soma five days after injecting this retrograde tracer into the tibialis anterior muscle. We asked whether this is due to neuronal loss or selective degeneration of peripheral nerve endings. We found no difference in the total number and size of proprioceptive sensory neuron soma between symptomatic SOD1(G93A) and control mice. However, analysis of proprioceptive nerve endings in muscles revealed early and significant alterations at Ia/II proprioceptive nerve endings in muscle spindles before the symptomatic phase of the disease. Although these changes occur alongside those at α-motor axons in SOD1(G93A) mice, Ia/II sensory nerve endings degenerate in the absence of obvious alterations in α-motor axons in TDP43(A315T) transgenic mice. We next asked whether proprioceptive nerve endings are similarly affected in the spinal cord and found that nerve endings terminating on α-motor neurons are affected during the symptomatic phase and after peripheral nerve endings begin to degenerate. Overall, we show that Ia/II proprioceptive sensory neurons are affected by ALS-causing mutations, with pathological changes starting at their peripheral nerve endings.

A study of the expression of small conductance calcium-activated potassium channels (SK1-3) in sensory endings of muscle spindles and lanceolate endings of hair follicles in the rat.

Processes underlying mechanotransduction and its regulation are poorly understood. Inhibitors of Ca2+-activated K+ channels cause a dramatic increase in afferent output from stretched muscle spindles. We used immunocytochemistry to test for the presence and location of small conductance Ca2+-activated K+ channels (SK1-3) in primary endings of muscle spindles and lanceolate endings of hair follicles in the rat. Tissue sections were double immunolabelled with antibodies to one of the SK channel isoforms and to either synaptophysin (SYN, as a marker of synaptic like vesicles (SLV), present in many mechanosensitive endings) or S100 (a Ca2+-binding protein present in glial cells). SK channel immunoreactivity was also compared to immunolabelling for the Na+ ion channel ASIC2, previously reported in both spindle primary and lanceolate endings. SK1 was not detected in sensory terminals of either muscle spindles or lanceolate endings. SK2 was found in the terminals of both muscle spindles and lanceolate endings, where it colocalised with the SLV marker SYN (spindles and lanceolates) and the satellite glial cell (SGC) marker S100 (lanceolates). SK3 was not detected in muscle spindles; by contrast it was present in hair follicle endings, expressed predominantly in SGCs but perhaps also in the SGC: terminal interface, as judged by colocalisation statistical analysis of SYN and S100 immunoreactivity. The possibility that all three isoforms might be expressed in pre-terminal axons, especially at heminodes, cannot be ruled out. Differential distribution of SK channels is likely to be important in their function of responding to changes in intracellular [Ca2+] thereby modulating mechanosensory transduction by regulating the excitability of the sensory terminals. In particular, the presence of SK2 throughout the sensory terminals of both kinds of mechanoreceptor indicates an important role for an outward Ca2+-activated K+ current in the formation of the receptor potential in both types of ending.

Mechanotransduction in the muscle spindle.

The focus of this review is on the principal sensory ending of the mammalian muscle spindle, known as the primary ending. The process of mechanosensory transduction in the primary ending is examined under five headings: (i) action potential responses to defined mechanical stimuli—representing the ending's input–output properties; (ii) the receptor potential—including the currents giving rise to it; (iii) sensory-terminal deformation—measurable changes in the shape of the primary-ending terminals correlated with intrafusal sarcomere length, and what may cause them; (iv) putative stretch-sensitive channels—pharmacological and immunocytochemical clues to their identity; and (v) synaptic-like vesicles—the physiology and pharmacology of an intrinsic glutamatergic system in the primary and other mechanosensory endings, with some thoughts on the possible role of the system. Thus, the review highlights spindle stretch-evoked output is the product of multi-ionic receptor currents plus complex and sophisticated regulatory gain controls, both positive and negative in nature, as befits its status as the most complex sensory organ after the special senses.Electronic supplementary materialThe online version of this article (doi:10.1007/s00424-014-1536-9) contains supplementary material, which is available to authorized users.

Immunohistochemical localization of the GM1, GD1a, GD1b and GQ1b gangliosides in the neuronal endings of rat muscle spindles

Immunohistochemical localization of the GM1, GD1a, GD1b and GQ1b gangliosides in the neuronal endings of rat muscle spindles

Modulation of baroreceptor afferent terminal excitability and reflex responses by phospholipase D‐coupled metabotropic glutamate receptors

We have demonstrated glutamate released from clear synaptic‐like vesicles (SLVs) modulates mechanoreceptor excitability in Ia primary afferent endings of rat muscle spindles acting on phospholipase D‐linked metabotropic glutamate receptors (PLD‐mGluRs; Bewick et al. 2005 J. Physiol 562, 381‐). We have tested whether the SLVs in baroreceptor endings (Krauhs, 1979 J. Neurocytol. 8:401‐) show a similar mechanism that modulates both afferent discharge and reflex‐evoked responses. Baroreceptors were stimulated by ramp increases in arterial pressure while either afferent discharge or reflex changes in heart rate and sympathetic nerve activity were measured after superfusion of the aortic arch with either the PLD‐mGluR antagonist PCCG‐13 (20μM) or glutamate (10mM) in situ. PCCG‐13 decreased baroreceptor afferent activity by 35% (P<0.05) and glutamate increased discharge by 42% (P<0.05) relative to control levels. Cardiac baroreceptor reflex gain was was attenuated reversibly by PCCG‐13 by 51% from 2.8+0.4 bpm/mmHg (P<0.05). Baroreceptor reflex‐mediated sympathoinhibition was also depressed. Glutamate applied to the aortic arch mimicked a baroreflex response. These data indicate autogenic glutamate release from baroreceptor terminals regulate afferent discharge through PLD‐mGluRs to modulate reflex cardiac and sympathomotor responses. MRC funded research.

Development of Abnormal Gait Detection and Vibratory Stimulation System on Lower Limbs to Improve Gait Stability

The purpose of this study is to develop an abnormal gait detection algorithm and a vibratory stimulation system on a lower limb to improve gait stability and prevent falls. The system consists of a gait measurement module, an abnormal gait detection module, and a vibratory stimulation module. The gait measurement module measures the vertical acceleration of the ankle during walking using an accelerometer. The measured acceleration values are sent to a portable microcontroller, which controls vibratory stimulations to the ankles based on an algorithm that detects the peak acceleration values. If the acceleration peaks are found to occur irregularly, the abnormal gait detection algorithm activates the vibratory stimulation module. To determine the effect of vibratory stimulations under dynamic condition, this study investigated the contribution of ankle muscle proprioception on the control of dynamic stability and lower limb kinematics while walking using vibratory stimulation to alter the muscle spindle output of individuals' left lower limb. Vibrators were attached to the left ankle joint (tibialis anterior, triceps surae). Participants were required to walk along a travel path and step over an obstacle placed in their way. There were four task conditions; an obstacle (10%, 20%, and 30% of the participants' height) was positioned at the midpoint of the walkway, or the participants' walking path remained clear. For each obstacle condition, participants experienced either no vibration, or vibration of the tibialis anterior muscle and the triceps surae muscle of the left lower limb. Vibration began upon detection of an abnormal gait and continued for one second. Vibrating the ankle muscles of the left lower limb while stepping over an obstacle resulted in significant changes in COM behavior on both the anterior/posterior (A/P) and medial/lateral (M/L) planes. The results provide strong evidence that the primary endings of the ankle muscle spindles play a significant role in the control of posture and balance during the swing phase of locomotion by providing information on the movement of the body's COM with respect to the support foot.

A muscle spindle model and study the effects of static and dynamic γ stimulations on primary and secondary ending outputs

A linear lumped-parameter mechanical model of the muscle spindle is presented. It is shown that the model simulation exhibits the spindle behavior in most aspects of transient ramp-stretch performance. The requirements that such a model places on the mechanisms of fusimotor control are discussed. Then the efficacy of static γ and dynamic γ stimulation on primary ending output and secondary ending output is studied. The results of simulations show that primary ending of muscle spindle is affected either by static and dynamic stimulation and Secondary ending of muscle spindle is affected only by static fiber stimulation. The bias of primary ending output is increased by an increase in static γ stimulation. The Ramp of primary ending response is increased by an increase in dynamic γ stimulation. An increase in static γ stimulation in secondary ending of muscle spindle increases the dc level of secondary ending output so the bias of output is increased too.

Visualizing mechanosensory endings of TrkC‐expressing neurons in HS3ST‐2‐hPLAP mice

Somatosensory neurons are classified into three main types according to their modalities: nociceptive, thermal, and mechanosensory. Within each modality group, neurons can be further divided into morphologically and functionally distinct subclasses. Here we show that heparan sulfate D-glucosaminyl 3-O-sulfotransferase 2 (HS3ST-2) is a marker for specific subsets of TrkC-expressing cutaneous low-threshold mechanosensory and proprioceptive mechanosensory neurons. Two-color in situ analysis revealed that almost all HS3ST-2 signals colocalized with TrkC but not with TrkA or TrkB mRNA. To visualize the morphological subtypes of HS3ST-2/TrkC-expressing neurons, we generated a HS3ST-2-hPLAP knock-in mouse line, in which HS3ST-2-expressing neurons and their projections are labeled by human placental alkaline phosphatase (hPLAP). AP staining in these mice demonstrated that sensory endings of muscle spindles and Golgi tendon organs as well as the cutaneous mechanosensory Merkel and longitudinal lanceolate endings in the whiskers are strongly positive for hPLAP activity. In contrast, no nociceptive endings are labeled. In the glabrous and hairy skin, rare Merkel endings and transverse lanceolate endings are weakly stained. During development, each type of nerve endings forms at different time point. Muscle innervations differentiate first, followed by formation of cutaneous sensory endings. Our results revealed the subtype identities of TrkC-positive mechanosensory neurons and demonstrated the usefulness of HS3ST-2 as a genetic marker for these subclasses of neurons.

Local subcutaneous and muscle pain impairs detection of passive movements at the human thumb

Activity in both muscle spindle endings and cutaneous stretch receptors contributes to the sensation of joint movement. The present experiments assessed whether muscle pain and subcutaneous pain distort proprioception in humans. The ability to detect the direction of passive movements at the interphalangeal joint of the thumb was measured when pain was induced experimentally in four sites: the flexor pollicis longus (FPL), the subcutaneous tissue overlying this muscle, the flexor carpi radialis (FCR) muscle and the subcutaneous tissue distal to the metacarpophalangeal joint of thumb. Tests were conducted when pain was at a similar subjective intensity. There was no significant difference in the ability to detect flexion or extension under any painful or non-painful condition. The detection of movement was significantly impaired when pain was induced in the FPL muscle, but pain in the FCR, a nearby muscle that does not act on the thumb, had no effect. Subcutaneous pain also significantly impaired movement detection when initiated in skin overlying the thumb, but not in skin overlying the FPL muscle in the forearm. These findings suggest that while both muscle and skin pain can disturb the detection of the direction of movement, the impairment is site-specific and involves regions and tissues that have a proprioceptive role at the joint. Also, pain induced in FPL did not significantly increase the perceived size of the thumb. Proprioceptive mechanisms signalling perceived body size are less disturbed by a relevant muscle nociceptive input than those subserving movement detection. The results highlight the complex relationship between nociceptive inputs and their influence on proprioception and motor control.

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.

Effects of changes in pH on the afferent impulse activity of isolated cat muscle spindles

Muscle spindle activity has been shown to decrease in the sustained contracting muscle. The effect has been assumed to result from a declining fusimotor drive. Since accumulation of metabolites including H +, lactate and CO 2 might also affect the receptor in the fatiguing muscle, the impulse activity of muscle spindles isolated from the cat tenuissimus muscle was characterized under varying degrees of extracellular pH, thus excluding any effect on fusimotor activity, blood supply and extrafusal muscle fibers. The isolated receptor was exposed to bathing fluids of pH 6.4, 7.4 and 8.4, and afferent discharge activity was recorded from the spindle nerve. Both primary and secondary endings responded similarly to changes in pH. Resting discharge frequency usually decreased with decreasing pH and increased with increasing pH. A sudden break-off in activity was observed with about 40% of primary endings and about 30% of secondary endings at pH 6.4. Experiments with slow stretch stimulation indicated that this effect was caused by a rising threshold of firing at the encoder site of the endings. With brief ramp-and-hold stretches, we tested the effects of changes in pH on the dynamic and static sensitivity of primary and secondary endings. When pH was reduced from 7.4 to 6.4, the initial burst activity at the beginning of the ramp phase increased in primary and secondary endings and the dynamic response increased in secondary endings, demonstrating that the dynamic properties of muscle spindle endings were usually augmented in the acidic milieu. The static properties rose as well because the static index of both types of ending increased significantly. By contrast, dynamic and static properties of both primary and secondary endings decreased significantly, when pH was increased from 7.4 to 8.4. The amplitude of tension that was measured during the passive stretch stimuli very slightly decreased in the acidic solution and very slightly increased in the alkaline solution. The decrease in the resting discharge activity at low pH supports those previous observations, which demonstrate a reduced peripheral input from muscle spindle afferents to the spinal motor nuclei during fatigue in the isometric contracting muscle. The present finding indicates that an attenuated afferent discharge is not only caused by a decreasing central activation of γ-motorneurons, but may additionally be supported by a direct effect of protons on the muscle receptor itself. The accompanying augmentation of stretch sensitivity is suggested to correspond to the well-known increase in physiological tremor during exhaustive exercise.

Role of Occlusal Vertical Dimension in Spindle Function

Several studies have suggested the jaw-muscle spindle as the receptor responsible for regulating and maintaining the occlusal vertical dimension (OVD). However, to challenge this assumption, we hypothesized that long-term changes in OVD could affect the sensory inputs from jaw-muscle spindles. In this study, we investigated changes in masseter muscle spindle function under an increased OVD (iOVD) condition. Responses of primary and secondary endings of masseter muscle spindles to cyclic sinusoidal stretches were investigated. Twenty barbiturate-anesthetized female Wistar rats were divided into control and iOVD groups. Rats in the iOVD group received a 2.0-mm composite resin build-up to the maxillary molars. After iOVD, masseter muscle spindle sensitivity gradually decreased. Primary and secondary spindle endings were affected differently. We conclude that iOVD caused reduction in masseter muscle spindle sensitivity. This result suggests that peripheral sensory plasticity may occur following changes in OVD. Such changes may provide a basis for physiological adaptation to clinical occlusal adjustments.

Stochastic resonance in muscle receptors.

Noise is generally considered to have deleterious effects on the sensitivity of a signal detection system. There are, however, several mechanisms whereby the addition of noise to the input of a system can in fact improve sensitivity. One such mechanism is stochastic resonance. Although first proposed in 1981, conclusive experimental evidence for "fully tuneable stochastic resonance" in biological systems has not previously been reported. Evidence of fully tuneable stochastic resonance in the response of afferents from Golgi tendon organs and the primary and secondary endings of muscle spindles to imposed muscle length changes is presented.

Histochemical study of the sensory endings of muscle spindles in rat longissimus muscles

Most studies concerning the structure and function of muscle spindles have utilized the hind limbs of experimental animals. However, little is known about muscle spindles of the back muscles. The purpose of this study was to investigate the sensory innervation of muscle spindles of the paravertebral muscle in the rat. The subjects were 10 normal male rats. The longissimus muscles were isolated and frozen in cooled isopentane (-160 degrees C), and serial transverse sections were made with a cryostat. Histochemical preparations were then made using nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) stain and modified Gomori-trichrome stain. The muscle spindles in each segment were identified microscopically by observing the equatorial and polar regions. NADH-TR staining was employed to distinguish nuclear bag1, nuclear bag2, and nuclear chain intrafusal muscle fibers. A total of 20 spindle poles were surveyed. The mean polar length of intrafusal fibers as well as that of each region (A, B, and C) were measured. NADH-TR staining also demonstrated the terminal sites of sensory fibers along intrafusal fibers. All spindle poles surveyed were innervated by secondary sensory fibers in addition to primary sensory fibers. Eight spindle poles were intermediate type muscle spindles that were innervated by one primary sensory fiber and one secondary sensory fiber. Twelve spindle poles were complex type muscle spindles that were innervated by one primary sensory fiber and multiple secondary sensory fibers. The mean length of the A region was 223.1+/-37.9 microm (n=8) for intermediate type spindles and 493.8+/-157.0 microm (n=12) for complex type spindles. The length of the A region was significantly longer in the complex type spindles than in the intermediate type spindles (p<0.001). The results suggest that the innervations of secondary sensory fibers were well developed in the longissimus muscle spindles in the rat. The morphological features of muscle spindles of the longissimus muscle may represent the structural basis for qualitatively different afferent discharges that relate to the characteristic types of locomotion served by paravertebral muscles.

Static gamma-motoneurones couple group Ia and II afferents of single muscle spindles in anaesthetised and decerebrate cats.

Ideas about the functions of static gamma-motoneurones are based on the responses of primary and secondary endings to electrical stimulation of single static gamma-axons, usually at high frequencies. We compared these effects with the actions of spontaneously active gamma-motoneurones. In anaesthetised cats, afferents and efferents were recorded in intramuscular nerve branches to single muscle spindles. The occurrence of gamma-spikes, identified by a spike shape recognition system, was linked to video-taped contractions of type-identified intrafusal fibres in the dissected muscle spindles. When some static gamma-motoneurones were active at low frequency (< 15 Hz) they coupled the firing of group Ia and II afferents. Activity of other static gamma-motoneurones which tensed the intrafusal fibres appeared to enhance this effect. Under these conditions the secondary ending responded at shorter latency than the primary ending. In another series of experiments on decerebrate cats, responses of primary and secondary endings of single muscle spindles to activation of gamma-motoneurones by natural stimuli were compared with their responses to electrical stimulation of single gamma-axons supplying the same spindle. Electrical stimulation mimicked the natural actions of gamma-motoneurones on either the primary or the secondary ending, but not on both together. However, gamma-activity evoked by natural stimuli coupled the firing of afferents with the muscle at constant length, and also when it was stretched. Analysis showed that the timing and tightness of this coupling determined the degree of summation of excitatory postsynaptic potentials (EPSPs) evoked by each afferent in alpha-motoneurones and interneurones contacted by terminals of both endings, and thus the degree of facilitation of reflex actions of group II afferents.

Growth-associated protein-43 immunohistochemical and ultrastructural changes in jaw muscle spindles of the rat following loss of occlusion

The effects of complete loss of occlusion on the structural and functional status of these muscle spindles were investigated by immunohistochemistry either for protein gene product 9.5 (PGP 9.5) or growth-associated protein-43 (GAP-43) by light and electron microscopy. All the upper molars of 4-week-old Wistar rats were extracted and the erupted portions of the upper and lower incisors of the sarne animals were cut-off at the level of the interdental papilla every other day. In a control group, iminunoreactivity for GAP-43 was positive in the developing annulospiral endings of 2-week-old rats, but was not detected in any of the muscle spindles after 3 weeks of age. At 4 weeks of age, the PGP 9.5 immunostained spindles had well-differentiated annulospiral endings. Ultrastructurally, these afferent endings showed lenticular or circular profiles in cross-sections, and were differentially indented into the intrafusal-fibres. The inner surfaces of the terminals formed rather smooth myoneural junctions, while the outer surfaces were covered only by basal lamina continuous with that of the underlying intrafusal muscle fibres. After the experimental elimination of occlusal contact, GAP-43 immunoreactivity reappeared in some nerve endings of muscle spindles by 3 days, and persisted for at least 28 days. During this period, the afferent-terminals exhibited various fine structural abnormalities such as irregular outlines and invaginated neuromuscular interfaces. Some sensory-terminal (ST) profiles were completely engulfed by intrafusal-fibres. However, GAP-43 expression and ultrastructural alterations became undetectable within a week of the end of incisal cutting and the recovery of incisal-contact. These data indicate that remodelling of nerve terminals in muscle spindles, as assessed by GAP-43 expression and ultrastructural changes, occurs soon after a loss of occlusion, and ceases if incisal-contact is restored. It is concluded that possible changes in jaw muscle function, as well as a sudden loss of proprioceptive sensory input from the periodontal mechanoreceptors of molars and incisors, induce the structural reorganisation of nerve terminations in jaw muscle spindles that is associated with the appearance and disappearance of GAP-43 immunoreactivity.