Responses Of Spindle Afferents Research Articles

Vesicle-released glutamate is necessary to maintain muscle spindle afferent excitability but not dynamic sensitivity in adult mice.

Muscle spindle afferents are slowly adapting low threshold mechanoreceptors that report muscle length and movement information critical for motor control and proprioception. The rapidly adapting cation channel PIEZO2has been identified as necessary for muscle spindle afferent stretch sensitivity, although the properties of this channel suggest that additional molecular elements are necessary for mediating the complex slowly adapting response of muscle spindle afferents. We report that glutamate increases muscle spindle afferent static sensitivity in an ex vivo mouse muscle nerve preparation, although blocking glutamate packaging into vesicles by the sole vesicular glutamate transporter, VGLUT1, either pharmacologically or by transgenic knockout of one allele of VGLUT1 decreases muscle spindle afferent static but not dynamic sensitivity. Our results confirm that vesicle-released glutamate is an important contributor to maintained muscle spindle afferent excitability and may suggest a therapeutic target for normalizing muscle spindle afferent function. Muscle spindle afferents are slowly adapting low threshold mechanoreceptors that have both dynamic and static sensitivity to muscle stretch. The exact mechanism by which these neurons translate muscle movement into action potentials is not well understood, although the PIEZO2mechanically sensitive cation channel is essential for stretch sensitivity. PIEZO2 is rapidly adapting, suggesting the requirement for additional molecular elements to maintain firing during stretch. Spindle afferent sensory endings contain glutamate-filled synaptic-like vesicles that are released in a stretch- and calcium-dependent manner. Previous work has shown that glutamate can increase and a phospholipase-D coupled metabotropic glutamate antagonist can abolish firing during static stretch. Here, we test the hypothesis that vesicle-released glutamate is necessary for maintaining muscle spindle afferent excitability during static but not dynamic stretch. To test this hypothesis, we used a mouse muscle-nerve ex vivo preparation to measure identified muscle spindle afferent responses to stretch and vibration. In C57BL/6 adult mice, bath applied glutamate significantly increased the firing rate during the plateau phase of stretch but not during the dynamic phase of stretch. Blocking the packaging of glutamate into vesicles by the sole vesicular glutamate transporter, VGLUT1, either with xanthurenic acid or by using a transgenic mouse with only one copy of the VGLUT1 gene (VGLUT1+/- ), decreased muscle spindle afferent firing during sustained stretch but not during vibration. Our results suggest a model of mechanotransduction where calcium entering the PIEZO2 channel can cause the release of glutamate from synaptic-like vesicles, which then helps to maintain afferent depolarization and firing.

The Role of Glutamate in Maintaining Muscle Spindle Afferent Excitability in Adult Mice

Group Ia and II muscle spindle afferents are sensory neurons critical to detecting muscle movement and length, which is important in proprioception and motor control. Glutamate is released by synaptic‐like vesicles (SLVs) at muscle spindle afferent nerve endings and exogenous glutamate increases sensory neuron firing rate during stretch (Bewick, et al., 2005). However, the activity of individual muscle spindle afferents was not measured, allowing for the possibility that this increased firing also included other sensory neurons known to have glutamate receptors, like nociceptors. Here we test the hypothesis that glutamate increases the firing rate of individual muscle spindle afferents. We isolated the extensor digitorum longus muscle and the sciatic nerve from adult mice (8–12 wks old) and recorded the activity of individual muscle spindle afferents during exogenous glutamate treatment. The muscle‐nerve preparation was perfused in an oxygenated synthetic interstitial fluid tissue bath, an extracellular recording electrode was placed on the nerve to measure the activity of individual muscle spindle afferents, and a battery of 4s ramp‐and‐hold stretches were performed on the muscle. Glutamate addition led to a significant increase in muscle spindle afferent firing rate during stretch (1mM; n=12, 18.8%). We also decreased glutamate release by blocking the vesicular glutamate transporter 1 (VGLUT1) with the inhibitor xanthurenic acid (XA). We found a significant decrease in muscle spindle afferent firing rates (3mM; n=17, −39%), with 5 afferents exhibiting a complete absence of firing. However, we noticed heterogeneity in muscle spindle afferent responses to glutamate and XA treatment, with some afferents not responding at all to the drug treatments. To confirm our pharmacological findings, we obtained a transgenic mouse line lacking a single copy of vesicular glutamate transporter 1 (VGLUT1; B6.129X1‐Sic17a7tm1Edw/MmcD; Fremeau, 2004). We observed two muscle spindle afferents responding normally to stretch, while another two failed to sustain firing at the end of stretch, something that is only rarely seen in wild type animals. This heterogeneity may be due to differences in VGLUT1 protein levels in individual afferents. We are currently increasing our sample size, but our preliminary results support our hypothesis that glutamate is critical to maintaining muscle spindle afferent firing during maintained stretch. These studies will lead to a better understanding of how muscle spindle afferent stretch sensitivity is regulated.Support or Funding InformationThis work was supported by NIH SC3 GM127195 (KAW) and NIH R25 GM071381 (SO and NV).

Impaired muscle spindle function in murine models of muscular dystrophy.

Muscular dystrophy patients suffer from progressive degeneration of skeletal muscle fibres, sudden spontaneous falls, balance problems, as well as gait and posture abnormalities. Dystrophin- and dysferlin-deficient mice, models for different types of muscular dystrophy with different aetiology and molecular basis, were characterized to investigate if muscle spindle structure and function are impaired. The number and morphology of muscle spindles were unaltered in both dystrophic mouse lines but muscle spindle resting discharge and their responses to stretch were altered. In dystrophin-deficient muscle spindles, the expression of the paralogue utrophin was substantially upregulated, potentially compensating for the dystrophin deficiency. The results suggest that muscle spindles might contribute to the motor problems observed in patients with muscular dystrophy. Muscular dystrophies comprise a heterogeneous group of hereditary diseases characterized by progressive degeneration of extrafusal muscle fibres as well as unstable gait and frequent falls. To investigate if muscle spindle function is impaired, we analysed their number, morphology and function in wildtype mice and in murine model systems for two distinct types of muscular dystrophy with very different disease aetiology, i.e. dystrophin- and dysferlin-deficient mice. The total number and the overall structure of muscle spindles in soleus muscles of both dystrophic mouse mutants appeared unchanged. Immunohistochemical analyses of wildtype muscle spindles revealed a concentration of dystrophin and β-dystroglycan in intrafusal fibres outside the region of contact with the sensory neuron. While utrophin was absent from the central part of intrafusal fibres of wildtype mice, it was substantially upregulated in dystrophin-deficient mice. Single-unit extracellular recordings of sensory afferents from muscle spindles of the extensor digitorum longus muscle revealed that muscle spindles from both dystrophic mouse strains have an increased resting discharge and a higher action potential firing rate during sinusoidal vibrations, particularly at low frequencies. The response to ramp-and-hold stretches appeared unaltered compared to the respective wildtype mice. We observed no exacerbated functional changes in dystrophin and dysferlin double mutant mice compared to the single mutant animals. These results show alterations in muscle spindle afferent responses in both dystrophic mouse lines, which might cause an increased muscle tone, and might contribute to the unstable gait and frequent falls observed in patients with muscular dystrophy.

Acetylcholine receptors in the equatorial region of intrafusal muscle fibres modulate mouse muscle spindle sensitivity.

Acetylcholine receptors are aggregated in the central regions of intrafusal muscle fibres. Single unit muscle spindle afferent responses from isolated mouse extensor digitorum longus muscle were recorded in the absence of fusimotor input to ramp and hold stretches as well as to sinusoidal vibrations in the presence and absence of the acetylcholine receptor blockers d-tubocurarine andα-bungarotoxin. Proprioceptive afferent responses to both types of stretch were enhanced in the presence of either blocker. Blocking acetylcholine uptake and vesicular acetylcholine release by hemicholinium-3 also enhanced stretch-evoked responses. These results represent the first evidence that acetylcholine receptors negatively modulate muscle spindle responses to stretch. The data support the hypothesis that the sensory nerve terminal is able to release vesicles to fine-tune proprioceptive afferent sensitivity. Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of specialized skeletal muscle fibres, called intrafusal fibres, which are innervated in the central (equatorial) region by afferent sensory axons and in both polar regions by efferent γ-motoneurons. Previously it was shown that acetylcholine receptors (AChR) are concentrated in the equatorial region at the contact site between the sensory neuron and the intrafusal muscle fibre. To address the function of these AChRs, single unit sensory afferents were recorded from an isolated mouse extensor digitorum longus muscle in the absence of γ-motoneuron activity. Specifically, we investigated the responses of individual sensory neurons to ramp-and-hold stretches and sinusoidal vibrations before and after the addition of the competitive and non-competitive AChR blockers d-tubocurarine and α-bungarotoxin, respectively. The presence of either drug did not affect the resting action potential discharge frequency. However, the action potential frequencies in response to stretch were increased. In particular, frequencies of the dynamic peak and dynamic index to ramp-and-hold stretches were significantly higher in the presence of either drug. Treatment of muscle spindle afferents with the high-affinity choline transporter antagonist hemicholinium-3 similarly increased muscle spindle afferent firing frequencies during stretch. Moreover, the firing rate during sinusoidal vibration stimuli at low amplitudes was higher in the presence of α-bungarotoxin compared to control spindles also indicating an increased sensitivity to stretch. Collectively these data suggest a modulation of the muscle spindle afferent response to stretch by AChRs in the central region of intrafusal fibres possibly fine-tuning muscle spindle sensitivity.

Lipopolysaccharide-induced inflammation does not alter muscle spindle afferent mechanosensation or sensory integration in the spinal cord of adult mice.

Inflammation is known to alter nervous system function, but its effect on muscle spindle afferent mechanosensation and sensory integration in the spinal cord has not been well studied. We tested the hypothesis that systemic inflammation induced by an intraperitoneal injection of the endotoxin lipopolysaccharide (LPS; 7.5 × 105 endotoxin units/kg 18 h before experiment) would alter muscle spindle afferent mechanosensation and spinal cord excitability to Group Ia input in male and female adult C57Bl/6 mice. LPS injection caused a systemic immune response, evidenced by decreased white blood cell, monocyte, and lymphocyte concentrations in the blood, increased blood granulocyte concentration, and body weight loss. The immune response in both sexes was qualitatively similar. We used an in vitro muscle‐nerve preparation to assay muscle spindle afferent response to stretch and vibration. LPS injection did not significantly change the response to stretch or vibration, with the exception of small decreases in the ability to entrain to high‐frequency vibration in male mice. Similarly, LPS injection did not alter spinal cord excitability to Group Ia muscle spindle afferent input as measured by the Hoffman's reflex test in anesthetized mice (100 mg/kg ketamine, 10 mg/kg xylazine). Specifically, there were no changes in M or H wave latencies nor in the percentage of motor neurons excited by electrical afferent stimulation (Hmax/Mmax). Overall, we found no major alterations in muscle proprioceptor function or sensory integration following exposure to LPS at a dose and time course that causes changes in nociceptor function and central processing.

The Effects of Acute Lipopolysaccharide Induced Inflammation on Spinal Cord Excitability

Peripheral inflammation alters the excitability of dorsal horn interneurons and increases flexor reflex strength (Dubner & Ruda, 1992); however, its effect on the spinal stretch reflex is not well understood. The stretch reflex is a muscle contraction in response to muscle stretch. We hypothesize that the acute inflammation caused by an injection of lipopolysaccharide (LPS) will cause an increase in spinal cord excitability. To test this hypothesis, we measured Hoffman’s (H) reflex, the electric analog of the stretch reflex in adult mice receiving an injection of LPS (.5mg/kg) or saline (200μl). Adult male and female mice (C57Bl/6) were anesthetized; then, the sciatic nerve was exposed and stimulated at current strengths from H-wave threshold (T) to 8T (20 x 0.1 ms pulses at 0.1 Hz). Recording electrodes were placed in the foot. We measured the maximum M wave amplitude (Mmax), maximum H wave amplitude (Hmax) and latencies of both waves. We compared the ratio of the maximal H wave over the maximal M wave (Hmax/Mmax), which reports the percentage of motor neurons activated by electrical stimulation of Group Ia muscle sensory neurons. Increased spinal cord excitability would be reflected in a larger Hmax/Mmax. We found that LPS-induced inflammation does not alter the Hmax/Mmax. While we found no evidence of changes in spinal cord excitability, inflammation could be altering Group Ia muscle spindle afferent responses to stretch. Future studies will test whether stretch reflex strength is altered by inflammation.

Diet induced obesity alters muscle spindle afferent function in adult mice.

Populations with obesity are more likely to fall and exhibit balance instability. The reason for this is likely multifactorial, but there is some evidence that sensory function is impaired during obesity. We tested the hypothesis that muscle proprioceptor function is compromised in a mouse model of diet induced obesity. An in vitro muscle-nerve preparation was used to record muscle spindle afferent responses to physiological stretch and sinusoidal vibration. We compared the responses of C57/Bl6 male and female mice on a control diet (10% kcal fat) with those eating a high fat diet (HFD; 60% kcal fat) for 10 weeks (final age 14–15 weeks old). Following HFD feeding, adult mice of both sexes exhibited decreased muscle spindle afferent responses to muscle movement. Muscle spindle afferent firing rates during the plateau phase of stretch were significantly lower in both male and female HFD animals as were two measures of dynamic sensitivity (dynamic peak and dynamic index). Muscle spindle afferents in male mice on a HFD were also significantly less likely to entrain to vibration. Due to the importance of muscle spindle afferents to proprioception and motor control, decreased muscle spindle afferent responsiveness may contribute to balance instability during obesity.

Fos immunoreactivity in the intermediolateral nucleus induced by tendon vibration of the m. triceps surae in rats pretreated with a nitric oxide blocker or precursor

We investigated neuronal activation of the rat intermediolateral (IML) nucleus of the thoracolumbar spinal cord, initiated by Achilles tendon vibration, after intramuscular (m. triceps surae) administration of 7‑nitroindazole (7‑NI) or L‑arginine (LA). The spindle afferent response to vibratory stimuli induced a distinct bilateral increase in the activation of c‑Fos immunoreactivity in the spinal neurons in three groups of rats (tendon‑vibrated, tendon‑vibrated + 7‑NI and tendon‑vibrated + LA). The T5/T13 segments in tendon‑vibrated +7‑NI animals showed the highest increase of Fos‑immunoreactive neurons. This increase was two times higher than that in tendon only‑vibrated control rats and endon‑vibrated + LA animals. The highest mean number of labelled neurons were observed in the IML nucleus and in layers 4 and 7 of the T5-L3 segments in tendon‑vibrated and tendon‑vibrated + 7‑NI animals, and in the IML nucleus and layer 4 in tendon‑vibrated + LA rats. The highest mean number of activated neurons was found ipsilaterally in the IML nucleus of the T5/T13 segment. These results indicate that decreased nitric oxide release after injection of 7‑NI was accompanied by a potentiation of the early c‑fos gene expression induced by muscle proprioceptive activity within the thoracolumbar region of the rat spinal cord. Thus, enhanced c‑Fos immunoreactivity in the IML nucleus indicated that the sympathetic nervous system can exert a direct influence on the muscle spindles.

Enhanced Muscle Afferent Signals during Motor Learning in Humans

Much has been revealed concerning human motor learning at the behavioral level [1, 2], but less is known about changes in the involved neural circuits and signals. By examining muscle spindle responses during a classic visuomotor adaptation task [3-6] performed by fully alert humans, I found substantial modulation of sensory afferent signals as a functionof adaptation state. Specifically, spindle control was independent of concurrent muscle activity butwas specific to movement direction (representing muscle lengthening versus shortening) and to different stages of learning. Increased spindle afferent responses to muscle stretch occurring early during learning reflected individual error size and were negatively related to subsequent antagonist activity (i.e., 60-80ms thereafter). Relative increases in tonic afferent output early during learning were predictive of the subjects' adaptation rate. I also found that independent spindle control during sensory realignment (the "washout" stage) induced afferent signal "linearization" with respect to muscle length (i.e., signals were more tuned to hand position). The results demonstrate for the first time that motor learning also involves independent and state-related modulation of sensory mechanoreceptor signals. The current findings suggest that adaptive motor performance also relies on the independent control of sensors, not just of muscles. I propose that the "γ" motor system innervating spindles acts to facilitate the acquisition and extraction of task-relevant information at the early stages of sensorimotor adaptation. This designates a more active and targeted role for the human proprioceptive system during motor learning.

Human muscle spindle sensitivity reflects the balance of activity between antagonistic muscles.

Muscle spindles are commonly considered as stretch receptors encoding movement, but the functional consequence of their efferent control has remained unclear. The "α-γ coactivation" hypothesis states that activity in a muscle is positively related to the output of its spindle afferents. However, in addition to the above, possible reciprocal inhibition of spindle controllers entails a negative relationship between contractile activity in one muscle and spindle afferent output from its antagonist. By recording spindle afferent responses from alert humans using microneurography, I show that spindle output does reflect antagonistic muscle balance. Specifically, regardless of identical kinematic profiles across active finger movements, stretch of the loaded antagonist muscle (i.e., extensor) was accompanied by increased afferent firing rates from this muscle compared with the baseline case of no constant external load. In contrast, spindle firing rates from the stretching antagonist were lowest when the agonist muscle powering movement (i.e., flexor) acted against an additional resistive load. Stepwise regressions confirmed that instantaneous velocity, extensor, and flexor muscle activity had a significant effect on spindle afferent responses, with flexor activity having a negative effect. Therefore, the results indicate that, as consequence of their efferent control, spindle sensitivity (gain) to muscle stretch reflects the balance of activity between antagonistic muscles rather than only the activity of the spindle-bearing muscle.

An <em>In Vitro</em> Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice.

An in vitro adult mouse muscle-nerve preparation for studying the firing properties of muscle afferents.

Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice.

Consideration of mechanisms of muscular rigidity in Parkinson's disease

Background: Rigidity is one of the cardinal symptoms in Parkinson's disease. Based on the findings of microneurography, Burke D et al. (1977) suggested that, in Parkinson patients, the spindle afferent responses look like those of normal subjects who are not fully relaxed and in whom there is a co-activation of the skeletomotor and fusimotor activity. In previous paper (J Physiol, 1998), we showed the existence of dynamic and static fusimotor actions on the human muscle spindle during voluntary contraction.

Attenuation of autonomic reflexes by A803467 may not be solely caused by blockade of NaV 1.8 channels

In decerebrated rats, we determined the dose of A803467, a NaV 1.8 antagonist, needed to attenuate the reflex pressor responses to femoral arterial injections of lactic acid (24mM; ~0.1ml) and capsaicin (0.1μg), agents which stimulate thin fiber afferents having NaV 1.8 channels. We also determined whether the dose of A803467 needed to attenuate these reflex responses affected the responses of muscle spindle afferents to tendon stretch and succinylcholine (200μg). Spindle afferents are not supplied with NaV 1.8 channels, and consequently their responses to these stimuli should not be influenced by A803467. Pressor responses to lactic acid and capsaicin were not altered by 500μg of A803467 (n=6). A803467 in a dose of 1mg, however, significantly reduced (p<0.05; n=12) the pressor responses to lactic acid (23±5 to 7±3ΔmmHg) and capsaicin (47±5 to 31±5ΔmmHg). Surprisingly, we also found that 1mg of A803467 reduced the responses of 10 spindle afferents to succinylcholine (34±11 to 4±3Δimp/s; p<0.05) and stretch (83±17 to 0.4±1Δimp/s; p<0.05). We conclude that A803467 reduces the reflex response to lactic acid and capsaicin; however, it may be working on multiple channels, including NaV 1.8, other NaVs as well as voltage-gated calcium channels.

Characterization of Muscle Spindle Afferents in the Adult Mouse Using an In Vitro Muscle-Nerve Preparation

We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli. Responses were measured at both room (24°C) and muscle body temperature (34°C). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length [Lo]). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10–100 Hz) and amplitude ranges tested (5–100 µm). Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. Cooling the muscle to 24°C decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. The ramp component of stretch generated dynamic firing responses. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.

Inducing Any Virtual Two-Dimensional Movement in Humans by Applying Muscle Tendon Vibration

In humans, tendon vibration evokes illusory sensation of movement. We developed a model mimicking the muscle afferent patterns corresponding to any two-dimensional movement and checked its validity by inducing writing illusory movements through specific sets of muscle vibrators. Three kinds of illusory movements were compared. The first was induced by vibration patterns copying the responses of muscle spindle afferents previously recorded by microneurography during imposed ankle movements. The two others were generated by the model. Sixteen different vibratory patterns were applied to 20 motionless volunteers in the absence of vision. After each vibration sequence, the participants were asked to name the corresponding graphic symbol and then to reproduce the illusory movement perceived. Results showed that the afferent patterns generated by the model were very similar to those recorded microneurographically during actual ankle movements (r=0.82). The model was also very efficient for generating afferent response patterns at the wrist level, if the preferred sensory directions of the wrist muscle groups were first specified. Using recorded and modeled proprioceptive patterns to pilot sets of vibrators placed at the ankle or wrist levels evoked similar illusory movements, which were correctly identified by the participants in three quarters of the trials. Our proprioceptive model, based on neurosensory data recorded in behaving humans, should then be a useful tool in fields of research such as sensorimotor learning, rehabilitation, and virtual reality.

Fusimotor Drive May Adjust Muscle Spindle Feedback to Task Requirements in Humans

The aim of the present study was to investigate whether the fusimotor control of muscle spindle sensitivity may depend on the movement parameter the task is focused on, either the velocity or the final position reached. The unitary activities of 18 muscle spindle afferents were recorded by microneurography at the common peroneal nerve. We compared in two situations the responses of muscle spindle afferents to ankle movements imposed while the subject was instructed not to pay attention to or to pay attention to the movement, both in the absence of visual cues. In the two situations, three ramp-and-hold movements were imposed in random order. In one situation, the three movements differed by their velocity and in the other by the final position reached. The task consisted in ranking the three movements according to the parameter under consideration (for example, slow, fast, and medium). The results showed that paying attention to movement velocity gave rise to a significant increase in the dynamic and static responses of muscle afferents. In contrast, focusing attention on the final position reached made the muscle spindle feedback better discriminate the different positions and depressed its capacity to discriminate movement velocities. Changes are interpreted as reflecting dynamic and static gamma activation, respectively. The present results support the view that the fusimotor drive depends on the parameter the task is focused on, so that the muscle afferent feedback is adjusted to the task requirements.

The influence of pain on masseter spindle afferent discharge

Muscle spindles provide proprioceptive feedback supporting normal patterns of motor activity and kinesthetic sensibility. During mastication, jaw muscle spindles play an important role in monitoring and regulating the chewing cycle and the bite forces generated during mastication. Both acute and chronic orofacial pain disorders are associated with changes in proprioceptive feedback and motor function. Experimental jaw muscle pain also alters the normal response of masseter spindle afferents to ramp and hold jaw movements. 1 It has been proposed that altered motor function and proprioceptive input results from group III muscle afferent modulation of the fusimotor system which alters spindle afferent sensitivity in limb muscles. 2 The response to nociceptive stimuli may enhance or reduce the response of spindle afferents to proprioceptive stimuli. Several experimental observations suggesting the possibility that a similar mechanism also functions in jaw muscles are presented in this report. First, evidence is provided to show that nociceptive stimulation of the masseter muscle primarily influences the amplitude sensitivity of spindle afferents with relatively little effect on the dynamic sensitivity. 3 Second, reversible inactivation of the caudal trigeminal nuclei attenuates the nociceptive modulation of spindle afferents. Finally, functionally identified gamma-motoneurons in the trigeminal motor nucleus are modulated by intramuscular injection with algesic substances. Taken together, these results suggest that pain-induced modulation of spindle afferent responses are mediated by small diameter muscle afferents and that this modulation is dependent, in part, on the relay of muscle nociceptive information from trigeminal subnucleus caudalis onto trigeminal gamma-motoneurons. The implication of these results will be considered in light of current theories on the relationship between jaw muscle pain and oral motor function.

The effect of experimental muscle pain on the amplitude and velocity sensitivity of jaw closing muscle spindle afferents

The effect of experimental muscle pain on the amplitude and velocity sensitivity of muscle spindle primary afferent neurons in the trigeminal mesencephalic nucleus (Vmes) was examined. Extracellular recordings were made from 45 neurons designated as spindle primary- or secondary-like on the basis of their response to ramp-and-hold jaw movements. Velocity sensitivity was assessed in spindle primary-like afferents by calculating the mean dynamic index of each unit in response to three different velocities of jaw opening before and after intramuscular injection with hypertonic saline (HS, 5%, 100 μl). The amplitude sensitivity of all jaw muscle spindle afferents was assessed by calculating the mean firing rate of each unit in response to three different amplitudes of jaw openings during both the open and hold phases of the movement and with best-fit lines obtained, using linear regression analysis, before and after HS injection. The variance of the two regression lines obtained for each unit before and after the injection was compared using the coincidence test, and changes in intercept and slope were determined. Seventy-five percent of the primary-like units and 80% of the secondary-like units presented with changes in static behavior after HS injection. Thirty-six percent of the primary-like units showed changes in dynamic behavior. Injection of isotonic saline (control) did not alter the responses of the spindle afferent to jaw opening. Thus, our results demonstrate that the predominant effect of noxious stimulation was a shift in the amplitude sensitivity of both spindle primary-like and secondary-like afferents and, to a lesser extent, the velocity sensitivity of the spindle primary-like unit. In accordance with earlier studies in the cat hindlimb and neck muscles, these results suggest that the activation of masseter muscle nociceptor alters spindle afferent responses to stretch acting primarily through static gamma motor neurons.

Movement reduces the dynamic response of muscle spindle afferents and motoneuron synaptic potentials in rat.

Among the mechanisms that may result in modulation of the stretch reflex by the recent history of muscle contraction is the history dependence observed under some conditions in the response properties of muscle spindles. The present study was designed to test one report that in successive trials of muscle stretch-release, spindle afferent firing during stretch, i.e., the dynamic response shows no history dependence beyond the initial burst of firing at stretch onset. Firing responses of spindle afferents were recorded during sets of three consecutive trials of triangular stretch-release applied to triceps surae muscles in barbiturate-anesthetized rats. All 69 spindle afferents fired more action potentials (spikes) during the dynamic response of the first trial, excluding the initial burst, than in the following two trials. The reduced dynamic response (RDR) was nearly complete after trial 1 and amounted to an average of approximately 12 fewer spikes (16 pps slower firing rate) in trial 3 than in trial 1. RDR was sensitive to the interval between stretch sets but independent of stretch velocity (4-32 mm/s). RDR was reflected in the synaptic potentials recorded intracellularly from 16 triceps surae alpha-motoneurons: depolarization during muscle stretch was appreciably reduced after trial 1. These findings demonstrate history dependence of spindle afferent responses that extends throughout the dynamic response in successive muscle stretches and that is synaptically transmitted to motoneurons with the probable effect, unless otherwise compensated, of modulating the stretch reflex.