The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multiarticular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) coactivation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ coactivation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar, and cortical mechanisms.

Muscle spindles have unique anatomical characteristics that can be directly affected by the surrounding tissues under physiological and pathological conditions. Understanding their spatial distribution and density in different muscles is imperative to unravel the complexity of motor function. In the present study, the distribution and number/density of muscle spindles in human and animal muscles were reviewed. We identified 56 articles focusing on muscle spindle distribution; 13 articles focused on human muscles and 43 focused on animal muscles. The results demonstrate that spindles are located at the nerve entry points and along distributed vessels and they relate to the intramuscular connective tissue. Muscles\' deep layers and middle segments are the main topographic distribution areas. Eleven articles on humans and thirty-three articles on animals (totaling forty-four articles) focusing on muscle spindle quantity and density were identified. Hand and head muscles, such as the pronator teres/medial pterygoid muscle/masseter/flexor digitorum, were most commonly studied in the human studies. For animals, whole-body musculature was studied. The present study summarized the spindle quantity in 77 human and 189 animal muscles. We identified well-studied muscles and any as-yet unfound data. The current data fail to clarify the relationship between quantity/density and muscle characteristics. The intricate distribution of the muscle spindles and their density and quantity throughout the body present some unique patterns or correlations, according to the current data. However, it remains unclear whether muscles with fine motor control have more muscle spindles since the study standards are inconsistent and data on numerous muscles are missing. This study provides a comprehensive and exhaustive approach for clinicians and researchers to determine muscle spindle status.

Neuromuscular control of bionic arms has constantly improved over the past years, however, restoration of sensation remains elusive. Previous approaches to reestablish sensory feedback include tactile, electrical, and peripheral nerve stimulation, however, they cannot recreate natural, intuitive sensations. Here, we establish an experimental biological sensorimotor interface and demonstrate its potential use in neuroprosthetics. We transfer a mixed nerve to a skeletal muscle combined with glabrous dermal skin transplantation, thus forming a bi-directional communication unit in a rat model. Morphological analyses indicate reinnervation of the skin, mechanoreceptors, NMJs, and muscle spindles. Furthermore, sequential retrograde labeling reveals specific sensory reinnervation at the level of the dorsal root ganglia. Electrophysiological recordings show reproducible afferent signals upon tactile stimulation and tendon manipulation. The results demonstrate the possibility of surgically creating an interface for both decoding efferent motor control, as well as encoding afferent tactile and proprioceptive feedback, and may indicate the way forward regarding clinical translation of biological communication pathways for neuroprosthetic applications.

This study investigated whether abnormal peak inversion spontaneous potentials (PISPs) recorded at resting myofascial trigger points (MTrPs) stem from the discharge of muscle spindles. Forty-eight male Sprague-Dawley rats were randomly divided into six groups. Five groups underwent MTrP modeling intervention, whereas one group did not receive intervention and was duly designated as the blank control. After model construction, five rat models were randomly subjected to ramp-and-hold stretch tests, succinylcholine injection, eperisone hydrochloride injection, saline injection, and blank drug intervention. By contrast, the rats in the blank control group were subjected to ramp-and-hold stretch tests as a control. Frequencies and amplitudes of PISPs were recorded pre- and post-interventions and compared with those of the blank group. Stretch tests showed that the depolarization time and amplitude of PISPs ranged from 0.4 ms to 0.9 ms and from 80 uV to 140 μV, respectively. However, no PISPs were observed in the control rats. The frequency of PISPs in the ramp and hold phases and the first second after the hold phase was higher than that before stretching (p < 0.01). Succinylcholine and eperisone exerted excitatory and inhibitory effects on PISPs, respectively. In the group injected with 0.9% saline, no considerable differences of the PISPs were observed during the entire observation period. In conclusion, PISPs recorded at resting MTrPs are closely related to muscle spindles. The formation of MTrPs may be an important factor that regulate dysfunctional muscle spindles.

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The centre of the highest region of muscle spindle abundance (CHRMSA) in the intramuscular nerve-dense region has been suggested as the optimal target location for injecting botulinum toxin A to block muscle spasms. The anterior forearm muscles have a high incidence of spasticity. However, the CHRMSA in the intramuscular nerve-dense region of the forearm anterior muscle group has not been defined. This study aimed to accurately define the body surface position and the depth of CHRMSA in an intramuscular nerve-dense region of the anterior forearm muscles. Twenty-four adult cadavers (57.7 ± 11.5 years) were included in this study. The curved line close to the skin connecting the medial and lateral epicondyles of the humerus was designated as the horizontal reference line (H line), and the line connecting the medial epicondyle of the humerus and the ulnar styloid was defined as the longitudinal reference line (L line). Modified Sihler\'s staining, haematoxylin-eosin staining and computed tomography scanning were employed to determine the projection points (P and P\') of the CHRMSAs on the anterior and posterior surfaces of the forearm. The positions (PH and PL) of point P projected onto the H and L lines, and the depth of each CHRMSA, were determined using the Syngo system. The PH of the CHRMSA of the ulnar head of pronator teres, humeral head of pronator teres, flexor carpi radialis, palmaris longus, flexor carpi ulnaris, ulnar part of flexor digitorum superficialis, radial part of flexor digitorum superficialis, flexor pollicis longus, ulnar part of flexor digitorum profundus, radial portion of flexor digitorum profundus and pronator quadratus muscles were located at 42.48%, 45.52%, 41.20%, 19.70%, 7.77%, 25.65%, 47.42%, 53.47%, 12.28%, 38.41% and 51.68% of the H line, respectively; the PL were located at 18.38%, 12.54%, 28.83%, 13.43%, 17.65%, 32.76%, 57.32%, 64.12%, 20.05%, 45.94% and 88.71% of the L line, respectively; the puncture depths were located at 21.92%, 27.25%, 23.76%, 18.04%, 15.49%, 31.36%, 26.59%, 41.28%, 38.72%, 45.14% and 53.58% of the PP\' line, respectively. The percentage values are the means of individual values. We recommend that the body surface puncture position and depth of the CHRMSA are the preferred locations for the intramuscular injection of botulinum toxin A to block anterior forearm muscle spasms.

The primary motor cortex does not uniquely or directly produce alpha motoneurone (α-MN) drive to muscles during voluntary movement. Rather, α-MN drive emerges from the synthesis and competition among excitatory and inhibitory inputs from multiple descending tracts, spinal interneurons, sensory inputs, and proprioceptive afferents. One such fundamental input is velocity-dependent stretch reflexes in lengthening muscles, which should be inhibited to enable voluntary movement. It remains an open question, however, the extent to which unmodulated stretch reflexes disrupt voluntary movement, and whether and how they are inhibited in limbs with numerous multi-articular muscles. We used a computational model of a Rhesus Macaque arm to simulate movements with feedforward α-MN commands only, and with added velocity-dependent stretch reflex feedback. We found that velocity-dependent stretch reflex caused movement-specific, typically large and variable disruptions to arm movements. These disruptions were greatly reduced when modulating velocity-dependent stretch reflex feedback (i) as per the commonly proposed (but yet to be clarified) idealized alpha-gamma (α-γ) co-activation or (ii) an alternative α-MN collateral projection to homonymous γ-MNs. We conclude that such α-MN collaterals are a physiologically tenable, but previously unrecognized, propriospinal circuit in the mammalian fusimotor system. These collaterals could still collaborate with α-γ co-activation, and the few skeletofusimotor fibers (β-MNs) in mammals, to create a flexible fusimotor ecosystem to enable voluntary movement. By locally and automatically regulating the highly nonlinear neuro-musculo-skeletal mechanics of the limb, these collaterals could be a critical low-level enabler of learning, adaptation, and performance via higher-level brainstem, cerebellar and cortical mechanisms.

The goals of this review are to improve understanding of the aetiology of chronic muscle pain and identify new targets for treatments. Muscle pain is usually associated with trigger points in syndromes such as fibromyalgia and myofascial syndrome, and with small spots associated with spontaneous electrical activity that seems to emanate from fibers inside muscle spindles in EMG studies. These observations, added to the reports that large-diameter primary afferents, such as those innervating muscle spindles, become hyperexcitable and develop spontaneous ectopic firing in conditions leading to neuropathic pain, suggest that changes in excitability of these afferents might make an important contribution to the development of pathological pain. Here, we review evidence that the muscle spindle afferents (MSAs) of the jaw-closing muscles become hyperexcitable in a model of chronic orofacial myalgia. In these afferents, as in other large-diameter primary afferents in dorsal root ganglia, firing emerges from fast membrane potential oscillations that are supported by a persistent sodium current (INaP ) mediated by Na+ channels containing the α-subunit NaV 1.6. The current flowing through NaV 1.6 channels increases when the extracellular Ca2+ concentration decreases, and studies have shown that INaP -driven firing is increased by S100β, an astrocytic protein that chelates Ca2+ when released in the extracellular space. We review evidence of how astrocytes, which are known to be activated in pain conditions, might, through their regulation of extracellular Ca2+ , contribute to the generation of ectopic firing in MSAs. To explain how ectopic firing in MSAs might cause pain, we review evidence supporting the hypothesis that cross-talk between proprioceptive and nociceptive pathways might occur in the periphery, within the spindle capsule.

Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles makes these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle-tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp-and-hold and triangular stretches were analysed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor- and perturbation-like stretches as well as serial history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak and mean firing rates were not reduced and IFR was best-correlated with fascicle velocity. During ramp stretches, SEEs reduced the initial burst, dynamic and static responses of the spindle. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the serial history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length or velocity, or MTU force.

The sense of limb position is important, because it is believed to contribute to our sense of self-awareness. Muscle spindles, including both primary and secondary endings of spindles, are thought to be the principal position sensors. Passive spindles possess a property called thixotropy which allows their sensitivity to be manipulated. Here, thixotropic patterns of position errors have been studied with three commonly used methods of measurement of position sense. The patterns of errors have been used as indicators of the influence exerted by muscle spindles on a measured value of position sense. In two-arm matching, the blindfolded participant indicates the location of one arm by placement of the other. In one-arm pointing, the participant points to the perceived position of their other, hidden arm. In repositioning, one of the blindfolded participant\'s arms is placed at a chosen angle and they are asked to remember its position and then, after a delay, reproduce the position. The three methods were studied over the full range of elbow angles between 5° (elbow extension) and 125° (elbow flexion). Different outcomes were achieved with each method; in two-arm matching, position errors were symmetrical about zero and thixotropic influences were large, while in one-arm pointing, errors were biased towards extension. In repositioning, thixotropic effects were small. We conclude that each of the methods of measuring position sense comprises different mixes of peripheral and central influences. This will have to be taken into consideration by the clinician diagnosing disturbances in position sense.