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.

Tendon vibration is used extensively to assess the role of peripheral mechanoreceptors in motor control, specifically, the muscle spindles. Periodic tendon vibration is known to activate muscle spindles and induce a kinesthetic illusion that the vibrated muscle is longer than it actually is. Noisy tendon vibration has been used to assess the frequency characteristics of proprioceptive reflex pathways during standing; however, it is unknown if it induces the same kinesthetic illusions as periodic vibration. The purpose of the current study was to assess the effects of both periodic and noisy tendon vibration in a kinesthetic targeting task. Participants (N = 15) made wrist extension movements to a series of visual targets without vision of the limb, while their wrist flexors were either vibrated with periodic vibration (20, 40, 60, 80, and 100 Hz), or with noisy vibration which consisted of filtered white noise with power between ~ 20 and 100 Hz. Overall, our results indicate that both periodic and noisy vibration can induce robust targeting errors during a wrist targeting task. Specifically, the vibration resulted in an undershooting error when moving to the target. The findings from this study have important implications for the use of noisy tendon vibration to assess proprioceptive reflex pathways and should be considered when designing future studies using noisy vibration.

Proprioception, the sense of body position in space, has a critical role in the control of posture and movement. Aside from skin and joint receptors, the main sources of proprioceptive information in tetrapods are mechanoreceptive end organs in skeletal muscle: muscle spindles (MSs) and Golgi tendon organs (GTOs). The sensory neurons that innervate these receptors are divided into subtypes that detect discrete aspects of sensory information from muscles with different biomechanical functions. Despite the importance of proprioceptive neurons in motor control, the developmental mechanisms that control the acquisition of their distinct functional properties and positional identity are not yet clear. In this review, we discuss recent findings on the development of mouse proprioceptor subtypes and challenges in defining them at the molecular and functional level.