Task-driven neural network models predict neural dynamics of proprioception.

Proprioception tells the brain the state of the body based on distributed sensory neurons. Yet, the principles that govern proprioceptive processing are poorly understood. Here, we employ a task-driven modeling approach to investigate the neural code of proprioceptive neurons in cuneate nucleus (CN) and somatosensory cortex area 2 (S1). We simulated muscle spindle signals through musculoskeletal modeling and generated a large-scale movement repertoire to train neural networks based on 16 hypotheses, each representing different computational goals. We found that the emerging, task-optimized internal representations generalize from synthetic data to predict neural dynamics in CN and S1 of primates. Computational tasks that aim to predict the limb position and velocity were the best at predicting the neural activity in both areas. Since task optimization develops representations that better predict neural activity during active than passive movements, we postulate that neural activity in the CN and S1 is top-down modulated during goal-directed movements.

The Form and Function of PIEZO2.

Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) and is essential for a wide variety of processes, including our sense of touch on the skin. How touch is detected and transduced at the molecular level has proved to be one of the great mysteries of sensory biology. A major breakthrough occurred in 2010 with the discovery of a family of mechanically gated ion channels that were coined PIEZOs. The last 10 years of investigation have provided a wealth of information about the functional roles and mechanisms of these molecules. Here we focus on PIEZO2, one of the two PIEZO proteins found in humans and other mammals. We review how work at the molecular, cellular, and systems levels over the past decade has transformed our understanding of touch and led to unexpected insights into other types of mechanosensation beyond the skin.

Physiology and Pathophysiology of Mechanically Activated PIEZO Channels.

Nearly all structures in our body experience mechanical forces. At a molecular scale, these forces are detected by ion channels that function as mechanotransducers converting physical forces into electrochemical responses. Here we focus on PIEZOs, a family of mechanically activated ion channels comprising PIEZO1 and PIEZO2. The significance of these channels is highlighted by their roles in touch and pain sensation as well as in cardiovascular and respiratory physiology, among others. Moreover, mutations in PIEZOs cause somatosensory, proprioceptive, and blood disorders. The goal here is to present the diverse physiology and pathophysiology of these unique channels, discuss ongoing research and critical gaps in the field, and explore the pharmaceutical interest in targeting PIEZOs for therapeutic development.

Feeling force: physical and physiological principles enabling sensory mechanotransduction.

Organisms as diverse as microbes, roundworms, insects, and mammals detect and respond to applied force. In animals, this ability depends on ionotropic force receptors, known as mechanoelectrical transduction (MeT) channels, that are expressed by specialized mechanoreceptor cells embedded in diverse tissues and distributed throughout the body. These cells mediate hearing, touch, and proprioception and play a crucial role in regulating organ function. Here, we attempt to integrate knowledge about the architecture of mechanoreceptor cells and their sensory organs with principles of cell mechanics, and we consider how engulfing tissues contribute to mechanical filtering. We address progress in the quest to identify the proteins that form MeT channels and to understand how these channels are gated. For clarity and convenience, we focus on sensory mechanobiology in nematodes, fruit flies, and mice. These themes are emphasized: asymmetric responses to applied forces, which may reflect anisotropy of the structure and mechanics of sensory mechanoreceptor cells, and proteins that function as MeT channels, which appear to have emerged many times through evolution.

Deletion of a conserved genomic region associated with adolescent idiopathic scoliosis leads to vertebral rotation in mice.

Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, in which spinal curvature develops in adolescence, and 90% of patients are female. Scoliosis is a debilitating disease that often requires bracing or surgery in severe cases. AIS affects 2%-5.2% of the population; however, the biological origin of the disease remains poorly understood. In this study, we aimed to determine the function of a highly conserved genomic region previously linked to AIS using a mouse model generated by CRISPR-CAS9 gene editing to knockout this area of the genome to understand better its contribution to AIS, which we named AIS_CRMΔ. We also investigated the upstream factors that regulate the activity of this enhancer in vivo, whether the spatial expression of the LBX1 protein would change with the loss of AIS-CRM function, and whether any phenotype would arise after deletion of this region. We found a significant increase in mRNA expression in the developing neural tube at E10.5, and E12.5, for not only Lbx1 but also other neighboring genes. Adult knockout mice showed vertebral rotation and proprioceptive deficits, also observed in human AIS patients. In conclusion, our study sheds light on the elusive biological origins of AIS, by targeting and investigating a highly conserved genomic region linked to AIS in humans. These findings provide valuable insights into the function of the investigated region and contribute to our understanding of the underlying causes of this debilitating disease.

A proprioceptive feedback circuit drives Caenorhabditis elegans locomotor adaptation through dopamine signaling.

An animal adapts its motor behavior to navigate the external environment. This adaptation depends on proprioception, which provides feedback on an animal's body postures. How proprioception mechanisms interact with motor circuits and contribute to locomotor adaptation remains unclear. Here, we describe and characterize proprioception-mediated homeostatic control of undulatory movement in the roundworm Caenorhabditis elegans. We found that the worm responds to optogenetically or mechanically induced decreases in midbody bending amplitude by increasing its anterior amplitude. Conversely, it responds to increased midbody amplitude by decreasing the anterior amplitude. Using genetics, microfluidic and optogenetic perturbation response analyses, and optical neurophysiology, we elucidated the neural circuit underlying this compensatory postural response. The dopaminergic PDE neurons proprioceptively sense midbody bending and signal to AVK interneurons via the D2-like dopamine receptor DOP-3. The FMRFamide-like neuropeptide FLP-1, released by AVK, regulates SMB head motor neurons to modulate anterior bending. We propose that this homeostatic behavioral control optimizes locomotor efficiency. Our findings demonstrate a mechanism in which proprioception works with dopamine and neuropeptide signaling to mediate motor control, a motif that may be conserved in other animals.

Proprioceptive and Visual Feedback Responses in Macaques Exploit Goal Redundancy.

A common problem in motor control concerns how to generate patterns of muscle activity when there are redundant solutions to attain a behavioral goal. Optimal feedback control is a theory that has guided many behavioral studies exploring how the motor system incorporates task redundancy. This theory predicts that kinematic errors that deviate the limb should not be corrected if one can still attain the behavioral goal. Studies in humans demonstrate that the motor system can flexibly integrate visual and proprioceptive feedback of the limb with goal redundancy within 90 ms and 70 ms, respectively. Here, we show monkeys (Macaca mulatta) demonstrate similar abilities to exploit goal redundancy. We trained four male monkeys to reach for a goal that was either a narrow square or a wide, spatially redundant rectangle. Monkeys exhibited greater trial-by-trial variability when reaching to the wide goal consistent with exploiting goal redundancy. On random trials we jumped the visual feedback of the hand and found monkeys corrected for the jump when reaching to the narrow goal and largely ignored the jump when reaching for the wide goal. In a separate set of experiments, we applied mechanical loads to the arm of the monkey and found similar corrective responses based on goal shape. Muscle activity reflecting these different corrective responses were detected for the visual and mechanical perturbations starting at ∼90 and ∼70 ms, respectively. Thus, rapid motor responses in macaques can exploit goal redundancy similar to humans, creating a paradigm to study the neural basis of goal-directed motor action and motor redundancy.SIGNIFICANCE STATEMENT Moving in the world requires selecting from an infinite set of possible motor commands. Theories predict that motor commands are selected that exploit redundancies. Corrective responses in humans to either visual or proprioceptive disturbances of the limb can rapidly exploit redundant trajectories to a goal in <100 ms after a disturbance. However, uncovering the neural correlates generating these rapid motor corrections has been hampered by the absence of an animal model. We developed a behavioral paradigm in monkeys that incorporates redundancy in the form of the shape of the goal. Critically, monkeys exhibit corrective responses and timings similar to humans performing the same task. Our paradigm provides a model for investigating the neural correlates of sophisticated rapid motor corrections.

How we perceive the width of grasped objects: Insights into the central processes that govern proprioceptive judgements.

Low-level proprioceptive judgements involve a single frame of reference, whereas high-level proprioceptive judgements are made across different frames of reference. The present study systematically compared low-level (grasp → $\rightarrow$ grasp) and high-level (vision → $\rightarrow$ grasp, grasp → $\rightarrow$ vision) proprioceptive tasks, and quantified the consistency of grasp → $\rightarrow$ vision and possible reciprocal nature of related high-level proprioceptive tasks. Experiment 1 (n = 30) compared performance across vision → $\rightarrow$ grasp, a grasp → $\rightarrow$ vision and a grasp → $\rightarrow$ grasp tasks. Experiment 2 (n = 30) compared performance on the grasp → $\rightarrow$ vision task between hands and over time. Participants were accurate (mean absolute error 0.27 cm [0.20 to 0.34]; mean [95% CI]) and precise ( R 2 $R^2$ = 0.95 [0.93 to 0.96]) for grasp → $\rightarrow$ grasp judgements, with a strong correlation between outcomes (r = -0.85 [-0.93 to -0.70]). Accuracy and precision decreased in the two high-level tasks ( R 2 $R^2$ = 0.86 and 0.89; mean absolute error = 1.34 and 1.41 cm), with most participants overestimating perceived width for the vision → $\rightarrow$ grasp task and underestimating it for grasp → $\rightarrow$ vision task. There was minimal correlation between accuracy and precision for these two tasks. Converging evidence indicated performance was largely reciprocal (inverse) between the vision → $\rightarrow$ grasp and grasp → $\rightarrow$ vision tasks. Performance on the grasp → $\rightarrow$ vision task was consistent between dominant and non-dominant hands, and across repeated sessions a day or week apart. Overall, there are fundamental differences between low- and high-level proprioceptive judgements that reflect fundamental differences in the cortical processes that underpin these perceptions. Moreover, the central transformations that govern high-level proprioceptive judgements of grasp are personalised, stable and reciprocal for reciprocal tasks. KEY POINTS: Low-level proprioceptive judgements involve a single frame of reference (e.g. indicating the width of a grasped object by selecting from a series of objects of different width), whereas high-level proprioceptive judgements are made across different frames of reference (e.g. indicating the width of a grasped object by selecting from a series of visible lines of different length). We highlight fundamental differences in the precision and accuracy of low- and high-level proprioceptive judgements. We provide converging evidence that the neural transformations between frames of reference that govern high-level proprioceptive judgements of grasp are personalised, stable and reciprocal for reciprocal tasks. This stability is likely key to precise judgements and accurate predictions in high-level proprioception.

PIEZO ion channels: force sensors of the interoceptive nervous system.

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery of the mechanosensory PIEZO ion channels (Coste et al., 2010). The role of these mechanosensors within the interoceptive nervous system is the focus of this review. In defining the transduction molecules that govern mechanical interoception, we will have a better grasp of how these signals drive physiology.

Volitional muscle activation intensifies neuronal processing of proprioceptive afference in the primary sensorimotor cortex: an EEG study.

Proprioception refers to the ability to perceive the position and movement of body segments in space. The cortical aspects of the proprioceptive afference from the body can be investigated using corticokinematic coherence (CKC). CKC accurately quantifies the degree of coupling between cortical activity and limb kinematics, especially if precise proprioceptive stimulation of evoked movements is used. However, there is no evidence on how volitional muscle activation during proprioceptive stimulation affects CKC strength. Twenty-five healthy volunteers (28.8 ± 7 yr, 11 females) participated in the experiment, which included electroencephalographic (EEG), electromyographic (EMG), and kinematic recordings. Ankle-joint rotations (2-Hz) were elicited through a movement actuator in two conditions: passive condition with relaxed ankle and active condition with constant 5-Nm plantar flexion exerted during the stimulation. In total, 6 min of data were recorded per condition. CKC strength was defined as the maximum coherence value among all the EEG channels at the 2-Hz movement frequency for each condition separately. Both conditions resulted in significant CKC peaking at the Cz electrode over the foot area of the primary sensorimotor (SM1) cortex. Stronger CKC was found for the active (0.13 ± 0.14) than the passive (0.03 ± 0.04) condition (P < 0.01). The results indicated that volitional activation of the muscles intensifies the neuronal proprioceptive processing in the SM1 cortex. This finding could be explained both by peripheral sensitization of the ankle joint proprioceptors and central modulation of the neuronal proprioceptive processing at the spinal and cortical levels.NEW & NOTEWORTHY The current study is the first to investigate the effect of volitional muscle activation on CKC-based assessment of cortical proprioception of the ankle joint. Results show that the motor efference intensifies the neuronal processing of proprioceptive afference of the ankle joint. This is a significant finding as it may extend the use of CKC method during active tasks to further evaluate the motor efference-proprioceptive afference relationship and the related adaptations to exercise, rehabilitation, and disease.

Velocity dependence of sensory reweighting in human balance control.

The relative contributions of proprioceptive, vestibular, and visual sensory cues to balance control change depending on their availability and reliability. This sensory reweighting is classically supported by nonlinear sway responses to increasing visual surround and/or surface tilt amplitudes. However, recent evidence indicates that visual cues are reweighted based on visual tilt velocity rather than tilt amplitude. Therefore, we designed a study to specifically test the hypothesized velocity dependence of reweighting while expanding on earlier findings for visual reweighting by testing proprioceptive reweighting for standing balance on a tilting surface. Twenty healthy young adults stood with their eyes closed on a toes-up/-down tilting platform. We designed four pseudorandom tilt sequences with either a slow (S) or a fast (F) tilt velocity and different peak-to-peak amplitudes. We used model-based interpretations of measured sway characteristics to estimate the proprioceptive sensory weight (Wprop) within each trial. In addition, root-mean-square values of measured body center of mass sway amplitude (RMS) and velocity (RMSv) were calculated for each tilt sequence. Wprop, RMS, and RMSv values varied depending on the stimulus velocity, exhibiting large effects (all Cohen's d >1.10). In contrast, we observed no significant differences across stimulus amplitudes for Wprop (Cohen's d: 0.02-0.16) and, compared with the differences in velocity, there were much smaller changes in RMS and RMSv values (Cohen's d: 0.05-0.91). These results confirmed the hypothesized velocity, rather than amplitude, dependence of sensory reweighting.NEW & NOTEWORTHY This novel study examined the velocity dependence of sensory reweighting for human balance control using support surface tilt stimuli with independently varied amplitude and velocity. Estimates of the proprioceptive contribution to standing balance, derived from model-based interpretations of sway characteristics, showed greater sensitivity to changes in surface tilt velocity than surface tilt amplitude. These results support a velocity-based mechanism underlying sensory reweighting for human balance control.

Minimal impact of chronic proprioceptive loss on implicit sensorimotor adaptation and perceived movement outcome.

Implicit sensorimotor adaptation keeps our movements well calibrated amid changes in the body and environment. We have recently postulated that implicit adaptation is driven by a perceptual error: the difference between the desired and perceived movement outcome. According to this perceptual realignment model, implicit adaptation ceases when the perceived movement outcome-a multimodal percept determined by a prior belief conveying the intended action, the motor command, and feedback from proprioception and vision-is aligned with the desired movement outcome. Here, we examined the role of proprioception in implicit motor adaptation and perceived movement outcome by examining individuals who experience deafferentation (i.e., individuals with impaired proprioception and touch). We used a modified visuomotor rotation task designed to isolate implicit adaptation and probe perceived movement outcomes throughout the experiment. Surprisingly, both implicit adaptation and perceived movement outcome were minimally impacted by chronic deafferentation, posing a challenge to the perceptual realignment model of implicit adaptation.NEW & NOTEWORTHY We tested six individuals with chronic somatosensory deafferentation on a novel task that isolates implicit sensorimotor adaptation and probes perceived movement outcome. Strikingly, both implicit motor adaptation and perceptual movement outcome were not significantly impacted by chronic deafferentation, posing a challenge for theoretical models of adaptation that involve proprioception.

Looking beyond the gene network - metabolic and mechanical cell drivers of leaf morphogenesis.

The above-ground organs in plants display a rich diversity, yet they grow to characteristic sizes and shapes. Organ morphogenesis progresses through a sequence of key events, which are robustly executed spatiotemporally as an emerging property of intrinsic molecular networks while adapting to various environmental cues. This Review focuses on the multiscale control of leaf morphogenesis. Beyond the list of known genetic determinants underlying leaf growth and shape, we focus instead on the emerging novel mechanisms of metabolic and biomechanical regulations that coordinate plant cell growth non-cell-autonomously. This reveals how metabolism and mechanics are not solely passive outcomes of genetic regulation but play instructive roles in leaf morphogenesis. Such an integrative view also extends to fluctuating environmental cues and evolutionary adaptation. This synthesis calls for a more balanced view on morphogenesis, where shapes are considered from the standpoints of geometry, genetics, energy and mechanics, and as emerging properties of the cellular expression of these different properties.

Resting state functional connectivity associated with impaired proprioception post-stroke.

Deficits in proprioception, the knowledge of limb position and movement in the absence of vision, occur in ~50% of all strokes; however, our lack of knowledge of the neurological mechanisms of these deficits diminishes the effectiveness of rehabilitation and prolongs recovery. We performed resting-state functional magnetic resonance imaging (fMRI) on stroke patients to determine functional brain networks that exhibited changes in connectivity in association with proprioception deficits determined by a Kinarm robotic exoskeleton assessment. Thirty stroke participants were assessed for proprioceptive impairments using a Kinarm robot and underwent resting-state fMRI at 1 month post-stroke. Age-matched healthy control (n = 30) fMRI data were also examined and compared to stroke data in terms of the functional connectivity of brain regions associated with proprioception. Stroke patients exhibited reduced connectivity of the supplementary motor area and the supramarginal gyrus, relative to controls. Functional connectivity of these regions plus primary somatosensory cortex and parietal opercular area was significantly associated with proprioceptive function. The parietal lobe of the lesioned hemisphere is a significant node for proprioception after stroke. Assessment of functional connectivity of this region after stroke may assist with prognostication of recovery. This study also provides potential targets for therapeutic neurostimulation to aid in stroke recovery.

Baseline GABA+ levels in areas associated with sensorimotor control predict initial and long-term motor learning progress.

Synaptic plasticity relies on the balance between excitation and inhibition in the brain. As the primary inhibitory and excitatory neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu), play critical roles in synaptic plasticity and learning. However, the role of these neurometabolites in motor learning is still unclear. Furthermore, it remains to be investigated which neurometabolite levels from the regions composing the sensorimotor network predict future learning outcome. Here, we studied the role of baseline neurometabolite levels in four task-related brain areas during different stages of motor skill learning under two different feedback (FB) conditions. Fifty-one healthy participants were trained on a bimanual motor task over 5 days while receiving either concurrent augmented visual FB (CA-VFB group, N = 25) or terminal intrinsic visual FB (TA-VFB group, N = 26) of their performance. Additionally, MRS-measured baseline GABA+ (GABA + macromolecules) and Glx (Glu + glutamine) levels were measured in the primary motor cortex (M1), primary somatosensory cortex (S1), dorsolateral prefrontal cortex (DLPFC), and medial temporal cortex (MT/V5). Behaviorally, our results revealed that the CA-VFB group outperformed the TA-VFB group during task performance in the presence of augmented VFB, while the TA-VFB group outperformed the CA-VFB group in the absence of augmented FB. Moreover, baseline M1 GABA+ levels positively predicted and DLPFC GABA+ levels negatively predicted both initial and long-term motor learning progress in the TA-VFB group. In contrast, baseline S1 GABA+ levels positively predicted initial and long-term motor learning progress in the CA-VFB group. Glx levels did not predict learning progress. Together, these findings suggest that baseline GABA+ levels predict motor learning capability, yet depending on the FB training conditions afforded to the participants.

Neuronal mechanisms regulating locomotion in adult Drosophila.

The coordinated action of multiple leg joints and muscles is required even for the simplest movements. Understanding the neuronal circuits and mechanisms that generate precise movements is essential for comprehending the neuronal basis of the locomotion and to infer the neuronal mechanisms underlying several locomotor-related diseases. Drosophila melanogaster provides an excellent model system for investigating the neuronal circuits underlying motor behaviors due to its simple nervous system and genetic accessibility. This review discusses current genetic methods for studying locomotor circuits and their function in adult Drosophila. We highlight recently identified neuronal pathways that modulate distinct forward and backward locomotion and describe the underlying neuronal control of leg swing and stance phases in freely moving flies. We also report various automated leg tracking methods to measure leg motion parameters and define inter-leg coordination, gait and locomotor speed of freely moving adult flies. Finally, we emphasize the role of leg proprioceptive signals to central motor circuits in leg coordination. Together, this review highlights the utility of adult Drosophila as a model to uncover underlying motor circuitry and the functional organization of the leg motor system that governs correct movement.

Proprioceptors of the human pericardium.

In the human organism, all functions are regulated and, therefore, require a feedback mechanism. This control involves a perception of the spatial tensile state of cardiac tissues. The presence and distribution of respective proprioceptive corpuscles have not been considered so far. Therefore, a comprehensive study of the entire human fibrous pericardium was conducted to describe the presence of proprioceptors, their density, and distribution patterns. Eight human pericardial specimens gained from our body donation program were used to create a three-dimensional map of proprioceptors in the pericardium based on their histological and immunohistochemical identification. The 3D map was generated as a volume-rendered 3D model based on magnetic resonance imaging of the pericardium, to which all identified receptors were mapped. To discover a systematic pattern in receptor distribution, statistical cluster analysis was conducted using the Scikit-learn library in Python. Ruffini-like corpuscles (RLCs) were found in all pericardia and assigned to three histological receptor localizations depending on the fibrous pericardium's layering, with no other corpuscular proprioceptors identified. Cluster analysis revealed that RLCs exhibit a specific topographical arrangement. The highest receptor concentrations occur at the ventricular bulges, where their size reaches its maximum in terms of diameter, and at the perivascular pericardial turn-up. The findings suggest that the pericardium is subject to proprioceptive control. RLCs record lateral shearing between the pericardial sublayers, and their distribution pattern enables the detection of distinct dilatation of the heart. Therefore, the pericardium might have an undiscovered function as a sensor with the RLCs as its anatomical correlate.

Distribution of nerve endings in human thumb interphalangeal joint.

This study aims to quantitatively analyze the distribution of encapsulated nerve endings in the human thumb interphalangeal (IP) joint capsule. There are three types of nerve endings. Type-I nerve endings (Ruffini-like ending) sense pressure changes, Type II (Pacini-like ending) nerve endings contribute to the kinesthetic sense, and Type III (Golgi-like ending) nerve ending provides proprioceptive information. We dissected five right thumbs IP joints from freshly frozen cadavers (5 men). The mean age of the cadavers at the time of death was 63.4 years (55-73). Sections were stained with the hematoxylin-eosin and antiprotein gene product 9.5 (PGP9.5) to identify encapsulated nerve endings. Transverse sections were cut and divided into volar, dorsal, and then into two equal parts, proximal and distal. The density of encapsulated nerve endings compared to volar versus dorsal and proximal versus distal regions was examined. This study showed that type 1 nerve endings were more common in the distal parts of the IP joint (p < 0.05). Also, type 3 nerve endings were observed in the thumb IP joint. There was no difference between regions in type II and type III nerve endings. The current study demonstrates that the distribution of encapsulated nerve endings in the IP joint is different from the PIP and DIP joints. Moreover, further studies are required to understand the thumb's physiology.

Attenuation of muscle spindle firing with artificially increased series compliance during stretch of relaxed muscle.

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.

Genetic exploration of roles of acid-sensing ion channel subtypes in neurosensory mechanotransduction including proprioception.

Although acid-sensing ion channels (ASICs) are proton-gated ion channels responsible for sensing tissue acidosis, accumulating evidence has shown that ASICs are also involved in neurosensory mechanotransduction. However, in contrast to Piezo ion channels, evidence of ASICs as mechanically gated ion channels has not been found using conventional mechanoclamp approaches. Instead, ASICs are involved in the tether model of mechanotransduction, with the channels gated via tethering elements of extracellular matrix and intracellular cytoskeletons. Methods using substrate deformation-driven neurite stretch and micropipette-guided ultrasound were developed to reveal the roles of ASIC3 and ASIC1a, respectively. Here we summarize the evidence supporting the roles of ASICs in neurosensory mechanotransduction in knockout mouse models of ASIC subtypes and provide insight to further probe their roles in proprioception.