Biology subjects

Santuz, A.

Publications and source records attributed to Santuz, A..

12 recordsLinked to original sources

bioRxiv2026

Walking on the Moon: Hypogravity drives the emergence of a proprioception-dependent locomotor state

Animals must adapt locomotion to changing environmental conditions, but how the nervous system flexibly controls movement remains unclear. Gravity provides a powerful perturbation because it alters body loading, limb dynamics, and proprioceptive feedback. Apollo astronauts often skipped on the Moon, adopting an asymmetric gait rarely used on Earth, yet the sensorimotor basis of this behaviour is unknown. Here, by studying hypogravity locomotion in humans and mice, we show that reduced gravity reveals a conserved proprioception-dependent mechanism for locomotor state expression. In humans, skipping in simulated lunar gravity is generated through flexible temporal reconfiguration of existing motor modules rather than construction of a new motor architecture. In mice, simulated lunar gravity elicited a skipping-like locomotor state, and genetic elimination of muscle proprioceptors abolished this response. Thus, hypogravity reveals how proprioceptive feedback enables flexible expression of locomotor states.

neuroscience↗

bioRxiv2025

Identification of V0g propriospinal neurons and their role in locomotor control

Propriospinal neurons relay sensory and motor information across the spinal cord and are critical components of the circuits coordinating body movements. Their diversity and roles in motor control are not clearly defined yet. In this study, by combining anatomical, molecular, and functional analyses in mice, we identified and characterized an ascending subtype of propriospinal neurons belonging to the Pitx2+ V0 family of spinal neurons. We found that Pitx2+ ascending neurons are integrated in spinal sensorimotor circuits and their function is important for the execution of precise limb movements required for effectively moving in challenging environments, like walking on a horizontal ladder or a balance beam. This work advances our understanding of the functional organization of propriospinal and V0 neurons, highlighting a previously unappreciated role in adjusting body movements to the more demanding needs of skilled locomotor tasks.

neuroscience↗

bioRxiv2023

Spatiotemporal modulation of a fixed set of muscle synergies during unpredictable and predictable gait perturbations in older adults

Muscle synergies as functional low-dimensional building blocks of the neuromotor system regulate the activation patterns of muscle groups in a modular structure during locomotion. The purpose of the current study was to explore how older adults organize locomotor muscle synergies to counteract unpredictable and predictable gait perturbations during the perturbed and the recovery steps. Sixty-three healthy older adults (71.2 {+/-} 5.2 years) participated in the study. Mediolateral and anteroposterior unpredictable and predictable perturbations during walking were introduced using a treadmill. Muscle synergies were extracted from the electromyographic activity of 13 lower limb muscles using Gaussian non-negative matrix factorization. The four basic synergies responsible for unperturbed walking (weight acceptance, propulsion, early swing and late swing) were preserved in all applied gait perturbations, yet their temporal recruitment and muscle contribution in each synergy were modified (p<0.05). These modifications were observed up to four recovery steps and were more pronounced (p<0.05) following unpredictable perturbations. The recruitment of the four basic walking synergies in the perturbed and recovery gait cycles indicates a robust neuromotor control of locomotion by using activation patterns of a few and well-known muscle synergies with specific adjustments within the synergies. The selection of pre-existing muscle synergies while adjusting the time of their recruitment during challenging locomotor conditions may facilitate the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations. Summary statementThe flexible recruitment of the four and well-known muscle synergies responsible for unperturbed walking during unpredictable and predictable gait perturbations indicates an effective way to counteract locomotor perturbations, where fast reactive responses are necessary to maintain postural stability.

neuroscience↗

bioRxiv2021

Sex-specific tuning of modular muscle activation patterns for locomotion in young and older adults

There is increasing evidence that including sex as a biological variable is of crucial importance to promote rigorous, repeatable and reproducible science. In spite of this, the body of literature that accounts for the sex of participants in human locomotion studies is small and often produces controversial results. Here, we investigated the modular organization of muscle activation patterns for human locomotion using the concept of muscle synergies with a double purpose: i) uncover possible sex-specific characteristics of motor control and ii) assess whether these are maintained in older age. We recorded electromyographic activities from 13 ipsilateral muscles of the lower limb in young and older adults of both sexes walking (young and old) and running (young) on a treadmill. The data set obtained from the 215 participants was elaborated through non-negative matrix factorization to extract the time-independent (i.e., motor modules) and time-dependent (i.e., motor primitives) coefficients of muscle synergies. We found sparse sex-specific modulations of motor control. Motor modules showed a different contribution of hip extensors, knee extensors and foot dorsiflexors in various synergies. Motor primitives were wider (i.e., lasted longer) in males in the propulsion synergy for walking (but only in young and not in older adults) and in the weight acceptance synergy for running. Moreover, the complexity of motor primitives was similar in younger adults of both sexes, but lower in older females as compared to older males. In essence, our results revealed the existence of small but defined sex-specific differences in the way humans control locomotion and that these strategies are not entirely maintained in older age.

neuroscience↗

bioRxiv2021

Differential role of spinal and supraspinal processing of proprioceptive information in mouse locomotion

Robust locomotion relies on information from proprioceptors: sensory organs that communicate the position of body parts to the spinal cord and brain. Proprioceptive circuits in the spinal cord are known to regulate locomotion in challenging environments. Yet, the regulatory importance of the brain remains less clear. Here, through mouse genetic studies and in vivo electrophysiology, we examined the role of the brain in integrating proprioceptive information during locomotion. The systemic removal of proprioceptors left the animals in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild type and characterised by longer and less accurate activation patterns. In contrast, after surgically interrupting the ascending proprioceptive projection to the brain through the dorsal column pathway, wild-type mice showed normal walking behaviour, but lost the ability to respond to external perturbations. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving safe locomotion.

neuroscience↗

bioRxiv2021

Muscle-specific economy of force generation and efficiency of work production during human running

Human running features a spring-like interaction of body and ground, enabled by elastic tendons that store mechanical energy and facilitate muscle operating conditions to minimize the metabolic cost. By experimentally assessing the operating conditions of two important muscles for running, the soleus and vastus lateralis, we investigated physiological mechanisms of muscle energy production and muscle force generation. Results showed that the soleus continuously shortened throughout the stance phase, operating as energy generator under conditions that were found to be optimal for work production: high force-length potential and enthalpy efficiency. The vastus lateralis promoted tendon energy storage and contracted nearly isometrically close to optimal length, resulting in a high force-length-velocity potential beneficial for economical force generation. The favorable operating conditions of both muscles were a result of an effective length and velocity-decoupling of fascicles and muscle-tendon unit mostly due to tendon compliance and, in the soleus, marginally by fascicle rotation.

biophysics↗

bioRxiv2020

Freely behaving mice can brake and turn during optogenetic stimulation of the Mesencephalic Locomotor Region

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSStimulation of the Mesencephalic Locomotor Region (MLR) is increasingly considered as a target to improve locomotor function in Parkinsons disease, spinal cord injury and stroke. A key function of the MLR is to control the speed of forward symmetrical locomotor movements. However, the ability of freely moving mammals to integrate environmental cues to brake and turn during MLR stimulation is poorly documented. Objective/hypothesisWe investigated whether freely behaving mice could brake or turn based on environmental cues during MLR stimulation. MethodsWe stimulated the cuneiform nucleus in mice expressing channelrhodopsin in Vglut2-positive neurons in a Cre-dependent manner (Vglut2-ChR2-EYFP) using optogenetics. We detected locomotor movements using deep learning. We used patch-clamp recordings to validate the functional expression of channelrhodopsin and neuroanatomy to visualize the stimulation sites. ResultsOptogenetic stimulation of the MLR evoked locomotion and increasing laser power increased locomotor speed. Gait diagram and limb kinematics were similar during spontaneous and optogenetic-evoked locomotion. Mice could brake and make sharp turns ([~]90) when approaching a corner during MLR stimulation in an open-field arena. The speed during the turn was scaled with the speed before the turn, and with the turn angle. In a reporter mouse, many Vglut2-ZsGreen neurons were immunopositive for glutamate in the MLR. Patch-clamp recordings in Vglut2-ChR2-EYFP mice show that blue light evoked short latency spiking in MLR neurons. ConclusionMLR glutamatergic neurons are a relevant target to improve locomotor activity without impeding the ability to brake and turn when approaching an obstacle, thus ensuring smooth and adaptable navigation. HO_SCPLOWIGHLIGHTSC_SCPLOW- Mice brake and turn when approaching the arenas corner during MLR-evoked locomotion - Speed decrease is scaled to speed before the turn during MLR-evoked locomotion - Turn angle is scaled to turn speed during MLR-evoked locomotion - Gait and limb kinematics are similar during spontaneous and MLR-evoked locomotion

neuroscience↗

bioRxiv2020

Muscle activation patterns are more constrained and regular in treadmill than in overground human locomotion

The use of motorized treadmills as convenient tools for the study of locomotion has been in vogue for many decades. However, despite the widespread presence of these devices in many scientific and clinical environments, a full consensus on their validity to faithfully substitute free overground locomotion is still missing. Specifically, little information is available on whether and how the neural control of movement is affected when humans walk and run on a treadmill as compared to overground. Here, we made use of linear and nonlinear analysis tools to extract information from electromyographic recordings during walking and running overground, and on an instrumented treadmill. We extracted synergistic activation patterns from the muscles of the lower limb via non-negative matrix factorization. We then investigated how the motor modules (or time-invariant muscle weightings) were used in the two locomotion environments. Subsequently, we examined the timing of motor primitives (or time-dependent coefficients of muscle synergies) by calculating their duration, the time of main activation, and their Hurst exponent, a nonlinear metric derived from fractal analysis. We found that motor modules were not influenced by the locomotion environment, while motor primitives resulted overall more regular in treadmill than in overground locomotion, with the main activity of the primitive for propulsion shifted earlier in time. Our results suggest that the spatial and sensory constraints imposed by the treadmill environment forced the central nervous system to adopt a different neural control strategy than that used for free overground locomotion. A data-driven indication that treadmills induce perturbations to the neural control of locomotion.

neuroscience↗

bioRxiv2020

Lower complexity of motor primitives ensures robust control of high-speed human locomotion

Walking and running are mechanically and energetically different locomotion modes. For selecting one or another, speed is a parameter of paramount importance. Yet, both are likely controlled by similar low-dimensional neuronal networks that reflect in patterned muscle activations called muscle synergies. Here, we investigated how humans synergistically activate muscles during locomotion at different submaximal and maximal speeds. We analysed the duration and complexity (or irregularity) over time of motor primitives, the temporal components of muscle synergies. We found that the challenge imposed by controlling high-speed locomotion forces the central nervous system to produce muscle activation patterns that are wider and less complex relative to the duration of the gait cycle. The motor modules, or time-independent coefficients, were redistributed as locomotion speed changed. These outcomes show that robust locomotion control at challenging speeds is achieved by modulating the relative contribution of muscle activations and producing less complex and wider control signals, whereas slow speeds allow for more irregular control.

neuroscience↗

bioRxiv2020

Fractal analysis of muscle activity patterns during locomotion: pitfalls and how to avoid them

Time-dependent physiological data, such as electromyogram (EMG) recordings from multiple muscles, is often difficult to interpret objectively. Here, we used EMG data gathered during mouse locomotion to investigate the effects of calculation parameters and data quality on two metrics for fractal analysis: the Higuchis fractal dimension (HFD) and the Hurst exponent (H). A curve is fractal if it repeats itself at every scale or, in other words, if its shape remains unchanged when zooming in the curve at every zoom level. Many linear and nonlinear analysis methods are available, each of them aiming at the explanation of different data features. In recent years, fractal analysis has become a powerful nonlinear tool to extract information from physiological data not visible to the naked eye. It can present, however, some dangerous pitfalls that can lead to misleading interpretations. To calculate the HFD and the H, we have extracted muscle synergies from normal and mechanically perturbed treadmill locomotion from the hindlimb of adult mice. Then, we used one set per condition (normal and perturbed walking) of the obtained time-dependent coefficients to create surrogate data with different fluctuations over the original mean signal. Our analysis shows that HFD and H are exceptionally sensitive to the presence or absence of perturbations to locomotion. However, both metrics suffer from variations in their value depending on the parameters used for calculations and the presence of quasi-periodic elements in the time series. We discuss those issues giving some simple suggestions to reduce the chance of misinterpreting the outcomes. New & NoteworthyDespite the lack of consensus on how to perform fractal analysis of physiological time series, many studies rely on this technique. Here, we shed light on the potential pitfalls of using the Higuchis fractal dimension and the Hurst exponent. We expose and suggest how to solve the drawbacks of such methods when applied to data from normal and perturbed locomotion by combining in vivo recordings and computational approaches.

neuroscience↗

bioRxiv2019

Humans exploit robust locomotion by improving the stability of control signals

Is the control of movement less stable when we walk or run in challenging settings? One might intuitively answer affirmatively, given that adding constraints to locomotion (e.g. rough terrain, age-related impairments, etc.) imply less stable movements. We investigated how young and old humans synergistically activate muscles during locomotion, when different perturbation levels are introduced. Of these control signals, called muscle synergies, we then analyzed the stability over time. Surprisingly, we found that perturbations and older age force the central nervous system to produce more stable signals. These outcomes show that robust locomotion in challenging settings is achieved by increasing the stability of control signals, whereas easier tasks allow for more unstable control.

neuroscience↗

bioRxiv2018

Modular organization of the murine locomotor pattern in presence and absence of sensory feedback from muscle spindles

For exploiting terrestrial and aquatic locomotion, vertebrates must build their locomotor patterns based on an enormous amount of variables. The great number of muscles and joints, together with the constant need for sensory feedback information (e.g. proprioception), make the task of creating and controlling movement a problem with overabundant degrees of freedom. It is widely accepted that the central nervous system might simplify the creation and control of movement. This could happen through the generation of activation patterns, which are common to many different muscles, rather than specific to individual muscles. These activation patterns, called muscle synergies, can be extracted from electromyographic data and describe the modular organization of movement. We extracted muscle synergies from the hindlimb muscle activities of wild type and genetically modified mice, in which sensory feedback from muscle spindles is eliminated. Muscle spindle-deficient mice underwent a modification of the temporal structure (motor primitives) of muscle synergies that resulted in diminished functionality during walking. In addition, both the temporal and spatial components (motor modules) of muscle synergies were severely affected when external perturbations were introduced of when animals were immersed in water. These findings show that group Ia/II sensory feedback from muscle spindles regulates motor function in normal and perturbed walking. Moreover, when group Ib Golgi tendon organ feedback is lacking due to the reduction of gravitational load in conditions of enhanced buoyancy, the modular organization of swimming is almost completely compromised.\n\nSignificance statementLocomotion on land and in water requires the coordination of a great number of muscle activations and joint movements. Moreover, constant feedback about the position of own body parts in relation to the surrounding environment and the body itself (proprioception) is required to maintain stability and avoid failure. The theory of muscle synergies states that the central nervous system might control muscles in orchestrated groups (synergies) rather than individually. We used this concept on genetically modified mice, lacking one of the two classes of proprioceptors. Our results provide evidence that proprioceptive feedback is required by the central nervous system to accurately tune the modular organization of locomotion.

neuroscience↗