Differential impact of diesel exhaust particles on glutamatergic and dopaminergic neurons in Caenorhabditis elegans: A neurodegenerative perspective.

The growing body of evidence links exposure to particulate matter pollutants with an increased risk of neurodegenerative diseases. In the present study, we investigated whether diesel exhaust particles can induce neurobehavioral alterations associated with neurodegenerative effects on glutamatergic and dopaminergic neurons in Caenorhabditis elegans (C. elegans). Exposure to DEP at concentrations of 0.167 µg/cm2 and 1.67 µg/cm2 resulted in significant developmental delays and altered locomotion behaviour. These effects were accompanied by discernible alterations in the expressions of antioxidant genes sod-3 and gst-4 observed in transgenic strains. Behaviour analysis demonstrated a significant reduction in average speed (p < 0.001), altered paths, and decreased swimming activities (p < 0.01), particularly at mid and high doses. Subsequent assessment of neurodegeneration markers in glutamatergic (DA1240) and dopaminergic (BZ555) transgenic worms revealed notable glutamatergic neuron degeneration at 0.167 µg/cm2 (∼30 % moderate, ∼20 % advanced) and 1.67 µg/cm2 (∼28 % moderate, ∼24 % advanced, p < 0.0001), while dopaminergic neurons exhibited structural deformities (∼16 %) without significant degeneration in terms of blebs and breaks. Furthermore, in silico docking simulations suggest the presence of an antagonistic competitive inhibition induced by DEP in the evaluated neuro-targets, stronger for the glutamatergic transporter than for the dopaminergic receptor from the comparative binding affinity point of view. The results underscore DEP's distinctive neurodegenerative effects and suggest a link between locomotion defects and glutamatergic neurodegeneration in C. elegans, providing insights into environmental health risks assessment.

Real-world humanoid locomotion with reinforcement learning.

Humanoid robots that can autonomously operate in diverse environments have the potential to help address labor shortages in factories, assist elderly at home, and colonize new planets. Although classical controllers for humanoid robots have shown impressive results in a number of settings, they are challenging to generalize and adapt to new environments. Here, we present a fully learning-based approach for real-world humanoid locomotion. Our controller is a causal transformer that takes the history of proprioceptive observations and actions as input and predicts the next action. We hypothesized that the observation-action history contains useful information about the world that a powerful transformer model can use to adapt its behavior in context, without updating its weights. We trained our model with large-scale model-free reinforcement learning on an ensemble of randomized environments in simulation and deployed it to the real-world zero-shot. Our controller could walk over various outdoor terrains, was robust to external disturbances, and could adapt in context.

Viability leads to the emergence of gait transitions in learning agile quadrupedal locomotion on challenging terrains.

Quadruped animals are capable of seamless transitions between different gaits. While energy efficiency appears to be one of the reasons for changing gaits, other determinant factors likely play a role too, including terrain properties. In this article, we propose that viability, i.e., the avoidance of falls, represents an important criterion for gait transitions. We investigate the emergence of gait transitions through the interaction between supraspinal drive (brain), the central pattern generator in the spinal cord, the body, and exteroceptive sensing by leveraging deep reinforcement learning and robotics tools. Consistent with quadruped animal data, we show that the walk-trot gait transition for quadruped robots on flat terrain improves both viability and energy efficiency. Furthermore, we investigate the effects of discrete terrain (i.e., crossing successive gaps) on imposing gait transitions, and find the emergence of trot-pronk transitions to avoid non-viable states. Viability is the only improved factor after gait transitions on both flat and discrete gap terrains, suggesting that viability could be a primary and universal objective of gait transitions, while other criteria are secondary objectives and/or a consequence of viability. Moreover, our experiments demonstrate state-of-the-art quadruped robot agility in challenging scenarios.

Legged robots beyond bioinspiration.

Advances in engineering enable wheeled-legged hybrid locomotion, an achievement not feasible in biological systems.

Delay in the fine-tuning of locomotion in infants with meconium positive to biomarkers of alcohol exposure: a pilot study.

INTRODUCTION: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women. MATERIALS AND METHODS: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites. RESULTS: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities. CONCLUSIONS: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.

Indirect and direct cannabinoid agonists differentially affect mesolimbic dopamine release and related behaviors.

The cannabinoid system is being researched as a potential pharmaceutical target for a multitude of disorders. The present study examined the effect of indirect and direct cannabinoid agonists on mesolimbic dopamine release and related behaviors in C57BL/6J (B6) mice. The indirect cannabinoid agonist N-arachidonoyl serotonin (AA-5-HT) indirectly agonizes the cannabinoid system by preventing the metabolism of endocannabinoids through fatty acid amide hydrolase inhibition while also inhibiting transient receptor potential vanilloid Type 1 channels. Effects of AA-5-HT were compared with the direct cannabinoid receptor Type 1 agonist arachidonoyl-2'-chloroethylamide (ACEA). In Experiment 1, mice were pretreated with seven daily injections of AA-5-HT, ACEA, or vehicle prior to assessments of locomotor activity using open field (OF) testing and phasic dopamine release using in vivo fixed potential amperometry. Chronic exposure to AA-5-HT did not alter locomotor activity or mesolimbic dopamine functioning. Chronic exposure to ACEA decreased rearing and decreased phasic dopamine release while increasing the dopaminergic response to cocaine. In Experiment 2, mice underwent AA-5-HT, ACEA, or vehicle conditioned place preference, then saccharin preference testing, a measure commonly associated with anhedonia. Mice did not develop a conditioned place preference or aversion for AA-5-HT or ACEA, and repeated exposure to AA-5-HT or ACEA did not alter saccharin preference. Altogether, the findings suggest that neither of these drugs induce behaviors that are classically associated with abuse liability in mice; however, direct cannabinoid receptor Type 1 agonism may play more of a role in mediating mesolimbic dopamine functioning than indirect cannabinoid agonism. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of ingesting large prey on the kinematics of rectilinear locomotion in Boa constrictor.

Large and stout snakes commonly consume large prey and use rectilinear crawling; yet, whether body wall distention after feeding impairs rectilinear locomotion is poorly understood. After eating large prey (30-37% body mass), all Boa constrictor tested could perform rectilinear locomotion in the region with the food bolus despite a greatly increased distance between the ribs and the ventral skin that likely lengthens muscles relevant to propulsion. Unexpectedly, out of 11 kinematic variables, only two changed significantly (P<0.05) after feeding: cyclic changes in snake height increased by more than 1.5 times and the longitudinal movements of the ventral skin relative to the skeleton decreased by more than 25%. Additionally, cyclic changes in snake width suggest that the ribs are active and mobile during rectilinear locomotion, particularly in fed snakes, but also in unfed snakes. These kinematic changes suggest that rectilinear actuators reorient more vertically and undergo smaller longitudinal excursions following large prey ingestion, both of which likely act to reduce elongation of these muscles that may otherwise experience substantial strain.

Simulation of Human Movement in Zero Gravity.

In the era of expanding manned space missions, understanding the biomechanical impacts of zero gravity on human movement is pivotal. This study introduces a novel and cost-effective framework that demonstrates the application of Microsoft's Azure Kinect body tracking technology as a motion input generator for subsequent OpenSim simulations in weightlessness. Testing rotations, locomotion, coordination, and martial arts movements, we validate the results' realism under the constraints of angular and linear momentum conservation. While complex, full-body coordination tasks face limitations in a zero gravity environment, our findings suggest possible approaches to device-free exercise routines for astronauts and reveal insights into the feasibility of hand-to-hand combat in space. However, some challenges remain in distinguishing zero gravity effects in the simulations from discrepancies in the captured motion input or forward dynamics calculations, making a comprehensive validation difficult. The paper concludes by highlighting the framework's practical potential for the future of space mission planning and related research endeavors, while also providing recommendations for further refinement.

The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors.

The role of RNA Binding Motif Protein 8a (RBM8A), an exon junction complex (EJC) component, in neurodevelopmental disorders has been increasingly studied for its crucial role in regulating multiple levels of gene expression. It regulates mRNA splicing, translation, and mRNA degradation and influences embryonic development. RBM8A protein is expressed in both neurons and astrocytes, but little is known about RBM8A's specific role in glial fibrillary acid protein (GFAP)-positive astrocytes. To address the role of RBM8A in astrocytes, we generated a conditional heterozygous knockout (KO) mouse line of Rbm8a in astrocytes using a GFAP-cre line. We confirmed a decreased expression of RBM8A in astrocytes of heterozygous conditional KO mice via RT-PCR and Sanger sequencing, as well as qRT-PCR, immunohistochemistry, and Western blot. Interestingly, these mice exhibit significantly increased movement and mobility, alongside sex-specific altered anxiety in the open field test (OFT) and elevated plus maze (OPM) tests. These tests, along with the rotarod test, suggest that these mice have normal motor coordination but hyperactive phenotypes. In addition, the haploinsufficiency of Rbm8a in astrocytes leads to a sex-specific change in astrocyte density in the dentate gyrus. This study further reveals the contribution of Rbm8a deletion to CNS pathology, generating more insights via the glial lens of an Rbm8a model of neurodevelopmental disorder.

S-shaped rolling gait designed using curve transformations of a snake robot for climbing on a bifurcated pipe.

In this work, we focus on overcoming the challenge of a snake robot climbing on the outside of a bifurcated pipe. Inspired by the climbing postures of biological snakes, we propose an S-shaped rolling gait designed using curve transformations. For this gait, the snake robot's body presenting an S-shaped curve is wrapped mainly around one side of the pipe, which leaves space for the fork of the pipe. To overcome the difficulty in constructing and clarifying the S-shaped curve, we present a method for establishing the transformation between a plane curve and a 3D curve on a cylindrical surface. Therefore, we can intuitively design the curve in 3D space, while analytically calculating the geometric properties of the curve in simple planar coordinate systems. The effectiveness of the proposed gait is verified by actual experiments. In successful configuration scenarios, the snake robot could stably climb on the pipe and efficiently cross or climb to the bifurcation while maintaining its target shape.

Spatiotemporal modulation of a common 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 steps 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 for 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 improve the effectiveness to deal with perturbations and promote the transfer of adaptation between different kinds of perturbations.

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn.

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.

Multiple forces facilitate the aquatic acrobatics of grasshopper and bioinspired robot.

Aquatic locomotion is challenging for land-dwelling creatures because of the high degree of fluidity with which the water yields to loads. We surprisingly found that the Chinese rice grasshopper Oxya chinensis, known for its terrestrial acrobatics, could swiftly launch itself off the water's surface in around 25 ms and seamlessly transition into flight. Biological observations showed that jumping grasshoppers use their front and middle legs to tilt up bodies first and then lift off by propelling the water toward the lower back with hind legs at angular speeds of up to 18°/ms, whereas the swimming grasshoppers swing their front and middle legs in nearly horizontal planes and move hind legs less violently (~8°/ms). Force measurement and model analysis indicated that the weight support could be achieved by hydrostatics which are proportionate to the mass of the grasshoppers, while the propulsions for motion are derived from the controlled limb-water interactions (i.e., the hydrodynamics). After learning the structural and behavioral strategies of the grasshoppers, a robot was created and was capable of swimming and jumping on the water surface like the insects, further demonstrating the effectiveness of decoupling the challenges of aquatic locomotion by the combined use of the static and dynamic hydro forces. This work not only uncovered the combined mechanisms responsible for facilitating aquatic acrobatics in this species but also laid a foundation for developing bioinspired robots that can locomote across multiple media.

Robot motor learning shows emergence of frequency-modulated, robust swimming with an invariant Strouhal number.

Fish locomotion emerges from diverse interactions among deformable structures, surrounding fluids and neuromuscular activations, i.e. fluid-structure interactions (FSI) controlled by fish's motor systems. Previous studies suggested that such motor-controlled FSI may possess embodied traits. However, their implications in motor learning, neuromuscular control, gait generation, and swimming performance remain to be uncovered. Using robot models, we studied the embodied traits in fish-inspired swimming. We developed modular robots with various designs and used central pattern generators (CPGs) to control the torque acting on robot body. We used reinforcement learning to learn CPG parameters for maximizing the swimming speed. The results showed that motor frequency converged faster than other parameters, and the emergent swimming gaits were robust against disruptions applied to motor control. For all robots and frequencies tested, swimming speed was proportional to the mean undulation velocity of body and caudal-fin combined, yielding an invariant, undulation-based Strouhal number. The Strouhal number also revealed two fundamental classes of undulatory swimming in both biological and robotic fishes. The robot actuators were also demonstrated to function as motors, virtual springs and virtual masses. These results provide novel insights in understanding fish-inspired locomotion.

Locomotion Efficiency in Children With Cerebral Palsy Experiencing Limited Gross Motor Function: Walking Versus Cycling.

PURPOSE: This study compares cycling and walking efficiency, and energy expenditure in children with bilateral spastic cerebral palsy (CP). In children with CP, locomotion with body weight support aids such as a tricycle is a potential alternative for less exhausting movements. METHODS: Nine children with CP traveled at comfortable speed for 6 minutes by cycling and walking. The energy expenditure index (EEI) and the percentage of the reserve heart rate (%HRR) were calculated. RESULTS: The EEI was lower while cycling than walking, the traveled distance was higher while cycling than walking, and %HRR remained similar between cycling and walking. CONCLUSION: Cycling appears an efficient alternative to walking for children with CP for adapted school environments and in the community.

Comparative kinetics of humans and non-human primates during vertical climbing.

Climbing represents a critical behavior in the context of primate evolution. However, anatomically modern human populations are considered ill-suited for climbing. This adaptation can be attributed to the evolution of striding bipedalism, redirecting anatomical traits away from efficient climbing. Although prior studies have speculated on the kinetic consequences of this anatomical reorganization, there is a lack of data on the force profiles of human climbers. This study utilized high-speed videography and force plate analysis to assess single limb forces during climbing from 44 human participants of varying climbing experience and compared these data with climbing data from eight species of non-human primates (anthropoids and strepsirrhines). Contrary to expectations, experience level had no significant effect on the magnitude of single limb forces in humans. Experienced climbers did, however, demonstrate a predictable relationship between center of mass position and peak normal forces, suggesting a better ability to modulate forces during climbing. Humans exhibited significantly higher peak propulsive forces in the hindlimb compared with the forelimb and greater hindlimb dominance overall compared with non-human primates. All species sampled demonstrated exclusively tensile forelimbs and predominantly compressive hindlimbs. Strepsirrhines exhibited a pull-push transition in normal forces, while anthropoid primates, including humans, did not. Climbing force profiles are remarkably stereotyped across humans, reflecting the universal mechanical demands of this form of locomotion. Extreme functional differentiation between forelimbs and hindlimbs in humans may help to explain the evolution of bipedalism in ancestrally climbing hominoids.

Tapping into the human spinal locomotor centres with transspinal stimulation.

Human locomotion is controlled by spinal neuronal networks of similar properties, function, and organization to those described in animals. Transspinal stimulation affects the spinal locomotor networks and is used to improve standing and walking ability in paralyzed people. However, the function of locomotor centers during transspinal stimulation at different frequencies and intensities is not known. Here, we document the 3D joint kinematics and spatiotemporal gait characteristics during transspinal stimulation at 15, 30, and 50 Hz at sub-threshold and supra-threshold stimulation intensities. We document the temporal structure of gait patterns, dynamic stability of joint movements over stride-to-stride fluctuations, and limb coordination during walking at a self-selected speed in healthy subjects. We found that transspinal stimulation (1) affects the kinematics of the hip, knee, and ankle joints, (2) promotes a more stable coordination at the left ankle, (3) affects interlimb coordination of the thighs, and (4) intralimb coordination between thigh and foot, (5) promotes greater dynamic stability of the hips, (6) increases the persistence of fluctuations in step length variability, and lastly (7) affects mechanical walking stability. These results support that transspinal stimulation is an important neuromodulatory strategy that directly affects gait symmetry and dynamic stability. The conservation of main effects at different frequencies and intensities calls for systematic investigation of stimulation protocols for clinical applications.

Dimensionality of locomotor behaviors in developing C. elegans.

Adult animals display robust locomotion, yet the timeline and mechanisms of how juvenile animals acquire coordinated movements and how these movements evolve during development are not well understood. Recent advances in quantitative behavioral analyses have paved the way for investigating complex natural behaviors like locomotion. In this study, we tracked the swimming and crawling behaviors of the nematode Caenorhabditis elegans from postembryonic development through to adulthood. Our principal component analyses revealed that adult C. elegans swimming is low dimensional, suggesting that a small number of distinct postures, or eigenworms, account for most of the variance in the body shapes that constitute swimming behavior. Additionally, we found that crawling behavior in adult C. elegans is similarly low dimensional, corroborating previous studies. Further, our analysis revealed that swimming and crawling are distinguishable within the eigenworm space. Remarkably, young L1 larvae are capable of producing the postural shapes for swimming and crawling seen in adults, despite frequent instances of uncoordinated body movements. In contrast, late L1 larvae exhibit robust coordination of locomotion, while many neurons crucial for adult locomotion are still under development. In conclusion, this study establishes a comprehensive quantitative behavioral framework for understanding the neural basis of locomotor development, including distinct gaits such as swimming and crawling in C. elegans.

Center of mass position does not drive energetic costs during climbing.

Climbing animals theoretically should optimize the energetic costs of vertical climbing while also maintaining stability. Many modifications to climbing behaviors have been proposed as methods of satisfying these criteria, focusing on controlling the center of mass (COM) during ascent. However, the link between COM movements and metabolic energy costs has yet to be evaluated empirically. In this study, we manipulated climbing conditions across three experimental setups to elicit changes in COM position, and measured the impact of these changes upon metabolic costs across a sample of 14 humans. Metabolic energy was assessed via open flow respirometry, while COM movements were tracked both automatically and manually. Our findings demonstrate that, despite inducing variation in COM position, the energetic costs of climbing remained consistent across all three setups. Differences in energetic costs were similarly not affected by body mass; however, velocity had a significant impact upon both cost of transport and cost of locomotion, but such a relationship disappeared when accounting for metabolic costs per stride. These findings suggest that climbing has inescapable metabolic demands driven by gaining height, and that attempts to mitigate such a cost, with perhaps the exception of increasing speed, have only minimal impacts. We also demonstrate that metabolic and mechanical energy costs are largely uncorrelated. Collectively, we argue that these data refute the idea that efficient locomotion is the primary aim during climbing. Instead, adaptations towards effective climbing should focus on stability and reducing the risk of falling, as opposed to enhancing the metabolic efficiency of locomotion.

DeepLabCut-based daily behavioural and posture analysis in a cricket.

Circadian rhythms are indispensable intrinsic programs that regulate the daily rhythmicity of physiological processes, such as feeding and sleep. The cricket has been employed as a model organism for understanding the neural mechanisms underlying circadian rhythms in insects. However, previous studies measuring rhythm-controlled behaviours only analysed locomotive activity using seesaw-type and infrared sensor-based actometers. Meanwhile, advances in deep learning techniques have made it possible to analyse animal behaviour and posture using software that is devoid of human bias and does not require physical tagging of individual animals. Here, we present a system that can simultaneously quantify multiple behaviours in individual crickets - such as locomotor activity, feeding, and sleep-like states - in the long-term, using DeepLabCut, a supervised machine learning-based software for body keypoints labelling. Our system successfully labelled the six body parts of a single cricket with a high level of confidence and produced reliable data showing the diurnal rhythms of multiple behaviours. Our system also enabled the estimation of sleep-like states by focusing on posture, instead of immobility time, which is a conventional parameter. We anticipate that this system will provide an opportunity for simultaneous and automatic prediction of cricket behaviour and posture, facilitating the study of circadian rhythms.