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Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. Because individual muscles may be used in many different behaviors, MN activity must be flexibly coordinated by dedicated premotor circuitry, the organization of which remains largely unknown. Here, we use comprehensive reconstruction of neuron anatomy and synaptic connectivity from volumetric electron microscopy (i.e., connectomics) to analyze the wiring logic of motor circuits controlling theDrosophilaleg and wing. We find that both leg and wing premotor networks are organized into modules that link MNs innervating muscles with related functions. However, the connectivity patterns within leg and wing motor modules are distinct. Leg premotor neurons exhibit proportional gradients of synaptic input onto MNs within each module, revealing a novel circuit basis for hierarchical MN recruitment. In comparison, wing premotor neurons lack proportional synaptic connectivity, which may allow muscles to be recruited in different combinations or with different relative timing. By comparing the architecture of distinct limb motor control systems within the same animal, we identify common principles of premotor network organization and specializations that reflect the unique biomechanical constraints and evolutionary origins of leg and wing motor control.

Like the vertebrate spinal cord, the insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we applied automated tools for electron microscopy (EM) volume alignment, neuron reconstruction, and synapse prediction to create a draft connectome of theDrosophilaVNC. To interpret the VNC connectome, it is crucial to know its relationship with the rest of the body. We therefore mapped the muscle targets of leg and wing motor neurons in the connectome by comparing their morphology to genetic driver lines, dye fills, and x-ray holographic nano-tomography volumes of the fly leg and wing. Knowing the outputs of the connectome allowed us to identify neural circuits that coordinate the wings with the middle and front legs during escape takeoff. We provide the draft VNC connectome and motor neuron atlas, along with tools for programmatic and interactive access, as community resources.

Horticultural performance of eleven blackberry cultivars, including two primocane-fruiting cultivars, was evaluated over three years after fruiting began at the Musser Fruit Research Center in Sout...

Control of adaptive walking requires the integration of sensory signals of muscle force and load. We have studied how mechanoreceptors (tibial campaniform sensilla) encode 'naturalistic' stimuli derived from joint torques of stick insects walking on a horizontal substrate. Previous studies showed that forces applied to the legs using the mean torque profiles of a proximal joint were highly effective in eliciting motor activities. However, substantial variations in torque direction and magnitude occurred at the more distal femoro-tibial joint, which can generate braking or propulsive forces and provide lateral stability. To determine how these forces are encoded, we utilized torque waveforms of individual steps that had maximum values in stance in the directions of flexion or extension. Analysis of kinematic data showed that the torques in different directions tended to occur in different ranges of joint angles. Variations within stance were not accompanied by comparable changes in joint angle but often reflected vertical ground reaction forces and leg support of body load. Application of torque waveforms elicited sensory discharges with variations in firing frequency similar to those seen in freely walking insects. All sensilla directionally encoded the dynamics of force increases and showed hysteresis to transient force decreases. Smaller receptors exhibited more tonic firing. Our findings suggest that dynamic sensitivity in force feedback can modulate ongoing muscle activities to stabilize distal joints when large forces are generated at proximal joints. Further, use of 'naturalistic' stimuli can reproduce characteristics seen in freely moving animals that are absent in conventional restrained preparations.

This work elucidates the impacts of model construction choices on turbulence characteristics and solution fidelity in the simulation of coupled freestream and porous turbulent flows. A freestream-porewater interface is modeled numerically as a matrix of regularly spaced spheres submerged in a surrounding flow. Simulations are conducted to solve the continuity and momentum equations via Large Eddy Simulation (LES) using the Control Volume Finite Element Method (CVFEM) on an unstructured, surface-conforming mesh, and simulated flow fields are compared with experimental results. Key parameters are identified, allowing for model creation recommendations. A mesh refinement study is performed, and characteristic required mesh sizes in both the bed and the freestream are identified that achieve a good trade-off between accuracy and efficiency. Additionally, it is shown that similar to wall-bounded flows, the computational domain for a coupled freestream and porous flow must be sufficiently large to capture the relevant largest-sized eddies and to avoid the spanwise locking of flow structures; such structures may affect the flow field in the pores as well as in the freestream. Dimensions of 7.5H × 3.5H × H, where H is the freestream height, are found to give satisfactory comparison with experimental results for the cases studied. Finally, it is found that the wall-adapting local eddy-viscosity (WALE) turbulence closure scheme is better able to model the fluid velocity in the problem domain compared with the Smagorinsky model. Failure to select the proper turbulence closure model or domain size leads to a misrepresentation of the turbulent structures. Because of the strong coupling between the porewater flow and the freestream, these modeling errors propagate in both flow regions.

Many sensory systems are tuned to specific parameters of behaviors and have effects that are task-specific. We have studied how force feedback contributes to activation of synergist muscles in serially homologous legs of stick insects. Forces were applied using conventional half sine or ramp and hold functions. We also utilized waveforms of joint torques calculated from experiments in freely walking animals. In all legs, forces applied to either the tarsus (foot) or proximal leg segment (trochanter) activated synergist muscles that generate substrate grip and support but coupling of the depressor muscle to tarsal forces was weak in the front legs. Activation of trochanteral receptors using ramp and hold functions generated positive feedback to the depressor muscle in all legs when animals were induced to seek substrate grip. However, discharges of the synergist flexor muscle showed adaptation at moderate force levels. In contrast, application of forces using torque waveforms, which do not have a static hold phase, produced sustained discharges in muscle synergies with little adaptation. Firing frequencies reflected the magnitude of ground reaction forces, were graded to changes in force amplitude and could also be modulated by transient force perturbations added to the waveforms. Comparison of synergist activation by torques and ramp and hold functions revealed a strong influence of force dynamics (dF/dt). These studies support the idea that force receptors can act to synchronously tune muscle synergies to the range of force magnitudes and dynamics that occur in each leg according to their specific use in behaviorMany sensory systems are tuned to specific parameters of behaviors and have effects that are task-specific. We have studied how force feedback contributes to activation of synergist muscles in serially homologous legs of stick insects. Forces were applied using conventional half sine or ramp and hold functions. We also utilized waveforms of joint torques calculated from experiments in freely walking animals. In all legs, forces applied to either the tarsus (foot) or proximal leg segment (trochanter) activated synergist muscles that generate substrate grip and support but coupling of the depressor muscle to tarsal forces was weak in the front legs. Activation of trochanteral receptors using ramp and hold functions generated positive feedback to the depressor muscle in all legs when animals were induced to seek substrate grip. However, discharges of the synergist flexor muscle showed adaptation at moderate force levels. In contrast, application of forces using torque waveforms, which do not have a static hold phase, produced sustained discharges in muscle synergies with little adaptation. Firing frequencies reflected the magnitude of ground reaction forces, were graded to changes in force amplitude and could also be modulated by transient force perturbations added to the waveforms. Comparison of synergist activation by torques and ramp and hold functions revealed a strong influence of force dynamics (dF/dt). These studies support the idea that force receptors can act to synchronously tune muscle synergies to the range of force magnitudes and dynamics that occur in each leg according to their specific use in behavior

Control of forces is essential in both animals and walking machines. Insects measure forces as strains in their exoskeletons via campaniform sensilla (CS). Deformations of cuticular caps embedded in the exoskeleton excite afferents that project to the central nervous system. CS afferent firing frequency (i.e. ‘discharge’) is highly dynamic, correlating with the rate of change of the force. Discharges adapt over time to tonic forces and exhibit hysteresis during cyclic loading. In this study we characterized a phenomenological model that predicts CS discharge, in which discharge is proportional to the instantaneous stimulus force relative to an adaptive variable. In contrast to previous studies of sensory adaptation, our model (1) is nonlinear and (2) reproduces the characteristic power-law adaptation with first order dynamics only (i.e. no ‘fractional derivatives’ are required to explain dynamics). We solve the response of the system analytically in multiple cases and use these solutions to derive the dynamics of the adaptive variable. We show that the model can reproduce responses of insect CS to many different force stimuli after being tuned to reproduce only one response, suggesting that the model captures the underlying dynamics of the system. We show that adaptation to tonic forces, rate-sensitivity, and hysteresis are different manifestations of the same underlying mechanism: the adaptive variable. We tune the model to replicate the dynamics of three different CS groups from two insects (cockroach and stick insect), demonstrating that it is generalizable. We also invert the model to estimate the stimulus force given the discharge recording from the animal. We discuss the adaptive neural and mechanical processes that the model may mimic and the model’s use for understanding the role of load feedback in insect motor control. A preliminary model and results were previously published in the proceedings of the Conference on Biohybrid and Biomimetic Systems.

Dexterous motor control requires feedback from proprioceptors, internal mechanosensory neurons that sense the body’s position and movement. An outstanding question in neuroscience is how diverse proprioceptive feedback signals contribute to flexible motor control. Genetic tools now enable targeted recording and perturbation of proprioceptive neurons in behaving animals; however, these experiments can be challenging to interpret, due to the tight coupling of proprioception and motor control. Here, we argue that understanding the role of proprioceptive feedback in controlling behavior will be aided by the development of multiscale models of sensorimotor loops. We review current phenomenological and structural models for proprioceptor encoding and discuss how they may be integrated with existing models of posture, movement, and body state estimation.

The relative motion between the surface of an object and our fingers produces patterns of skin deformation such as stretch, indentation, and vibrations. In this study, we hypothesized that motion-induced vibrations are combined with other tactile cues for the discrimination of tactile speed. Specifically, we hypothesized that vibrations provide a critical cue to tactile speed on surfaces lacking individually detectable features like dots or ridges. Thus masking vibrations unrelated to slip motion should impair the discriminability of tactile speed, and the effect should be surface-dependent. To test this hypothesis, we measured the precision of participants in discriminating the speed of moving surfaces having either a fine or a ridged texture, while adding masking vibratory noise in the working range of the fast-adapting mechanoreceptive afferents. Vibratory noise significantly reduced the precision of speed discrimination, and the effect was much stronger on the fine-textured than on the ridged surface. On both surfaces, masking vibrations at intermediate frequencies of 64 Hz (65-μm peak-to-peak amplitude) and 128 Hz (10 μm) had the strongest effect, followed by high-frequency vibrations of 256 Hz (1 μm) and low-frequency vibrations of 32 Hz (50 and 25 μm). These results are consistent with our hypothesis that slip-induced vibrations concur to the discrimination of tactile speed.

In recent years, research on insect motor behaviour - locomotion in particular - has provided a number of important new insights, many of which became possible because of methodological advances in motion capture of unrestrained moving insects. Behavioural analyses have not only backed-up neurophysiological analyses of the underlying mechanisms at work, they have also highlighted the complexity and variability of leg movements in naturalistic, unrestrained behaviour. Here, we argue that the variability of unrestrained motor behaviour should be considered a sign of behavioural flexibility. Assuming that variation of movement-related parameters is governed by neural mechanisms, behavioural analyses can complement neurophysiological investigations, for example by (i) dissociating distinct movement episodes based on functional and statistical grounds, (ii) quantifying when and how transitions between movement episodes occur, and (iii) dissociating temporal and spatial coordination. The present review emphasizes the importance of considering the functional diversity of limb movements in insect behaviour. In particular, we highlight the fundamental difference between leg movements that generate interaction forces as opposed to those that do not. On that background, we discuss the spatially continuous modulation of swing movements and the quasi-rhythmic nature of stepping across insect orders. Based on examples of motor flexibility in stick insects, we illustrate the relevance of behaviour-based approaches for computational modelling of a rich and adaptive movement repertoire. Finally, we emphasize the intimate interplay of locomotion and near-range exploration. We propose that this interplay, through continuous integration of distributed, multimodal sensory feedback, is key to locomotor flexibility.

Animals rely on an adaptive coordination of legs during walking. However, which specific mechanisms underlie coordination during natural locomotion remains largely unknown. One hypothesis is that legs can be coordinated mechanically based on a transfer of body load from one leg to another. To test this hypothesis, we simultaneously recorded leg kinematics, ground reaction forces and muscle activity in freely walking stick insects (Carausius morosus). Based on torque calculations, we show that load sensors (campaniform sensilla) at the proximal leg joints are well suited to encode the unloading of the leg in individual steps. The unloading coincides with a switch from stance to swing muscle activity, consistent with a load reflex promoting the stance-to-swing transition. Moreover, a mechanical simulation reveals that the unloading can be ascribed to the loading of a specific neighbouring leg, making it exploitable for inter-leg coordination. We propose that mechanically mediated load-based coordination is used across insects analogously to mammals.

The integration of information from dynamic sensory structures operating on a moving body is a challenge for locomoting animals and engineers seeking to design agile robots. As a tactile sensor is a physical linkage mediating mechanical interactions between body and environment, mechanical tuning of the sensor is critical for effective control. We determined the open-loop dynamics of a tactile sensor, specifically the antenna of the American cockroach, Periplaneta americana, an animal that escapes predators by using its antennae during rapid closed-loop tactilely mediated course control. Geometrical measurements and static bending experiments revealed an exponentially decreasing flexural stiffness (EI) from base to tip. Quasi-static experiments with a physical model support the hypothesis that a proximodistally decreasing EI can simplify control by increasing preview distance and allowing effective mapping to a putative control variable - body-to-wall distance - compared to an antenna with constant EI. We measured the free response at the tip of the antenna following step deflections and determined that the antenna rapidly damps large deflections: over 90% of the perturbation is rejected within the first cycle, corresponding to almost one stride period during high-speed running (~50 ms). An impulse-like perturbation near the tip revealed dynamics that were characteristic of an inelastic collision, keeping the antenna in contact with an object after impact. We contend that proximodistally decreasing stiffness, high damping, and inelasticity simplify control during high-speed tactile tasks by increasing preview distance, providing a one-dimensional map between antennal bending and body-to-wall distance, and increasing the reliability of tactile information.

BACKGROUND Small bowel allografts can either be placed heterotopically or orthotopically. In heterotopic small bowel transplantation (H-SBT), the host small intestine containing a substantial amount of gut-associated lymphoid tissue is removed, whereas in conventional orthotopic small bowel transplantation (O-SBT) it is retained. This study compared the allograft survival of H-SBT and O-SBT and evaluated the effect of retaining the host intestine in O-SBT in an altered O-SBT (AO-SBT) model. METHODS SBT was performed in a high-responder rat stain combination (blood group D Agouti --> Lewis). Immunosuppressive treatment consisting of a short course of FK506 (2 mg/kg/day IM for 3 days before transplantation and 0.3 mg/kg/day for 14 days after transplantation) was used. RESULTS Survival (mean +/- SD) of H-, O-, and AO-SBT untreated animals was 6.25+/-0.58 days, 6.5+/-0.58 days, and 6.7+/-0.25 days, respectively. With FK506 immunosuppression, survival of H-SBT animals was 49.3+/-13.17 days, whereas 75% (12/16) and 80% (4/5), respectively, of O-SBT and AO-SBT animals achieved indefinite survival (>120 days) with functioning grafts. CONCLUSION Our data suggest that heterotopic placement of intestinal allografts results in a more severe graft rejection than orthotopic placement. The indefinite survival of O-SBT is not due to of the removal of host intestine carrying a heavy load of gut-associated lymphoid tissue.

Small bowel allografts can either be placed heterotopically or orthotopically. In heterotopic small bowel transplantation (H-SBT), the host small intestine containing a substantial amount of gut-associated lymphoid tissue is removed, whereas in conventional orthotopic small bowel transplantation (O-SBT) it is retained. This study compared the allograft survival of H-SBT and O-SBT and evaluated the effect of retaining the host intestine in O-SBT in an altered O-SBT (AO-SBT) model.SBT was performed in a high-responder rat stain combination (blood group D Agouti --Lewis). Immunosuppressive treatment consisting of a short course of FK506 (2 mg/kg/day IM for 3 days before transplantation and 0.3 mg/kg/day for 14 days after transplantation) was used.Survival (mean +/- SD) of H-, O-, and AO-SBT untreated animals was 6.25+/-0.58 days, 6.5+/-0.58 days, and 6.7+/-0.25 days, respectively. With FK506 immunosuppression, survival of H-SBT animals was 49.3+/-13.17 days, whereas 75% (12/16) and 80% (4/5), respectively, of O-SBT and AO-SBT animals achieved indefinite survival (120 days) with functioning grafts.Our data suggest that heterotopic placement of intestinal allografts results in a more severe graft rejection than orthotopic placement. The indefinite survival of O-SBT is not due to of the removal of host intestine carrying a heavy load of gut-associated lymphoid tissue.

The 21 st Association for Cancer Immunotherapy (CIMT) Annual Meeting took place from May 15 th to May 17 th in Mainz, Germany, and was attended by a total of 855 academic and clinical professionals hailing from 33 different countries. The conference served as a platform for these experts to convene and discuss the latest breakthroughs in cancer immunology and immunotherapy research. Dedicated sessions covering advancements in artificial intelligence tools for cancer immunotherapy research, as well as the landscape of cancer care and cancer immunotherapy trials on the African continent, prompted lively and informative discussions among the attendees. This report aims to provide an overview of the most noteworthy highlights and key takeaways from CIMT2024.