Optical inhibition of motor nerve and muscle activity

Introduction: There is no therapeutic approach that provides precise and rapidly reversible inhibition of motor nerve and muscle activity for treatment of spastic hypertonia. Methods: We used optogenetics to demonstrate precise and rapidly reversible light-mediated inhibition of motor nerve and muscle activity in vivo in transgenic Thy1::eNpHR2.0 mice. Results: We found optical inhibition of motor nerve and muscle activity to be effective at all muscle force amplitudes and determined that muscle activity can be modulated by changing light pulse duration and light power density. Conclusions: This demonstration of optical inhibition of motor nerves is an important advancement toward novel optogenetics-based therapies for spastic hypertonia.Stanford University (Stanford Bio-X Interdisciplinary Initiatives Award)Stanford University (National Institutes of Health Graduate Training Program in Biotechnology grant)W. M. Keck Foundation (grant)National Institutes of Health (U.S.) (NIH grant R01NS080954

Prescribing joint co-ordinates during model preparation in OpenSim improves lower limb unplanned sidestepping kinematics.

OBJECTIVES: Investigate how prescribing participant-specific joint co-ordinates during model preparation influences the measurement agreement of inverse kinematic (IK) derived unplanned sidestepping (UnSS) lower limb kinematics in OpenSim in comparison to an established direct kinematic (DK) model. DESIGN: Parallel forms repeatability. METHODS: The lower limb UnSS kinematics of 20 elite female athletes were calculated using: 1) an established DK model (criterion) and, 2) two IK models; one with (IKPC) and one without (IK0) participant-specific joint co-ordinates prescribed during the marker registration phase of model preparation in OpenSim. Time-varying kinematic analyses were performed using one dimensional (1D) statistical parametric mapping (α = 0.05), where zero dimensional (0D) Root Mean Squared Error (RMSE) estimates were calculated and used as a surrogate effect size estimates. RESULTS: Statistical differences were observed between the IKPC and DK derived kinematics as well as the IK0 and DK derived kinematics. For the IKPC and DK models, mean kinematic differences over stance for the three dimensional (3D) hip joint, 3D knee joint and ankle flexion/extension (F/E) degrees of freedom (DoF) were 46 ± 40% (RMSE = 5 ± 5°), 56 ± 31% (RMSE = 7 ± 4°) and 3% (RMSE = 2°) respectively. For the IK0 and DK models, mean kinematics differences over stance for the 3D hip joint, 3D knee joint and ankle F/E DoF were 70 ± 53% (RMSE = 14 ± 11°), 46 ± 48% (RMSE = 8 ± 7°) and 100% (RMSE = 11°) respectively. CONCLUSIONS: Prescribing participant-specific joint co-ordinates during model preparation improves the agreement of IK derived lower limb UnSS kinematics in OpenSim with an established DK model, as well as previously published in-vivo knee kinematic estimates

MOS 2.0: The Next Generation in Mission Operations Systems

A Mission Operations System (MOS) or Ground System constitutes that portion of an overall space mission Enterprise that resides here on Earth. Over the past two decades, technological innovations in computing and software technologies have allowed an MOS to support ever more complex missions while consuming a decreasing fraction of Project development budgets. Despite (or perhaps, because of) such successes, it is routine to hear concerns about the cost of MOS development. At the same time, demand continues for Ground Systems which will plan more spacecraft activities with fewer commanding errors, provide scientists and engineers with more autonomous functionality, process and manage larger and more complex data more quickly, all while requiring fewer people to develop, deploy, operate and maintain them. One successful approach to such concerns over this period is a multimission approach, based on the reuse of portions (most often software) developed and used in previous missions. The Advanced Multi-Mission Operations System (AMMOS), developed for deep-space science missions, is one successful example of such an approach. Like many computing-intensive systems, it has grown up in a near-organic fashion from a relatively simple set of tools into a complexly interrelated set of capabilities. Such systems, like a city lacking any concept of urban planning, can and will grow in ways that are neither efficient nor particularly easy to sustain. To meet the growing demands and unyielding constraints placed on ground systems, a new approach is necessary. Under the aegis of a multi-year effort to revitalize the AMMOS's multimission operations capabilities, we are utilizing modern practices in systems architecting and model-based engineering to create the next step in Ground Systems: MOS 2.0. In this paper we outline our work (ongoing and planned) to architect and design a multimission MOS 2.0, describe our goals and measureable objectives, and discuss some of the benefits that this top-down, architectural approach holds for creating a more flexible and capable MOS for Missions while holding the line on cost

Optogenetic Control of Targeted Peripheral Axons in Freely Moving Animals

<div><p>Optogenetic control of the peripheral nervous system (PNS) would enable novel studies of motor control, somatosensory transduction, and pain processing. Such control requires the development of methods to deliver opsins and light to targeted sub-populations of neurons within peripheral nerves. We report here methods to deliver opsins and light to targeted peripheral neurons and robust optogenetic modulation of motor neuron activity in freely moving, non-transgenic mammals. We show that intramuscular injection of adeno-associated virus serotype 6 enables expression of channelrhodopsin (ChR2) in motor neurons innervating the injected muscle. Illumination of nerves containing mixed populations of axons from these targeted neurons and from neurons innervating other muscles produces ChR2-mediated optogenetic activation restricted to the injected muscle. We demonstrate that an implanted optical nerve cuff is well-tolerated, delivers light to the sciatic nerve, and optically stimulates muscle in freely moving rats. These methods can be broadly applied to study PNS disorders and lay the groundwork for future therapeutic application of optogenetics.</p></div

Implantable optical nerve cuffs are well tolerated and activate MNs in anesthetized rats.

<p>(<i>A</i>) Biocompatible spiral cuffs were constructed from polydimethylsiloxane (PDMS) and covalently bound to a silicon-based optical fiber that was terminated with a stainless steel ferrule. (<i>B</i>) Optical nerve cuffs were implanted into rats around the sciatic nerve 4 weeks following AAV6:ChR2 delivery. (<i>C</i>) Typical traces of EMG (targeted and non-targeted muscles) and force (targeted muscle only) following illumination using the optical nerve cuff (20 mW, 5 ms, 1 Hz) in anesthetized rats 1 week following cuff implantation. (<i>D</i>) Representative force trace following a train of light pulses (20 mW, 2.5 ms, 36 Hz) using the nerve cuff. (<i>E</i>) Percentage of <i>smf</i> versus pulse width (20 mW light power) using direct laser light application (<i>n</i> = 7) or light transmitted through the implanted cuff (<i>n</i> = 3). (<i>F</i>) Percentage of <i>smf</i> versus light power (5 ms pulse width) using direct laser light application (<i>n</i> = 7) or light transmitted through the implanted cuff (<i>n</i> = 3). (<i>G</i>) Integrated EMG in targeted and non-targeted muscles following light delivery using the optical nerve cuff (20 mW, 5 ms) (<i>n</i> = 3). (<i>H</i>) Integrated EMG in the targeted muscle at 1 day, 1 week, and 1 month following implantation (<i>n</i> = 1). (<i>I</i>) Stride length of paws in age-matched wild-type littermates (<i>n</i> = 4) and rats 1 week post-implantation of optical nerve cuffs (<i>n</i> = 5).</p

Optogenetic activation of targeted sciatic nerve axons in awake and moving rats.

<p>(<i>A</i>) Optical nerve cuffs and EMG electrodes were implanted into rats 4 weeks following AAV6:ChR2 delivery. EMG electrodes were implanted onto the surface of the AAV6:ChR2-injected muscle (targeted) and onto the uninjected muscle on the opposite leg (contralateral). Non-anesthetized rats were tested for EMG activity on a treadmill 3 days following the surgery. (<i>B</i>) EMG activity in response to a pulse of blue light (20 mW, 5 ms) in the targeted and contralateral muscles in awake, non-moving rats. (<i>C</i>) EMG activity in response to pulses of light (20 mW, 5 ms, 1 Hz) in awake rats walking on a treadmill at constant speed (20 cm/s). (<i>D</i>) EMG activity in response to 150 ms trains of light (20 mW, 5 ms, 36 Hz) in awake rats walking on a treadmill. (<i>E</i>) Integrated EMG in the targeted muscle in response to optogenetic or physiological activation (<i>n</i> = 3, animals matched) for twitch and tetanus contractions. Integrated EMG responses following optogenetic activation are greater or equal to physiological activity (* <i>P</i><0.05; 2 tailed paired T-test). (<i>F</i>) Integrated EMG versus gait cycle demonstrating that activity was independent of the position of the legs (<i>n</i> = 32 trials, <i>R²</i> = 0.05).</p

Light-mediated muscle-specific activation of the sciatic nerve.

<p>(<i>A</i>) Blue light (473 nm) was applied to the sciatic nerve of anesthetized rats 4 weeks following injection of AAV6:ChR2 in the GN or TA. EMG plots show typical responses from optical stimulation taken with fine wire electrodes in the AAV6:ChR2 targeted-muscle (twitch trial: 20 mW, 5 ms, 1 Hz) (tetanus trial: 20 mW, 2.5 ms, 36 Hz). The distal tendon of the muscle was fixed to a transducer to measure force. Representative force traces are shown for corresponding optical activation and are scaled using supramaximal twitch force (<i>smf</i>). (<i>B</i>) Representative force traces in response to varying pulse widths of 20 mW blue light. (<i>C</i>) Percentage of <i>smf</i> versus pulse width (20 mW light power) for AAV6:ChR2 (<i>n</i> = 7, GN and TA animals combined) or wild-type (<i>n</i> = 3) rats. (<i>D</i>) Percentage of <i>smf</i> versus light power (5 ms pulse width). (<i>E</i>) Fine wire electrodes were placed in the targeted and non-targeted muscles of the sciatic nerve. Representative EMG traces are shown following electrical or optogenetic stimulation. (<i>F</i>) Integrated EMG versus pulse width (20 mW light power) in the targeted and non-targeted muscles following optical activation (<i>n</i> = 9, GN and TA animals combined).</p

Model Based Systems Engineering (MBSE) Applied to Radio Aurora Explorer (RAX) CubeSat Mission Operational Scenarios

Abstract—Small spacecraft are more highly resource-constrained by mass, power, volume, delivery timelines, and financial cost relative to their larger counterparts. Small spacecraft are operationally challenging because subsystem functions are coupled and constrained by the limited available commodities (e.g. data, energy, and access times to ground resources). Furthermore, additional operational complexities arise because small spacecraft components are physically integrated, which may yield thermal or radio frequency interference. In this paper, we extend our initial Model Based Systems Engineering (MBSE) framework developed for a small spacecraft mission by demonstrating the ability to model different behaviors and scenarios. We integrate several simulation tools to execute SysML-based behavior models, including subsystem functions and interna

Jet Propulsion

in modeling and systems engineering. MBSE uses Systems Modeling Language (SysML) as its modeling language. SysML is a domain-specific modeling language for systems engineering used to specify, analyze, design, optimize, and verify systems

Early Formulation Model-centric Engineering on Nasa's Europa Mission Concept Study

By leveraging the existing Model-Based Systems Engineering (MBSE) infrastructure at JPL and adding a modest investment, the Europa Mission Concept Study made striking advances in mission concept capture and analysis. This effort has reaffirmed the importance of architecting and successfully harnessed the synergistic relationship of system modeling to mission architecting. It clearly demonstrated that MBSE can provide greater agility than traditional systems engineering methods. This paper will describe the successful application of MBSE in the dynamic environment of early mission formulation, the significant results produced and lessons learned in the process