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Understanding how internal states like satiety are connected to animal behavior is a fundamental question in neuroscience.Hydra vulgaris, a freshwater cnidarian with only eleven neuronal cell types, serves as a tractable model system for studying state-dependent behaviors. We find that starvedHydraconsistently moves toward light, while fedHydrado not. By modeling this behavior as a set of three sequences - head orientation, jump distance, and jump rate -we demonstrate that the satiety state only affects the rate of the animal jumping to a new position, while the orientation and jump distance are unaffected. These findings yield insights into how internal states in a simple organism,Hydra, affect specific elements of a behavior, and offer general principles for studying the relationship between state-dependent behaviors and their underlying molecular mechanisms.

Funder: NIH U18EB029353, NSF GRFP, Funder: NIH U18EB029353, Funder: NIH R01DE021798, NSF GRFP, Funder: NIH R01DE021798, Implantable bioelectronic devices for the simulation of peripheral nerves could be used to treat disorders that are resistant to traditional pharmacological therapies. However, for many nerve targets, this requires invasive surgeries and the implantation of bulky devices (about a few centimetres in at least one dimension). Here we report the design and in vivo proof-of-concept testing of an endovascular wireless and battery-free millimetric implant for the stimulation of specific peripheral nerves that are difficult to reach via traditional surgeries. The device can be delivered through a percutaneous catheter and leverages magnetoelectric materials to receive data and power through tissue via a digitally programmable 1 mm × 0.8 mm system-on-a-chip. Implantation of the device directly on top of the sciatic nerve in rats and near a femoral artery in pigs (with a stimulation lead introduced into a blood vessel through a catheter) allowed for wireless stimulation of the animals' sciatic and femoral nerves. Minimally invasive magnetoelectric implants may allow for the stimulation of nerves without the need for open surgery or the implantation of battery-powered pulse generators.

The simple and compact optics of lensless microscopes and the associated computational algorithms allow for large fields of view and the refocusing of the captured images. However, existing lensless techniques cannot accurately reconstruct the typical low-contrast images of optically dense biological tissue. Here we show that lensless imaging of tissue in vivo can be achieved via an optical phase mask designed to create a point spread function consisting of high-contrast contours with a broad spectrum of spatial frequencies. We built a prototype lensless microscope incorporating the ‘contour’ phase mask and used it to image calcium dynamics in the cortex of live mice (over a field of view of about 16 mm2) and in freely moving Hydra vulgaris, as well as microvasculature in the oral mucosa of volunteers. The low cost, small form factor and computational refocusing capability of in vivo lensless microscopy may open it up to clinical uses, especially for imaging difficult-to-reach areas of the body.

Understanding how neural circuits are regenerated following injury is a fundamental question in neuroscience.Hydrais a powerful model for studying this process because it has significant and reproducible regenerative abilities, a simple and transparent body that allows for whole nervous system imaging, and established methods for creating transgenics with cell-type-specific expression. In addition, cnidarians such asHydrasplit from bilaterians (the group that encompasses most model organisms used in neuroscience) over 500 million years ago, so similarities with other models likely indicates deeply conserved biological processes.Hydrais a long-standing regeneration model and is an emerging model for neuroscience; however, relatively little is known regarding the restoration of neural activity and behavior following significant injury. In this study, we ask if regenerating neurons reach a terminal cell fate and then reform functional neural circuits, or if neural circuits regenerate first and then guide the constituent cells toward their terminal fate. To address this question, we developed a dual-expression transgenicHydraline that expresses a cell-type-specific red fluorescent protein (tdTomato) in ec5 peduncle neurons, and a calcium indicator (GCaMP7s) in all neurons. This transgenic line allowed us to monitor neural activity while we simultaneously track the reappearance of terminally differentiated ec5 neurons as determined by the expression of tdTomato. Using SCAPE (Swept Confocally Aligned Planar Excitation) microscopy, we tracked both calcium activity and expression of tdTomato-positive neurons in 3D with single-cell resolution during regeneration ofHydra’saboral end. We observed tdTomato expression in ec5 neurons approximately four hours before the neural activity begins to display synchronized patterns associated with a regenerated neural circuit. These data suggest that regenerating neurons undergo terminal differentiation prior to re-establishing their functional role in the nervous system. The combination of dynamic imaging of neural activity and gene expression during regeneration makeHydraa powerful model system for understanding the key molecular and functional processes involved in neuro-regeneration following injury.

Intercellular calcium waves (ICW) are complex signaling phenomena that control many essential biological activities, including smooth muscle contraction, vesicle secretion, gene expression, and changes in neuronal excitability. Accordingly, the remote stimulation of ICW may result in versatile new biomodulation and therapeutic strategies. Here, we demonstrate that light-activated molecular machines (MM), molecules that rotate and perform mechanical work on the molecular scale, can remotely stimulate ICW. Live-cell calcium tracking and pharmacological experiments reveal that MM-induced ICW are driven by the activation of inositol triphosphate (IP3) mediated signaling pathways by unidirectional, fast-rotating MM. We then demonstrated that MM-induced ICW can be used to control muscle contractionin vitroin cardiomyocytes and animal behaviorin vivoinHydra vulgaris. Consequentially, this work demonstrates a new strategy for the direct control of cell signaling and downstream biological function using molecular-scale devices.

Fabricating inorganic materials with designed three-dimensional nanostructures is an exciting yet challenging area of research and industrial application. Here, we develop an approach to 3D print high-quality nanostructures of silica with sub-200 nm resolution and with the flexible capability of rare-earth element doping. The printed SiO2 can be either amorphous glass or polycrystalline cristobalite controlled by the sintering process. The 3D-printed nanostructures demonstrate attractive optical properties. For instance, the fabricated micro-toroid optical resonators can reach quality factors (Q) of over 104. Moreover, and importantly for optical applications, doping and codoping of rare-earth salts such as Er3+, Tm3+, Yb3+, Eu3+ and Nd3+ can be directly implemented in the printed SiO2 structures, showing strong photoluminescence at the desired wavelengths. This technique shows the potential for building integrated microphotonics with silica via 3D printing. A 3D-printing technique has been developed to create high-quality pure silica nanostructures with sub-200 nm resolution and the flexible capability of rare-earth element doping. It shows excellent application potential in three-dimensional micro- and nanophotonics.

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Electrical neural interfaces serve as direct communication pathways that connect the nervous system with the external world. Technological advances in this domain are providing increasingly more powerful tools to study, restore, and augment neural functions. Yet, the complexities of the nervous system give rise to substantial challenges in the design, fabrication, and system-level integration of these functional devices. In this review, we present snapshots of the latest progresses in electrical neural interfaces, with an emphasis on advances that expand the spatiotemporal resolution and extent of mapping and manipulating brain circuits. We include discussions of large-scale, long-lasting neural recording; wireless, miniaturized implants; signal transmission, amplification, and processing; as well as the integration of interfaces with optical modalities. We outline the background and rationale of these developments and share insights into the future directions and new opportunities they enable.

Magnetoelectric materials convert magnetic fields to electric fields and have applications in wireless data and power transmission, electronics, sensing, data storage, and biomedical technology. For example, magnetoelectrics could enable precisely timed remote stimulation of neural tissue, but the resonance frequencies where magnetoelectric effects are maximized are typically too high to stimulate neural activity. To overcome this challenge, we created the first self-rectifying magnetoelectric “metamaterial.” This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. This “self-rectification” allows us to generate arbitrary electrical pulse sequences that have a time-averaged voltage in excess of 1 V. As a result, we can use magnetoelectric nonlinear metamaterials (MNMs) to remotely stimulate peripheral nerves with repeatable latencies of less than 5 ms, which is more than 120 times faster than previous neural stimulation approaches based on magnetic materials. These short latencies enable this metamaterial to be used in applications where fast neural signal transduction is necessary such as in sensory or motor neuroprosthetics. As a proof of principle, we show wireless stimulation to restore a sensory reflex in an anesthetized rat model as well as using the MNM to restore signal propagation in a severed nerve. The rational design of nonlinearities in the magnetic-to-electric transduction pathway as described here opens the door to many potential designs of MNMs tailored to applications spanning electronics, biotechnology, and sensing.

Here we show how photonic microring resonators enable real-time detection of Nitric Oxide (NO) in vivo, which is critical for physiological monitoring particularly during the wound healing process.

This article presents a hardware platform including stimulating implants wirelessly powered and controlled by a shared transmitter (TX) for coordinated leadless multisite stimulation. The adopted novel single-TX, multiple-implant structure can flexibly deploy stimuli, improve system efficiency, easily scale stimulating channel quantity, and relieve efforts in device synchronization. In the proposed system, a wireless link leveraging magnetoelectric (ME) effect is co-designed with a robust and efficient system-on-chip (SoC) to enable reliable operation and individual programming of every implant. Each implant integrates a 0.8-mm2 chip, a 6-mm2 ME film, and an energy storage capacitor within a 6.2-mm3 size. ME power transfer is capable of safely transmitting milliwatt power to devices placed several centimeters away from the TX coil, maintaining good efficiency with size constraints, and tolerating 60 degree, 1.5-cm misalignment in angular and lateral movement. The SoC robustly operates with 2-V source amplitude variations that spans a 40-mm TX-implant distance change, realizes individual addressability through physical unclonable function (PUF) IDs, and achieves 90% efficiency for 1.5-3.5-V stimulation with fully programmable stimulation parameters., Comment: This paper has been published in IEEE Journal of Solid-State Circuits, 2021

ImportanceThe outbreak of Coronavirus diseases 2019 (COVID-19) disease has increased demand for N95 respirators, surgical masks, and other facial coverings to stop the spread of SARS-CoV-2. Research shows that N95 respirators perform the best at filtering viral droplets and aerosols, however these masks are much more difficult to manufacture and expensive to distribute on a large scale, which led to shortages during the pandemic. Surgical masks, on the other hand, were more widely available and have been previously used to mitigate the spread of tuberculosis and influenza.ObjectivesTo evaluate the filter filtration efficiency (FFE) of three elastomeric harness designs in hospital and research settings in order to improve facemask seal.Design, setting and participantsA multi-institutional collaboration between engineers and health professionals, conducted between November 2020 and March 2021, was set up to design an elastomeric harness to improve the face seal of a surgical mask. Three elastomeric harness designs were created with harness designs 1 and 2 tested in a research laboratory setting and harness design 2.1 tested in a hospital setting. The initial harness design 1 was laser cut for testing and design 2 was developed to improve the detected particle leakage around the nose bridge area by introducing more material in that region. Design 2.1 is developed for hospital settings with less material around the nose bridge to reduce vision disruption. The designs were tested on mannequins and human volunteers using IR imaging and standard fit testing equipment.Main Outcomes and MeasuresOur elastomeric harness can improve the seal of a surgical mask allowing it to pass the fit test used to evaluate N95 respirators. 24/39 participants achieved a passing score of 100 or more while wearing the second harness design. IR imaging determined that the nasal sidewalls region of the mask is most prone to leakage when using our first elastomeric harness.Conclusions and RelevanceOverall, these results confirm that elastomeric harnesses combined with surgical masks improve their ability to filter aerosolized particles, which is especially important when in close proximity to individuals who are infectious or while performing aerosol-generating medical procedures.

Designing implantable bioelectronic systems that continuously monitor physiological functions and simultaneously provide personalized therapeutic solutions for patients remains a persistent challenge across many applications ranging from neural systems to bioelectronic organs. Closed-loop systems typically consist of three functional blocks, namely, sensors, signal processors and actuators. An effective system, that can provide the necessary therapeutics, tailored to individual physiological factors requires a distributed network of sensors and actuators. While significant progress has been made, closed-loop systems still face many challenges before they can truly be considered as long-term solutions for many diseases. In this review, we consider three important criteria where materials play a critical role to enable implantable closed-loop systems: Specificity, Biocompatibility and Connectivity. We look at the progress made in each of these fields with respect to a specific application and outline the challenges in creating bioelectronic technologies for the future.

Advances in sensing technology raise the possibility of creating neural interfaces that can more effectively restore or repair neural function and reveal fundamental properties of neural information processing. To realize the potential of these bioelectronic devices, it is necessary to understand the capabilities of emerging technologies and identify the best strategies to translate these technologies into products and therapies that will improve the lives of patients with neurological and other disorders. Here, we discuss emerging technologies for sensing brain activity, anticipated challenges for translation, and perspectives for how to best transition these technologies from academic research labs to useful products for neuroscience researchers and human patients.

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle. This will involve fabrication with existing yet nontraditional materials and procedures. We further emphasize the need to advance materials for improved flexible electrodes as an essential advance to record from neurons in brainstem and spinal cord in moving animals.