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  1. Abstract Vagus nerve stimulation has shown many benefits for disease therapies but current approaches involve imprecise electrical stimulation that gives rise to off-target effects, while the functionally relevant pathways remain poorly understood. One method to overcome these limitations is the use of optogenetic techniques, which facilitate targeted neural communication with light-sensitive actuators (opsins) and can be targeted to organs of interest based on the location of viral delivery. Here, we tested whether retrograde adeno-associated virus (rAAV2-retro) injected in the heart can be used to selectively express opsins in vagus nerve fibers controlling cardiac function. Furthermore, we investigated whether perturbations in cardiac function could be achieved with photostimulation at the cervical vagus nerve. Viral injection in the heart resulted in robust, primarily afferent, opsin reporter expression in the vagus nerve, nodose ganglion, and brainstem. Photostimulation using both one-photon stimulation and two-photon holography with a GRIN-lens incorporated nerve cuff, was tested on the pilot-cohort of injected mice. Changes in heart rate, surface electrocardiogram, and respiratory responses were observed in response to both one- and two-photon photostimulation. The results demonstrate feasibility of retrograde labeling for organ targeted optical neuromodulation.
  2. Current designs of powered prosthetic limbs are limited by the nearly exclusive use of DC motor technology. Soft actuators promise new design freedom to create prosthetic limbs which more closely mimic intact neuromuscular systems and improve the capabilities of prosthetic users. This work evaluates the performance of a hydraulically amplified self-healing electrostatic (HASEL) soft actuator for use in a prosthetic hand. We compare a linearly-contracting HASEL actuator, termed a Peano-HASEL, to an existing actuator (DC motor) when driving a prosthetic finger like those utilized in multi-functional prosthetic hands. A kinematic model of the prosthetic finger is developed and validated, and is used to customize a prosthetic finger that is tuned to complement the force-strain characteristics of the Peano-HASEL actuators. An analytical model is used to inform the design of an improved Peano-HASEL actuator with the goal of increasing the fingertip pinch force of the prosthetic finger. When compared to a weight-matched DC motor actuator, the Peano-HASEL and custom finger is 10.6 times faster, has 11.1 times higher bandwidth, and consumes 8.7 times less electrical energy to grasp. It reaches 91% of the maximum range of motion of the original finger. However, the DC motor actuator produces 10 times the fingertipmore »force at a relevant grip position. In this body of work, we present ways to further increase the force output of the Peano-HASEL driven prosthetic finger system, and discuss the significance of the unique properties of Peano-HASELs when applied to the field of upper-limb prosthetic design. This approach toward clinically-relevant actuator performance paired with a substantially different form-factor compared to DC motors presents new opportunities to advance the field of prosthetic limb design.« less