PROJECT SUMMARY FINAL – U41 Supplement Despite a wide-ranging interest in performing clinical research for bioelectronic medicine applications, there are no available open-architecture and open-source implantable systems for autonomic nerve stimulation and recording. As a result, clinical researchers face significant technical, regulatory, and financial hurdles in getting access to the implantable neuromodulation technologies that are required for performing these clinical studies. There are several clinical closed-loop implantable neuromodulation systems presently available and they have been helpful in supporting clinical research. However, in their current form, none are suitable for the bioelectronic medicine applications, as they lack key functional modules for accessing the autonomic nerves; moreover, many of them use closed architectures (e.g., the use of custom ASICs instead of commercial over-the-shelf components) and proprietary software. Therefore, the overall objective of this HORNET Center for Autonomic Nerve Recording and Stimulation Systems (CARSS) is to develop an open-architecture and open-source implantable system for autonomic nerve stimulation and recording. In this administrative supplement, we will perform short and long term validation of functionality and safety of system components in large and small animal models. The CARSS system includes an external charger and controller, implantable pulse generator, and an assortment of interoperable and implantable leads for stimulation and sensing. The stomach and duodenum were selected for long term validation, consistent with the focus of the NIH SPARC program. We will test in pig the implantable pulse generator, vagal nerve and sacral nerve stimulation leads, electrocardiographic (ECG) leads, electromyographic (EMG) leads, and accelerometer-based motion sensing (AMS) leads. Our remaining leads, including the helical cuff targeting nerves less than 1 mm in diameter, mechanical sensing leads, and electrochemical sensors, will be tested in rats acutely and then chronically. The electronics module for the CARSS system will be connected externally to the leads to perform stimulation and sensing.