ONIX: A Neural Acquisition System for Unencumbered, Closed-Loop Recordings in Small, Freely Moving Animals

PROJECT SUMMARY Over the last century, extracellular recording technologies have progressed from handmade needle electrodes and vacuum tube amplifiers to microfabricated devices containing hundreds of recording sites and on-chip digitization circuits. This technological arc has facilitated Nobel-prize winning discoveries such as the unitary nature of action potentials, the computations underlying mammalian vision, and the neural basis of spatial learning, among many other notable findings. To study increasingly sophisticated aspects of brain function, technical development has been driven by two competing goals: (1) permitting high-fidelity communication with as many neurons as possible and (2) minimizing the impact of recordings on normal animal behavior. While great progress has been made on the first goal, there is growing recognition that increased effort must be allotted to reduce the behavioral burden of neural implants, especially in mice. Toward this end, Open Ephys Inc. proposes to create ONIX, a high-performance neural recording ecosystem that permits unencumbered mouse behavior for arbitrarily long recording sessions in large, complex environments. A key component of ONIX will be head-mounted devices that measure their own position and orientation. This information is sent to a low-cost, easy-to-install cable robot that keeps the ONIX ultra-light tether approximately vertical at all times while compensating for tether induced head torque. This enables, for the first time, recordings during unencumbered naturalistic mouse behavior. Further, using advanced digital circuitry, ONIX will be probe-agnostic and capable of working with all modern recording devices, including Intan chips, Neuropixels, and miniature endoscopes for calcium imaging. ONIX will seamlessly integrate into existing, widely used software such as the Open Ephys GUI, Bonsai, and DeepLabCut Live for maximum market penetration without requiring labs to learn new tools or modify acquisition workflows. In summary, ONIX will provide high-bandwidth, closed-loop performance without burdening mice in room-scale 3D environments. In combination with other innovative tools for rich, quantitative measurement of animal behavior, ONIX will accelerate the field towards a golden age of quantitative neuroethology.