A unified open-source platform for multimodal neural recording and perturbation during naturalistic behavior

Abstract

Behavioral neuroscience faces two conflicting demands: long-duration recordings from large neural populations and unimpeded animal behavior. To meet this challenge, we developed ONIX, an open-source data acquisition system with high data throughput (2GB/sec) and low closed-loop latencies (<1ms) that uses a novel 0.3 mm thin tether to minimize behavioral impact. Head position and rotation are tracked in 3D and used to drive active commutation without torque measurements. ONIX can acquire from combinations of passive electrodes, Neuropixels probes, head-mounted microscopes, cameras, 3D-trackers, and other data sources. We used ONIX to perform uninterrupted, long (~7 hours) neural recordings in mice as they traversed complex 3-dimensional terrain. ONIX allowed exploration with similar mobility as non-implanted animals, in contrast to conventional tethered systems which restricted movement. By combining long recordings with full mobility, our technology will enable new progress on questions that require high-quality neural recordings during ethologically grounded behaviors.

Figure 1:. ONIX, a unified open-source platform for unencumbered freely moving recordings.

a, Simplified block diagram of the ONI (open neuro interface), illustrated via the tetrode headstage: multiple devices all communicate with the host PC over a single micro-coax cable via a serialization protocol, making it possible to design small multi-function headstages. b, The integrated inertial measurement unit and 3D-tracking redundantly measure animal rotation, which drives the motorized commutator without the need to measure tether torque. Small drive implants enable low-profile implants (~20 mm total height). c, The ONIX micro-coax, a 0.31 mm thin tether of up to 12 m length, compared to standard 12-wire digital tethers. d, Torque exerted on an animal’s head by tethers. Current tethers allow full mobility only in small arenas and in situations when the tether does not pull on the implant, while the ONIX micro-coax applies negligible torque. e, Performance of ONIX: With the 64 channel headstage, a 99.9% worst case closed-loop latency, from neural voltage reading, to host PC, and back to the headstage (e.g. to trigger an LED) of <1 ms can be achieved on Windows 10 (see also Suppl. Figs 6 & 7).

Figure 2:. Unrestricted naturalistic locomotion behavior with ONIX.

a, Overview of experiment: Mice were freely exploring a 3D arena made out of styrofoam pieces of varying heights. b, Unimplanted mice and mice with a standard tether (top) or ONIX micro coax (bottom) were tracked in 3d using multicamera markerless pose estimation. c, Head yaw and pitch occupancies over the course of a recording. Standard tethering significantly reduces freedom of head movement relative to unimplanted mice, whereas ONIX does not. d, Speed distributions over the course of a recording. Standard implants significantly reduce running speed, while ONIX results in only a modest speed reduction relative to unimplanted mice. e, 2D projection of mouse trajectories over the course of a recording session. ONIX retains the same spontaneous exploration behavior as unimplanted mice, while standard headstages and cables greatly reduce locomotion.

Figure 3:. Stable long-term recordings during naturalistic locomotion.

a, Position of one 3D-tracking sensor on the headstage during a 7.3 hour-long ONIX recording during which the mouse was free to explore the 3D arena. Red trace and excerpt show one of multiple instances of the mouse spontaneously jumping from a lower to a higher tile. b, Video frames of the jump (the tether is too thin to be visible at this magnification), see supplementary video 1. c, Raw voltages and spike peak amplitudes from the beginning (left) and end (right) of the recording. d, 3D-position, heading, and smoothed firing rate of entire recording. e, Same data as in d, for excerpt around jump. f, Z-position, raw voltage trace example, and sorted spikes from 71 neurons during the jump.

Figure 4:. ONIX is compatible with existing and future recording technologies.

a, ONIX, together with Bonsai, can simultaneously record from and synchronize multiple data sources, such as tetrode headstages, Neuropixels headstages, and/or UCLA Miniscopes. b, Top: a 64 channel extracellular headstage, as used in Figs. 1–3, with 3D-tracking, electrical stimulator, dual-channel LED driver, and IMU (bottom side; not shown). Bottom: example neural recording and corresponding 3D pose traces collected from the headstage. c, ONIX is compatible with existing UCLA Miniscopes (versions 3 and 4)^,. Middle: Maximum projection after background removal of an example recording in mouse CA1. Bottom: Background-corrected fluorescence traces (black) and CNMF output (via Minian, red) of 10 example neurons. d, An ONIX headstage for use with 2 Neuropixels probes, and IMU to enable torque-free commutator use for long-term freely behaving recordings. A voltage heat map shows a segment from a head-fixed recording. A voltage time-series from the channel indicated by the dotted line is shown in blue.