Chronic, Reusable, Multiday Neuropixels Recordings during Free-Moving Operant Behavior

Abstract

Electrophysiological recording is a powerful technique to examine neuronal substrates underlying cognition and behavior. Neuropixels probes provide a unique capacity to capture neuronal activity across many brain areas with high spatiotemporal resolution. Neuropixels are also expensive and optimized for acute, head-fixed use, both of which limit the types of behaviors and manipulations that can be studied. Recent advances have addressed the cost issue by showing chronic implant, explant, and reuse of Neuropixels probes, but the methods were not optimized for use in free-moving behavior. There were specific needs for improvement in cabling/connection stability. Here, we extend that work to demonstrate chronic Neuropixels recording, explant, and reuse in a rat model during fully free-moving operant behavior. Similar to prior approaches, we house the probe and headstage within a 3D-printed housing that avoids direct fixation of the probe to the skull, enabling eventual explant. We demonstrate innovations to allow chronic headstage connection with protection against environmental factors and a more stable cabling setup to reduce the tension that can interrupt recording. We demonstrate this approach with rats performing two different behavioral tasks, in each case showing: (1) chronic single- or dual-probe recordings in free-moving rats in operant chambers and (2) reusability of Neuropixels 1.0 probes with continued good single-unit yield after retrieval and reimplant. We thus demonstrate the potential for Neuropixels recordings in a wider range of species and preparations.

An adaptable, reusable, and light implant for chronic Neuropixels probes

“…These probes allow experimenters to produce brain-wide maps of neural activity in head-restrained mice using acute recordings (Allen et al, 2019; International Brain Laboratory et al, 2023; Steinmetz et al, 2019; Stringer et al, 2019). To track neurons across days, and to use freely moving animals, the probes can be implanted chronically, with procedures that are permanent (Jun et al, 2017; Steinmetz et al, 2021) or recoverable (Ghestem et al, 2023; Juavinett et al, 2019; Luo et al, 2020; Song et al, 2024; Steinmetz et al, 2021; van Daal et al, 2021; Vöröslakos et al, 2021). Permanent implants are lightweight and stable, but their use at scale is not financially feasible.…”

The flow of reward information through neuronal ensembles in the accumbens

“…27 Likewise, our correlation matrix leverages data from multiple sessions and rats, capturing the strength of “functional” connections related to task events in a kind of “meta-brain” of 17 animals performing the same behavioral task, and thus, it lacks individual-level detail because of restrictions imposed by current recording methods. Notably, even recent advancements like Neuropixels are primarily optimized for head-fixed setups, 37,47,49 but see 71 . We need novel high-density electrode technologies for freely moving rodents to record more neurons simultaneously within a single brain, unlocking a deeper understanding of individual neural dynamics under more naturalistic conditions than those provided by head-fixed setups.…”