An approach for long-term, multi-probe Neuropixels recordings in unrestrained rats

Abstract

The use of Neuropixels probes for chronic neural recordings in freely moving animals is not yet widespread. Stable chronic recording across months has been reported from a single brain area in rats, and probe re-use has been shown for mice after an implantation period of a few weeks. These initial studies raise three questions that need to be addressed for chronic recording from freely moving animals to become cost-effective and routine. First, how does long-term yield compare across different brain regions? Second, is it possible to achieve a cost-effective strategy for freely moving animals that is i) compact enough for multiple simultaneous probes to be implanted, ii) allows probe explantation and re-use, and, importantly, iii) is robust enough for stable multi-month recordings from rats (or other animals that can generate impact forces greater than those generated by mice)? Third, how does probe performance degrade after multiple cycles of implantation? Here we address these three questions, validating an approach for chronic Neuropixels recordings over a period of months, in freely moving rats performing a cognitively-demanding task. Daily recording sessions lasted up to five hours and required no human supervision. Our approach allows for implantation of multiple probes per rat and probe recovery at the end of the experiment. We found that, on average, hundreds of units can be recorded for multiple months. However, this long-term stability strongly depended on the dorsoventral and anteroposterior position in the brain, with greater stability in more anterior and ventral regions. Finally, we quantified degradation in the performance (input-referred noise) of explanted probes after each implantation and found this degradation to be insufficient to impair future single-unit recordings. We conclude that cost-effective, multi-region, and multi-probe Neuropixels recordings can be carried out with high yields over multiple months in rats or other similarly sized animals. Our methods and observations may facilitate the standardization of chronic recording from Neuropixels probes in freely moving animals.

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings

“…NP 2.0 probes are optimized for high-yield chronic implants in small mammals. To confirm the quality of NP 2.0 recording characteristics over at least 8 weeks, as done for NP 1.0 probes (Jun et al, 2017;Juavinett et al, 2019;Luo et al, 2020), we implanted NP 2.0 probes in rats and mice in 6 labs. Out of 21 subjects implanted across the 6 labs, 20 implants were successful and recorded neurons until the experiment was ended at the discretion of the experimenter (see Table 1 for details).…”

“…Recent advances such as the Neuropixels probe leveraged CMOS fabrication methods to significantly expand the number and density of recording sites (Jun et al, 2017;Raducanu et al, 2017), allowing unprecedented recordings of large populations of neurons distributed across the brain at single spike resolution (Allen et al, 2019;Siegle et al, 2019;Steinmetz et al, 2019;Stringer et al, 2019b). The Neuropixels probe has seen rapid adoption and wide application in diverse species including mice (Evans et al, 2018;Vélez-Fort et al, 2018;Bennett et al, 2019;Kostadinov et al, 2019;Musall et al, 2019;Park et al, 2019;Schröder et al, 2019;Stringer et al, 2019a;Liu et al, 2020;Sauerbrei et al, 2020), rats (Krupic et al, 2018;Gardner et al, 2019;Böhm and Lee, 2020;Luo et al, 2020), ferrets (Gaucher et al, 2020), and non-human primates (Trautmann et al, 2019). Nevertheless, key barriers still prevent the recording of individual neurons stably over long timescales of weeks to months, of large-scale activity in small animals that are freely behaving, and of neurons packed densely in brain structures with diverse geometries.…”

Accurate Localization of Linear Probe Electrode Arrays across Multiple Brains

“…This need is especially acute for recently developed Neuropixels probes . The probes are commercially available and have been rapidly adopted by many laboratories (Allen et al, 2019;Bennett et al, 2019;Böhm and Lee, 2020;Evans et al, 2018;Gardner et al, 2019;Kostadinov et al, 2019;Krupic et al, 2018;Luo et al, 2020;Musall et al, 2019;Sauerbrei et al, 2020;Siegle et al, 2021;Steinmetz et al, 2019;Trautmann et al, 2019). Neuropixels probes (Jun et al, 2017) (Steinmetz et al, 2021) provide recordings across 960 recording electrodes distributed over 9.6 mm shanks.…”

Improving scalability in systems neuroscience

“…Increasingly, modern neurotechnologies are being deployed chronically in implanted systems (Chiang et al, 2020;Schwarz et al, 2014;Tybrandt et al, 2018). The main concerns of chronic electrophysiological recordings are the unit yield, longevity, stability, and quality of neural signals (Juavinett et al, 2019;Luo et al, 2020). In all recording devices, the interfaces between the nervous system and a synthetic sensor ll involve innovations in advanced materials (Chen et al, 2017).…”