10 June 2021 - Research

Another week, another Nature Protocols paper! The Haesler and Kloosterman labs, in collaboration with ATLAS Neuroengineering, describe how to implant Neuropixels probes for chronic recording of neuronal activity in freely behaving animals.

Two months after introducing Neuropixels 2.0 in Science, NERF researchers have published a detailed step-by-step protocol on how to implant the probes for chronic recordings using specially designed fixtures.

"Most Neuropixels users today perform acute recordings in head-restrained animals and insert one or multiple probes into the same brain on a given experimental day," says Sebastian Haesler. "In this way, scientists can record several hundreds of neurons in multiple brain regions simultaneously, but that approach still has important limitations."

Chronic recording in freely moving animals

If we want to gain a better understanding of how the complex network of neurons in the brain coordinates our behaviors and activities, we need to be able to measure neuronal activity during such behavior.

"We not only need to measure neuronal activity in a lot of cells or brain regions at once, but we need to do so in awake, behaving animals, in other words: animals that can move freely, and over much longer periods of time," says Cagatay Aydin, a postdoctoral scientist in the Haesler lab who has used Neuropixels to record from more than 6000 sites at once.

This allows scientists like Haesler and Kloosterman to study for example, learning and memory over time, or how brain disorders progress.

3D-printed fixtures

It's precisely for this reason that scientists from the Haesler and Kloosterman lab teamed up with ATLAS Neuroengineering to develop compact and reusable 3D-printed fixtures for implantation of Neuropixels probes.

"The fixtures consist of two parts: a covered main body and a skull connector," explains Rik van Daal, a PhD student in the Kloosterman lab and KU Leuven ESAT-MNS. "We have single-, dual- and movable-probe fixture variants, in a design aimed to balance dimensions, weight and robustness."

Implantation Fixtures
Single-probe (left) and dual-probe (right) fixture variant for chronic Neuropixels probe implantation

The new Nature Protocols paper details all the steps, from assembly and implantation to probe retrieval after completing an experiment. Frédéric Michon, postdoc in the Kloosterman lab: "Because the probes can be safely recovered for later reimplantation, the set up is very cost-effective and can in some cases replace additional acute preparations."

"We are excited to share this protocol for routine chronic recording with Neuropixels probes with the world," adds Fabian Kloosterman. "Our approach increases both the throughput and reliability of in vivo neurophysiology experiments, so we hope it will helpful for many other researchers."

Implantation of Neuropixels probes for chronic recording of neuronal activity in freely behaving mice and rats.
van Daal, Aydin, Michon et al. Nature Protocols 2021

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