Accurate localization of linear probe electrodes across multiple brains

Abstract

Recently developed silicon probes have large numbers of recording electrodes on long linear shanks. Specifically, Neuropixels probes have 960 recording electrodes distributed over 9.6 mm shanks. Because of their length, Neuropixels probe recordings in rodents naturally span multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals have to be aligned to each other and to a standardized brain coordinate system. Here we report a workflow for accurate localization of individual electrodes in standardized coordinates and aligned across individual brains. This workflow relies on imaging brains with fluorescent probe tracks and warping 3-dimensional image stacks to standardized brain atlases. Electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed ground-truth experiments, in which motor cortex outputs are labelled with ChR2 and a fluorescence protein. Recording from brain regions targeted by these outputs reveals better than 100 µm accuracy for electrode localization.

Motor cortical output for skilled forelimb movement is selectively distributed across projection neuron classes

“…The imaged 3D brain volumes (v3D) were aligned to a standardized brain coordinate system (Allen Anatomical Template, AAT) using a semi-manual landmark-based method (big warp)(Bogovic et al, 2016). The v3Ds were additionally aligned to the template MRI image volume (MRI3D) acquired using fixed brains in the skull to further correct for any distortion due to extraction of the brain from the skull (Liu et al, 2020). Each probe track was manually marked on v3D fused with AAT, and the 3D coordinates of all electrode sites were finally determined on MRI3D using the mapping between AAT and MRI3D combined with the geometry of the Neuropixels probe.…”

Descending neocortical output critical for skilled forelimb movements is distributed across projection cell classes

“…The imaged 3D brain volumes (v3D) were aligned to a standardized brain coordinate system (Allen Anatomical Template, AAT) using a semi-manual landmark-based method (big warp) 85 . The v3Ds were additionally aligned to the template MRI image volume (MRI3D) acquired using fixed brains in the skull to further correct for any distortion due to extraction of the brain from the skull 86 . Each probe track was manually marked on v3D fused with AAT, and the 3D coordinates of all electrode sites were finally determined on MRI3D using the mapping between AAT and MRI3D combined with the geometry of the Neuropixels probe.…”

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

“…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.…”