The Hybrid Drive: a chronic implant device combining tetrode arrays with silicon probes for layer-resolved ensemble electrophysiology in freely moving mice

Abstract

Objective. Understanding the function of brain cortices requires simultaneous investigation at multiple spatial and temporal scales and to link neural activity to an animal's behavior. A major challenge is to measure within- and across-layer information in actively behaving animals, in particular in mice that have become a major species in neuroscience due to an extensive genetic toolkit. Here we describe the Hybrid Drive, a new chronic implant for mice that combines tetrode arrays to record within-layer information with silicon probes to simultaneously measure across-layer information. Approach. The design of our device combines up to 14 tetrodes and 2 silicon probes, that can be arranged in custom arrays to generate unique areas-specific (and multi-area) layouts. Main Results. We show that large numbers of neurons and layer-resolved local field potentials can be recorded from the same brain region across weeks without loss in electrophysiological signal quality. The drive's lightweight structure (~3.5 g) leaves animal behavior largely unchanged, compared to other tetrode drives, during a variety of experimental paradigms. We demonstrate how the data collected with the Hybrid Drive allow state-of-the-art analysis in a series of experiments linking the spiking activity of CA1 pyramidal layer neurons to the oscillatory activity across hippocampal layers. Significance. Our new device fits a gap in the existing technology and increases the range and precision of questions that can be addressed about neural computations in freely behaving mice.

Heterogeneity of network and coding states in CA1

“…We implanted 6 mice with the Hybrid Drive (Figure 1A; [28]), a novel recording device that combines linear silicon probes with high density tetrode arrays. Tetrodes were individually lowered to target pyramidal cell bodies in the stratum pyramidale of the CA1 region (Figure 1B,C) and enabled us to collect large ensemble activity of pyramidal neurons (up to ≈ 100) for up to 10 days.…”

“…As an important technical aside, here we recorded laminarly resolved LFP and neural ensembles are recorded from separate sites [28] (Figure 1), which avoids any spillovers of spiking activity in the LFP, which may bias LFP-spikes association measures. We then used a novel analytical procedure (Figure 4 and S3), derived from ref.…”

“…The fabrication of the Hybrid Drives and the implantation surgeries were done as described earlier [28]. In order to target the dorsal CA1 region of the hippcampus, a craniotomy was made over the right cortex (top-left corner at AP: -1.20 mm; ML: 0.6 mm relative to bregma; bottom-right corner at AP: -2.30 mm; ML: 2.10 mm relative to bregma) using a 0.9 Burr drill.…”

Direct Entorhinal Control of CA1 Temporal Coding

“…The fabrication of the Hybrid Drive was done as described earlier [19]. This version of the Hybrid Drive is equipped with a linear silicon probe, 13 tetrodes and an optic fiber was incorporated in the design to carry out in-vivo optogenetic manipulations.…”

State Dependent Coupling of Hippocampal Oscillations

“…Layer-resolved local field potential were extracted from the CA1 region of the dorsal hippocampus using multisite silicon probes (Fig 1B;Guardamagna et al, 2022). LFPs from SP, SR and SLM layers were used to extract signals in the following frequency bands: delta (1-5 Hz), theta (6-10 Hz), spindle (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), medium gamma (60-90 Hz) and fast gamma .…”