The DMCdrive: practical 3D-printable micro-drive system for reliable chronic multi-tetrode recording and optogenetic application in freely behaving rodents

Abstract

Electrophysiological recording and optogenetic control of neuronal activity in behaving animals have been integral to the elucidation of how neurons and circuits modulate network activity in the encoding and causation of behavior. However, most current electrophysiological methods require substantial economical investments and prior expertise. Further, the inclusion of optogenetics with electrophysiological recordings in freely moving animals remains a general challenge. Expansion of the technological repertoire across laboratories, research institutes, and countries, demands open access to high-quality devices that can be built with little or no prior expertise from easily accessible parts of low cost. We here present a very affordable, truly easy-to-assemble micro-drive for electrophysiology in combination with optogenetics in freely moving mice and rats. The DMCdrive is particularly suited for reliable long-term recordings of neurons and network activities, and simplify optical tagging and manipulation of neurons in the recorded brain region. The highly functional and practical drive design has been optimized for accurate tetrode movement in brain tissue, and remarkably reduced build time. We provide a complete overview of the drive design, its assembly and use, and proof-of-principle demonstration of long-term recordings paired with cell-type-specific optogenetic manipulations in the prefrontal cortex (PFC) of freely moving transgenic mice and rats.

Mesotrode: chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice

“…The recording site of each tetrode is confirmed using post-hoc histological analysis (Figure 1D). We found that the single unit activity was relatively stable during one week, two weeks, and two months of recordings after implantation (Figure 1F, G), which is consistent with previously reported chronic tetrode recordings in mice (Tolias et al, 2007;Hong and Lieber, 2019;Kim, Brünner and Carlén, 2020;Voigts et al, 2020).…”

Mesotrode allows chronic simultaneous mesoscale cortical imaging and subcortical or peripheral nerve spiking activity recording in mice

“…The recording site of each tetrode is confirmed using post-hoc histological analysis (Figure 1D). We found that the single unit activity was relatively stable during one week, two weeks, and two months of recordings after implantation (Figure 1F, G), which is consistent with previously reported chronic tetrode recordings in mice (Tolias et al, 2007;Hong and Lieber, 2019;Kim, Brünner and Carlén, 2020;Voigts et al, 2020). We implanted a total of 29 tetrodes in the midbrain, hippocampus, thalamus, striatum, and cortex of 14 mice, and recorded the activity of 110 neurons with simultaneous mesoscale cortical imaging for up to 2 months after implantation (Figure 2).…”

Network asynchrony underlying increased broadband gamma power

“…PV-Cre mice were used as controls. To allow for lightactivation and identification of the activity of mPFC PV interneurons in the electrophysiological recordings (opto-tagging; Kim et al, 2016Kim et al, , 2020, an adeno-associated virus (AAV) vector with Credependent expression of channelrhodopsin-2 (ChR2) fused to mCherry (AAV-DIO-ChR2-mCherry) was unilaterally targeted to the mPFC (Cardin et al, 2009) (PV-Cre/NR1f/f, n = 3, PV-Cre, n = 4; Figs.…”

“…As our LFP analyses indicated increased neuronal firing and altered state transitions in mice lacking NMDAR activity in PV neurons, our next investigations focused on single unit activities during DOWN to UP transitions. As before (Kim et al, 2016(Kim et al, , 2020, we used opto-tagging to identify the activity of PV interneurons in PV-Cre and PV-Cre/NR1f/f mice injected with AAV-DIO-ChR2-mCherry (Figs.…”