The authors would like to thank Angela Gomez Fonseca for the inspiration to develop the drive and all the students who ran pilot experiments with the animals, Milan Bogers, Floor van Ravenswoud, and Eva Severijnen. This work was supported by the Dutch Research Council (NWO; Crossover Program 17619 &#34;INTENSE&#34;).

Open&#45;Source Implant for Multi&#45;Region Electrophysiological Monitoring in Rats

<ol>
	<li>Deffieux, T., Demen&#233;, C., Tanter, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+Ultrasound+Imaging:+A+New+Imaging+Modality+for+Neuroscience.">Functional Ultrasound Imaging: A New Imaging Modality for Neuroscience.</a> Neuroscience. 474, 110-121 (2021).</li><li>Finn, E. S., Poldrack, R. A., Shine, J. 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D., Contero, M., Company, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parametric+CAD+modeling:+An+analysis+of+strategies+for+design+reusability.">Parametric CAD modeling: An analysis of strategies for design reusability.</a> Comput Aided Des. 74, 18-31 (2016).</li><li>Kloosterman, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Micro-drive+array+for+chronic+in+vivo+recording:+Drive+fabrication.">Micro-drive array for chronic in vivo recording: Drive fabrication.</a> J Vis Exp. (26), e1094 (2009).</li><li>Voigts, J., Siegle, J. H., Pritchett, D. L., Moore, C. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+flexDrive:+An+ultra-light+implant+for+optical+control+and+highly+parallel+chronic+recording+of+neuronal+ensembles+in+freely+moving+mice.">The flexDrive: An ultra-light implant for optical control and highly parallel chronic recording of neuronal ensembles in freely moving mice.</a> Front Syst Neurosci. 7, (2013).</li><li>Voigts, J., Newman, J. P., Wilson, M. A., Harnett, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+easy-to-assemble,+robust,+and+lightweight+drive+implant+for+chronic+tetrode+recordings+in+freely+moving+animals.">An easy-to-assemble, robust, and lightweight drive implant for chronic tetrode recordings in freely moving animals.</a> J Neural Eng. 17 (2), 026044 (2020).</li><li>Sheng, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+novel+3D-printed+multi-driven+system+for+large-scale+neurophysiological+recordings+in+multiple+brain+regions.">A novel 3D-printed multi-driven system for large-scale neurophysiological recordings in multiple brain regions.</a> J Neurosci Methods. 361, 109286 (2021).</li><li>V&#246;r&#246;slakos, M., Petersen, P. C., V&#246;r&#246;slakos, B., Buzs&#225;ki, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metal+microdrive+and+head+cap+system+for+silicon+probe+recovery+in+freely+moving+rodent.">Metal microdrive and head cap system for silicon probe recovery in freely moving rodent.</a> eLife. 10, e65859 (2021).</li><li>Mishra, A., Marzban, N., Cohen, M. X., Englitz, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamics+of+neural+microstates+in+the+VTA-striatal-prefrontal+loop+during+novelty+exploration+in+the+rat.">Dynamics of neural microstates in the VTA-striatal-prefrontal loop during novelty exploration in the rat.</a> bioRxiv. , (2020).</li><li>Allen, L. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=RatHat:+A+self-targeting+printable+brain+implant+system.">RatHat: A self-targeting printable brain implant system.</a> eNeuro. 7 (2), (2020).</li><li>. Soldering Safety Available from: <a target="_blank" href="https://safety.eng.cam.ac.uk/safe-working/copy_of_soldering-safety">https://safety.eng.cam.ac.uk/safe-working/copy_of_soldering-safety</a> (2018)</li><li>. Harvard Soldering Safety Guidelines Available from: <a target="_blank" href="https://www.ehs.harvard.edu/sites/default/files/soldering_safety_guidelines.pdf">https://www.ehs.harvard.edu/sites/default/files/soldering_safety_guidelines.pdf</a> (2019)</li><li>Samanta, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=CBD+lengthens+sleep+but+shortens+ripples+and+leads+to+intact+simple+but+worse+cumulative+memory.">CBD lengthens sleep but shortens ripples and leads to intact simple but worse cumulative memory.</a> iScience. 26 (11), 108327 (2023).</li><li>Machado, F., Malpica, N., Borromeo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Parametric+CAD+modeling+for+open+source+scientific+hardware:+Comparing+OpenSCAD+and+FreeCAD+Python+scripts.">Parametric CAD modeling for open source scientific hardware: Comparing OpenSCAD and FreeCAD Python scripts.</a> PLOS One. 14 (12), e0225795 (2019).</li><li>Schwarz, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+head-fixed+behaving+rat:+Procedures+and+pitfalls.">The head-fixed behaving rat: Procedures and pitfalls.</a> Somatosens Mot Res. 27 (4), 131-148 (2010).</li><li>Gardiner, T. W., Toth, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereotactic+surgery+and+long-term+maintenance+of+cranial+implants+in+research+animals.">Stereotactic surgery and long-term maintenance of cranial implants in research animals.</a> Contemp Top Lab Anim Sci. 38 (1), 56-63 (1999).</li><li>Fran&#231;a, A. S. C., van Hulten, J. A., Cohen, M. X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-cost+and+versatile+electrodes+for+extracellular+chronic+recordings+in+rodents.">Low-cost and versatile electrodes for extracellular chronic recordings in rodents.</a> Heliyon. 6 (9), e04867 (2020).</li></ol>

TS and PvH are employees of 3Dneuro, Nijmegen, The Netherlands. 3Dneuro co-developed and produces the TD Drive.

Presented in this article is an adaptable implant for bilateral, symmetric multi-area wire electrode recordings for freely-moving rats.
The ability to easily adjust the implant by changing predefined parameters was one of the motivations for the creation of the TD Drive. While aiming to maximize the flexibility for changing parameters, inherent constraints in the relations between them necessarily impose limits to this adaptability. No limits are set by default for the anteroposterior paramete...

The multi-area nature of brain interactions during wake and sleep makes it difficult to exhaustively study the ongoing physiological processes. While approaches such as functional MRI (fMRI) and functional ultrasound (fUS) allow sampling of brain activity from whole brains1,2, they exploit neurovascular coupling to infer brain activity from hemodynamic activity, limiting their temporal resolution2. In addition, fMRI requires the placement of the research subject in an MRI scanner, prohibiting experiments with freely moving animals. Optical imaging of calcium dynamics with single or multiphoton imaging enables cell type-specific recordings of hundreds of neurons simultaneously3. However, head-mounted microscopes such as the Miniscope3, which do allow freely moving behavior, are usually limited to imaging superficial cortical areas in intact brains4. While the diameter of their field of view on the cortex can be in the order of 1 mm, the space requirements of these head-mounted microscopes can make it difficult to target several, especially adjacent, areas. Therefore, to capture multi-area brain dynamics in wake and sleep accurately, extracellular electrophysiology, recorded with electrodes implanted in the brain areas of interest, is one of the methods of choice due to its high temporal resolution and spatial precision5. In addition, it allows the characterization of sleep dynamics in animals compatible with analyses obtained from human EEG, increasing the translational value of this method6.
Classically, studies recording brain activity with extracellular electrodes have employed individual wire electrodes or electrode bundles, such as tetrodes7. State-of-the-art probes such as the Neuropixels probe8 allow targeting several areas simultaneously, given that they are aligned on an axis that allows implanting the probe along that axis without impairing the animal. However, accurate simultaneous recordings of multiple, spatially separated areas still remain challenging, with existing methods being either costly or time-intensive.
In recent years, additive manufacturing methods such as stereolithography have become broadly available. This allowed researchers to develop novel electrode implants that were adaptable to their experimental requirements9, for example, simplified repeatable targeting of multiple brain areas. Frequently, these implant designs are also shared with the academic community as open-source hardware, allowing other researchers to adapt them to their own purposes. The degree of adaptability of specific implants varies both as a result of how the implant is designed and how it is shared. Parametric modeling10 is a popular approach in computer-aided design, in which different components of the design are linked by interdependent parameters and a defined design history. Implementing a parametric approach for designing implants increases their reusability and adaptability10, as changing individual parameters automatically updates the complete designs without the need for complex re-modeling of the design. A consequential necessity is that the design itself is shared in an editable format that preserves the parametric relationships and design history. File formats that only represent geometric primitives, such as STL or STEP, make subsequent parametric modifications of published models unfeasible.
While tetrode hyperdrives11,12,13 enable recordings from dozens of tetrodes, their assembly and implantation are time-intensive, and their quality is largely dependent on the skill and experience of the individual researcher. In addition, they usually combine the guide tubes that direct the recording electrodes to their target location in one or two larger bundles, therefore limiting the number and spread of areas that can be targeted efficiently.
Other implants14,15 expose the complete skull and allow for the free placement of multiple individual microdrives that carry the recording electrodes. While the placement of independent microdrives16 during surgery time maximizes flexibility, it increases surgery time and can make it difficult to target multiple adjacent areas due to the space requirements of the individual microdrives. In addition, while the implants are open source, they are only published as STL files, making modification difficult.
An example of a drive with a more inherent parametric philosophy is the RatHat17. By providing a surgical stencil that covers the whole dorsal surface of the skull, it allows precise targeting of multiple brain targets without the use of a stereotactic frame during surgery. Multiple implant variations for cannulas, optrodes, or tetrodes are available. However, while the drive is free to use for academic purposes, it is not published open-source, creating a hurdle for researchers to evaluate and use the implant.
Presented in this article is the TD Drive (see Figure 1), a novel 3D-printable implant for extracellular electrode recordings in rats. The TD Drive aims to overcome some of the drawbacks of existing solutions: it allows to target multiple brain areas, mirrored across both hemispheres, with independent wire electrodes simultaneously. Due to its simple design, it can be assembled in a few hours at a relatively low cost by less experienced researchers. The TD Drive is published open-source, in easily modifiable file formats to allow researchers to adjust it to their specific needs. Incorporating a parametric 3D modeling approach from the beginning of the TD Drive&#39;s design process allows the parameters necessary to be changed to be abstracted: to change target locations, researchers can simply edit the parameters representing their dorsoventral and anteroposterior coordinates, without the need for re-designing the drive themselves. The files to modify and manufacture the TD Drive can be found at <a href="https://github.com/3Dneuro/TD_Drive">https://github.com/3Dneuro/TD_Drive</a>.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66457/66457fig01.jpg" /> 
Figure 1: Overview of the TD Drive. (A) Rendering of a TD Drive with a protective cap. (B) Rendering with inner parts shown. The TD Drive features (a)&#160;multiple, parametrically adjustable recording locations for fixed and moveable electrode wires, an EIB with (b) a high-density Omnetics connector compatible with common tethered and wireless data acquisition systems, and (c) an intuitive channel mapping optimized for recordings with Intan/Open Ephys systems (see Supplementary Figure 1) and (d) a cap to protect the implant during tethered recordings and when no headstage is connected. (C) A guide stencil on the bottom of the TD Drive facilitates the placement of guide cannulas and serves as a redundant verification of implant locations during surgery. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/66457/66457fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
The implant design was piloted in n = 4, validated in n = 8, and confirmed in n= 8 Lister Hooded rats that performed different tasks. The first 4 animals were used to develop the drive and adjust parameters. Then, a full pilot was run with 8 animals (shown in results). A second cohort of 8 animals was run and included in the implant survival analysis. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze (HexMaze 9 m x 5 m) using two different commercial recording systems and headstages. The two cohorts of 8 were recorded with two different acquisition systems - tethered for longer sleep recordings and wireless for large maze exploration recordings. We can conclude that this simple wire drive allows for long-running experiments with larger cohorts by less experienced researchers to enable sleep stage analysis as well as oscillation analysis in multiple brain areas. This is in contrast to most electrophysiology implants to date, which, due to difficulty and time intensity, allow for smaller animal cohorts and usually need very experienced experimenters. However, with this drive, no individual neuron activity can be recorded; thus, the use is limited to investigations of local field potential (LFP) and summation activity.

<table><tbody><tr><td>0.5 mm drill bit&amp;nbsp;</td><td>McMaster</td><td>2951A38</td><td></td></tr><tr><td>1.27 mm pitch interconnected SIP/DIP socket (Mill-Max)</td><td>Mouser Electronic</td><td>575-003101</td><td>For essembling and connection of EEG &amp;amp; GND screws</td></tr><tr><td>5 minute epoxy&amp;nbsp;</td><td>Bison</td><td>Commercially available</td><td>regular off-the-shelf epoxy</td></tr><tr><td>cyanoacrylate glue</td><td>Loctite</td><td></td><td>Super Glue-3&amp;nbsp;</td></tr><tr><td>EEG wire</td><td>Science Products GmbH</td><td>7SS-2T</td><td></td></tr><tr><td>Electrode wire</td><td>Science Products GmbH</td><td>NC7620F</td><td></td></tr><tr><td>Ethanol</td><td>LC</td><td></td><td>For standard pre-operative sterilization procedure of drive</td></tr><tr><td>Fine forceps (5)</td><td>FST</td><td>91150-20</td><td>For wire bundle preperation and handling</td></tr><tr><td>Form 3B</td><td>Formlabs</td><td></td><td>3D printer used to 3D print the self-printed parts of the TD drive</td></tr><tr><td>Gold pins (small)</td><td>Neuralynx, Inc.</td><td>9885</td><td>Attachment of electorde wires to EIB board</td></tr><tr><td>Ground wire</td><td>Science Products GmbH</td><td>SS-3T/A</td><td></td></tr><tr><td>High-density connector&amp;nbsp;</td><td>LabMaker GmbH/Omnetics</td><td>A79026-001</td><td></td></tr><tr><td>Lister Hodded rats</td><td>Charles River Laboratories</td><td>Crl:LIS</td><td>we used male rats, 9-12 weeks of age at arrival</td></tr><tr><td>M1 brass insert</td><td>AliExpress</td><td>Commercially available</td><td>https://aliexpress.com/item/33047616164.html</td></tr><tr><td>M1 tap</td><td>McMaster</td><td>2504A33</td><td></td></tr><tr><td>M1x16 screw</td><td>Bossard</td><td>1096613</td><td></td></tr><tr><td>M1x3 stainless steel screws&amp;nbsp;</td><td>Screws and More</td><td>84213_14985</td><td></td></tr><tr><td>M2.5x5 polyimide screws</td><td>Screws and more</td><td>7985PA25S_50</td><td></td></tr><tr><td>mineral oil</td><td>McMaster</td><td>1244K14</td><td></td></tr><tr><td>Nail polish</td><td>Etos</td><td>Commercially available</td><td>For color coding EEG and GND wires</td></tr><tr><td>painter&#039;s tape</td><td>Gamma</td><td>Commercially available</td><td>For wire bundle preperation</td></tr><tr><td>Pin vise</td><td>McMaster</td><td>8455A16</td><td></td></tr><tr><td>plotting paper</td><td>Canson</td><td>Commercially available</td><td>For wire bundle preperation</td></tr><tr><td>polyimide tubes</td><td>Amazon / Small Parts</td><td>TWPT-0159-30-50</td><td>AWG, 0.0159&quot; ID, 0.0219&quot; OD, 0.0030&quot; Wall, 30&quot; Length</td></tr><tr><td>RHD 32-channel headstage with accelerometer</td><td>Intan Technologies, LLC</td><td>C3324</td><td>For tethered recordings in the sleepbox</td></tr><tr><td>RHD 3-ft (0.9 m) standard SPI cables</td><td>Intan Technologies, LLC</td><td>C3203</td><td>From commutator to headstage</td></tr><tr><td>RHD 6-ft (1.8 m) standard SPI cables</td><td>Intan Technologies, LLC</td><td>C3206</td><td>From OpenEphys box to commutator</td></tr><tr><td>Slip Ring with Flange</td><td>Adafruit</td><td>1196</td><td>Commutator: 22 mm diameter, 12 wires</td></tr><tr><td>Solder flux&amp;nbsp;</td><td>Griffon S-39 50 ml</td><td>Commercially available</td><td>For soldering EEG &amp;amp; GND screws</td></tr><tr><td>soldering paste</td><td>Amazon</td><td>B08CBZ5HC5</td><td></td></tr><tr><td>stainless steel M2 nut&amp;nbsp;</td><td>McMaster</td><td>93935A305</td><td></td></tr><tr><td>Tethered recording setup&amp;nbsp;</td><td>OpenEphys</td><td>Acquasition Board</td><td></td></tr><tr><td>Wireless recording logger</td><td>SpikeGadgets</td><td>miniLogger 32</td><td>For wireless recordings in the task</td></tr><tr><td>Wireless recording setup</td><td>SpikeGadgets</td><td>Main Control Unit (MCU) incl. breakout board and RF transceiver</td><td>For wireless recordings in the task</td></tr></tbody></table>

the td drive: a parametric, open-source implant for multi&#45;area electrophysiological recordings in behaving and sleeping rats

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as the formation and consolidation of memories, are two examples that rely heavily on functional connectivity across the brain. In addition, investigating hemispheric similarities and/or differences goes hand in hand with these multi-area interactions. Electrophysiological studies trying to further elucidate these complex processes thus depend on recording brain activity at multiple locations simultaneously and often in a bilateral fashion. Presented here is a 3D-printable implant for rats, named TD Drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. The open-source design was created employing parametric design principles, allowing prospective users to easily adapt the drive design to their needs by simply adjusting high-level parameters, such as anterior-posterior and mediolateral coordinates of the recording electrode locations. The implant design was validated in n = 20 Lister Hooded rats that performed different tasks. The implant was compatible with tethered sleep recordings and open field recordings (Object Exploration) as well as wireless recording in a large maze using two different commercial recording systems and headstages. Thus, presented here is the adaptable design and assembly of a new electrophysiological implant, facilitating fast preparation and implantation.

Using the instructions provided in the protocol, the TD Drive could be built easily by multiple experimenters. After drive development (n = 4), a full pilot was run with eight animals. An additional batch of eight animals was implanted, and experimental data collection was performed. As data analysis has not been completed on these animals, they have been included in the survival analysis, but not in other analyses (e.g., targeting or histology). Implant surgery was performed 2 weeks after arrival (see <strong class="xfi...

Read this Scientific Article Protocol about The TD Drive: A Parametric, Open-Source Implant for Multi-Area Electrophysiological Recordings in Behaving and Sleeping Rats at JoVE.com

Author Spotlight: Deciphering Memory and Learning Through Neural Implants for Multi&#45;Region Brain Studies

Here, we present a unique, 3D-printable implant for rats, named TD Drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously.

The TD Drive: A Parametric, Open-Source Implant for Multi&#45;Area Electrophysiological Recordings in Behaving and Sleeping Rats

Intricate interactions between multiple brain areas underlie most functions attributed to the brain. The process of learning, as well as the formation and ...

the-td-drive-parametric-open-source-implant-for-multi-area

Research

JoVE Journal

Neuroscience

462 Views.  Radboud University. Here, we present a unique, 3D-printable implant for rats, named TD Drive, capable of symmetric, bilateral wire electrode recordings, currently in up to ten distributed brain areas simultaneously. 

Video: Author Spotlight: Deciphering Memory and Learning Through Neural Implants for Multi-Region Brain Studies

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery. Here we provide useful information for surgeons who are learning the process of implanting electrode systems. We demonstrate the implantation procedure of both a penetrating and a surface electrode. The surgical process is described from start to finish, including detailed descriptions of each step throughout the procedure. It should also be noted that this video guide is focused towards procedures conducted in rodent models and other small animal models. Modifications of the described procedures are feasible for other animal models.

We provide useful information for surgeons who are learning the process of implanting chronic neural recording electrodes. Techniques for both penetrating and surface electrode systems are described in a rodent animal model.

The success of long-term electrophysiological recordings often depends on the quality of the implantation surgery.  Here we provide useful information for ...

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described. The system operates through a single portable head stage that both transmits recorded activity and can be targeted in real-time for brain stimulation using a telemetry-based multichannel software. The head stage is equipped with a preamplifier and a rechargeable battery, allowing stable long-term recordings or stimulation for up to 1 h. Importantly, the head stage is compact, weighs 12 g (including battery) and thus has minimal impact on the animal&#180;s behavioral repertoire, making the method applicable to a broad set of behavioral tasks. Moreover, the method has the major advantage that the effect of brain stimulation on neural activity and behavior can be measured simultaneously, providing a tool to assess the causal relationships between specific brain activation patterns and behavior. This feature makes the method particularly valuable for the field of deep brain stimulation, allowing precise assessment, monitoring, and adjustment of stimulation parameters during long-term behavioral experiments. The applicability of the system has been validated using the inferior colliculus as a model structure.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

A wireless, bidirectional system for multi-channel neural recordings and stimulation in freely behaving rats is introduced. The system is light and compact, thus having minimal impact on the animal&#180;s behavioral repertoire. Moreover, this bidirectional system provides a sophisticated tool to assess causal relationships between brain activation patterns and behavior.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer ...

Behavior

High-density Electroencephalographic Acquisition in a Rodent Model Using Low-cost and Open-source Resources

Advanced electroencephalographic analysis techniques requiring high spatial resolution, including electrical source imaging and measures of network connectivity, are applicable to an expanding variety of questions in neuroscience. Performing these kinds of analyses in a rodent model requires higher electrode density than traditional screw electrodes can accomplish. While higher-density electroencephalographic montages for rodents exist, they are of limited availability to most researchers, are not robust enough for repeated experiments over an extended period of time, or are limited to use in anesthetized rodents.1-3 A proposed low-cost method for constructing a durable, high-count, transcranial electrode array, consisting of bilaterally implantable headpieces is investigated as a means to perform advanced electroencephalogram analyses in mice or rats.

Procedures for headpiece fabrication and surgical implantation necessary to produce high signal to noise, low-impedance electroencephalographic and electromyographic signals are presented. While the methodology is useful in both rats and mice, this manuscript focuses on the more challenging implementation for the smaller mouse skull. Freely moving mice are only tethered to cables via a common adapter during recording. One version of this electrode system that includes 26 electroencephalographic channels and 4 electromyographic channels is described below.

Instructions for the low-cost construction and surgical implantation of a chronic transcranial high-density electroencephalographic montage into mice are provided. Signal recording, extraction, and processing techniques are also described.

Advanced electroencephalographic analysis techniques requiring high spatial resolution, including electrical source imaging and measures of network ...

Simultaneous Recordings of Cortical Local Field Potentials, Electrocardiogram, Electromyogram, and Breathing Rhythm from a Freely Moving Rat

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls body functions and internal organ rhythms when animals are exposed to emotional challenges and changes in their living environments. In general experiments, signals from different organs, such as the brain and the heart, are recorded by independent recording systems that require multiple recording devices and different procedures for processing the data files. This study describes a new method that can simultaneously monitor electrical biosignals, including tens of local field potentials in multiple brain regions, electrocardiograms that represent the cardiac rhythm, electromyograms that represent awake/sleep-related muscle contraction, and breathing signals, in a freely moving rat. The recording configuration of this method is based on a conventional micro-drive array for cortical local field potential recordings in which tens of electrodes are accommodated, and the signals obtained from these electrodes are integrated into a single electrical board mounted on the animal's head. Here, this recording system was improved so that signals from the peripheral organs are also transferred to an electrical interface board. In a single surgery, electrodes are first separately implanted into the appropriate body parts and the target brain areas. The open ends of all of these electrodes are then soldered to individual channels of the electrical board above the animal's head so that all of the signals can be integrated into the single electrical board. Connecting this board to a recording device allows for the collection of all of the signals into a single device, which reduces experimental costs and simplifies data processing, because all data can be handled in the same data file. This technique will aid the understanding of the neurophysiological correlates of the associations between central and peripheral organs.

This study introduces a method for the simultaneous recording of local field potentials in the brain, electrocardiograms, electromyograms, and breathing signals of a freely moving rat. This technique, which reduces experimental costs and simplifies data analysis, will contribute to the understanding of the interactions between the brain and peripheral organs.

Monitoring the physiological dynamics of the brain and peripheral tissues is necessary for addressing a number of questions about how the brain controls ...

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of scientific and clinical development. The use of flexible polymer electrode arrays can support long-lasting recording, but the same mechanical properties that allow for longevity of recording make multiple insertions and integration into a chronic implant a challenge. Here is a methodology by which multiple polymer electrode arrays can be targeted to a relatively spatially unconstrained set of brain areas.
The method utilizes thin-film polymer devices, selected for their biocompatibility and capability to achieve long-term and stable&#160;electrophysiologic recording interfaces. The resultant implant allows accurate and flexible targeting of anatomically distant regions, physical stability for months, and robustness to electrical noise. The methodology supports up to sixteen serially inserted devices across eight different anatomic targets. As previously demonstrated, the methodology is capable of recording from 1024 channels. Of these, the 512 channels in this demonstration used for single neuron recording yielded 375 single units distributed across six recording sites. Importantly, this method also can record single units for at least 160 days.
This implantation strategy, including temporarily bracing each device with a retractable silicon insertion shuttle, involves tethering of devices at their target depths to a skull-adhered plastic base piece that is custom-designed for each set of recording targets, and stabilization/protection of the devices within a silicone-filled, custom-designed plastic case. Also covered is the preparation of devices for implantation, and design principles that should guide adaptation to different combinations of brain areas or array designs.

Described below is a method for implantation of multiple polymer electrode arrays across anatomically distant brain regions for chronic electrophysiological recording in freely moving rats. Preparation and surgical implantation are described in detail, with emphasis on design principles to guide adaptation of these methods for use in other species.

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of ...

Flexible Multi-Region Neural Recording Device for Epilepsy Research

An Integrated Method for Crafting Flexible and Convenient Electrophysiological Optrodes for Multi-Region In Vivo Recording

Epilepsy is a neurological disorder characterized by synchronized abnormal discharges involving multiple brain regions. Focal lesions facilitate the propagation of epileptic signals through associated neural circuits. Therefore, in vivo recording of local field potential (LFP) from the critical brain regions is&#160;essential for deciphering the circuits involved in seizure propagation. However, current methods for electrode fabrication and implantation lack flexibility. Here, we present a handy device designed for electrophysiological recordings (LFPs and electroencephalography [EEG]) across multiple regions. Additionally, we seamlessly integrated optogenetic manipulation and calcium signaling recording with LFP recording. Robust after-discharges were observed in several separate regions during epileptic seizures, accompanied by increasing&#160;calcium signaling. The approach used in this study offers a convenient and flexible strategy for synchronous neural recordings across diverse regions of the brain. It holds the potential for advancing research on neurological disorders by providing insights into the neural profiles of multiple regions involved in these disorders.

Author Spotlight: Unraveling Neural Communication and Circuit Interactions in Health and Disease

We have developed a simplified and cost-effective approach for electrode fabrication and conducted recordings of signals across multiple regions in freely moving mice. Utilizing optogenetics, alongside multi-region electrophysiology and calcium signal recording, enabled the revelation of neuronal activities across regions in the seizure kindling model.

Epilepsy is a neurological disorder characterized by synchronized abnormal discharges involving multiple brain regions. Focal lesions facilitate the ...

In Vivo Electrophysiological Recordings of Brain Activities from Multiple Sites in Rats

Source: Haumesser, J. K., et al. <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/55940">Acute In Vivo Electrophysiological Recordings of Local Field Potentials and Multi-unit Activity from the Hyperdirect Pathway in Anesthetized Rats.</a> J. Vis. Exp.(2017).
This video demonstrates the detailed procedure for preparing an anesthetized rat for electrophysiological recordings of brain activity from multiple sites. The scalp is dissected to access the skull, and holes are drilled at precise locations to install and secure electrodes. Tungsten microwire electrodes are then inserted into the targeted location to record the data.

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
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JoVE Encyclopedia of Experiments

Neurophysiology

Electrophysiology Techniques

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Source: Melo-Thomas, L., et al., <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/56299">A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats.</a> J. Vis. Exp. (2017)
The video demonstrates a procedure for implanting a wireless bidirectional multichannel electrode unit into a rat brain to record and stimulate multichannel neural networks.

Subdural Implantation of a Soft Electrocorticography Array for Cortical Electrophysiology Recording in Minipigs

Source: Fallegger, F. et al., <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/64997">Subdural Soft Electrocorticography (ECoG) Array Implantation and Long-Term Cortical Recording in Minipigs.</a>&#160;J. Vis. Exp. (2023).
This video demonstrates the implantation of a soft electrocorticography array and the long-term cortical recordings in a minipig. It outlines the steps involved in surgically implanting the array over the minipig&#39;s auditory cortex and recording both baseline and sound stimulus-evoked neuronal action potentials.

Implanting an On-Head Electrode System in a Rat Model for Real-Time Seizure Detection

Source: Koz&#225;k, G., et al. <a href="https://app-jove-com.remotexs.ntu.edu.sg/v/56669">Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats.</a> J. Vis. Exp. (2018).
This video demonstrates the method of implanting an on-head electrode system in an anesthetized rat for real-time seizure detection. The procedure includes placing stimulation and recording electrodes, securing them with dental cement, and connecting them to a head-mounted amplifier.

The TD Drive: A Parametric, Open-Source Implant for Multi-Area Electrophysiological Recordings in Behaving and Sleeping Rats

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Chapters in this video

Surgical Implantation of Chronic Neural Electrodes for Recording Single Unit Activity and Electrocorticographic Signals

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats

High-density Electroencephalographic Acquisition in a Rodent Model Using Low-cost and Open-source Resources

Simultaneous Recordings of Cortical Local Field Potentials, Electrocardiogram, Electromyogram, and Breathing Rhythm from a Freely Moving Rat

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays

An Integrated Method for Crafting Flexible and Convenient Electrophysiological Optrodes for Multi-Region In Vivo Recording

In Vivo Electrophysiological Recordings of Brain Activities from Multiple Sites in Rats

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Subdural Implantation of a Soft Electrocorticography Array for Cortical Electrophysiology Recording in Minipigs

Implanting an On-Head Electrode System in a Rat Model for Real-Time Seizure Detection