The authors are grateful to Dr. Rob Franklin (Blackrock Microsystems), Prof. Margitta Seeck (Division of Neurology, Geneva University Hospitals, Geneva, Switzerland), Dr. Andrea Bartoli and Prof. Karl Schaller (Division of Neurosurgery, Geneva University Hospitals, Geneva, Switzerland), and Mr. Florent Burdin and Prof. John P. Donoghue (Wyss Center for Bio and Neuroengineering, Geneva, Switzerland) for their support in preparing the present work.

The human cadaver used in this work was provided under the framework of body donations for medical education. Informed consent for body donation was obtained in writing during the lifetime of the donor. In accordance with the federal and cantonal laws, no review by an ethics committee was necessary.
Note: This protocol assumes that the persons performing the practice surgery are neurosurgeons with training and expertise in standard neurosurgical procedures, including patient positioning and head fixation, craniotomy and durotomy, and suturing. In addition to the tools and equipment specific to the microelectrode array, standard neurosurgical tools and equipment are used.
1. Selection of the cadaver and setup of the operating room
<ol>
	<li>Select a specimen with no history of disease or injury to the head, skull and brain.
	<ol>
		<li>Optionally, perform a computed tomography (CT) scan of the cadaver&#39;s head to ensure that there is no significant intracranial lesion (Figure 1A), e.g. chronic subdural hematoma or an intra-axial expansive lesion. Using the CT scan, identify a target cortical area for the implantation of the microelectrode array (such as the &#34;hand knob&#34; area of the precentral gyrus, corresponding to the representation of the hand in the primary motor cortex27, in the case of training for the implantation of a BCI).</li>
	</ol>
	</li>
	<li>Position cadaver in lateral decubitus on an operating table. Use an operating table rather than a dissection table in order to add to the realism of the OR-like environment and facilitates the fixation of the skull clamp and pneumatic impactor. Position the cadaver in lateral decubitus in order to allow the fronto-temporal approach in a formaldehyde-fixed cadaver, in whom neck rotation is limited.</li>
	<li>Fix the head in the skull clamp (Figure 1B). Cover with surgical drapes (Figure 1C). 
	Note: In our case, the posterior pins of skull clamp are unusually positioned in the sagittal plane of the head (see Figure 1B), because we used a skull clamp that had been modified for surgical training purposes to hold a cadaveric head separated from the rest of the body.
	<ol>
		<li>When using a standard skull clamp on an operating table, place the posterior pins securing the head perpendicular to the sagittal plane.</li>
	</ol>
	</li>
</ol>
2. Exposure of the neocortical surface
<ol>
	<li>Incise the scalp using a scalpel, following a question-mark incision to expose the temporal and frontal bones. Dissect the temporalis muscle along the posterior edge of the incision. Recline the scalp and temporalis muscle by blunt dissection (Figure 1D).</li>
	<li>Perform a large square fronto-temporal craniotomy, e.g. 5 x 5 cm (Figure 2A). For that purpose, drill four burr holes at the corners of the intended craniotomy. Then, use the craniotome to connect the burr holes. Remove the bone flap using a spatula, exposing the dura mater. Store the bone flap in saline solution.</li>
	<li>Open the dura mater on three sides of the craniotomy using dura scissors (Figure 2B). Recline it and expose the arachnoid membrane and the surface of the cerebral neocortex (Figure 2C).</li>
</ol>
3. Fixation of the electrode pedestal
<ol>
	<li>Select a cortical gyrus where the microelectrode array will be implanted. Select a gyral surface that is approximately flat so that the microelectrode array will lie flush with it when inserted. Ensure that there is no visible blood vessel coursing on the cortical surface where the microelectrode array will be inserted.</li>
	<li>Select a site for the fixation of the electrode pedestal on the superior edge of the craniotomy, close to the skin incision, and allowing sufficient slack for the wire bundle so that the microelectrode array can reach the target gyrus. Screw the pedestal onto the external table of the skull bone next to the craniotomy (Figure 2D). Use 6 to 8 self-tapping cortical bone screws (6 mm length, 2 mm diameter) to ensure appropriate fixation.
	<ol>
		<li>When manipulating the pedestal, always ensure that the microelectrode array does not touch anything (it may be damaged or could lacerate the neocortical surface) by holding the wire bundle close to the microelectrode array with tweezers with plastic- or rubber-coated tips (Figure 2E).</li>
	</ol>
	</li>
</ol>
4. Positioning and insertion of the microelectrode array
<ol>
	<li>Position the microelectrode array parallel with the surface of the target gyrus. Bend the wire bundle as necessary for that purpose (Figure 3A). 
	Note: The stiff wire bundle does not easily conform to the surgeon&#39;s wishes. Care and patience are required to obtain good alignment of the microelectrode array and cortical surface.
	<ol>
		<li>Optionally, use &#34;dog-bone&#34; titanium straps to secure the wire bundle to the skull and control its course toward the target gyrus. Do not screw the strap too tightly to avoid damaging the wire bundle.</li>
	</ol>
	</li>
	<li>Bring the pneumatic impactor into approximate alignment with the back of the microelectrode array (Figure 3B). Control the connections of the pneumatic impactor to its control box, and then turn on the control box. 
	Note: Make sure that the pneumatic impactor is at least 5 mm away from the array before turning the control box on, as the pneumatic impactor might be triggered when first turned on.</li>
	<li>Use the millimetric screws of the pneumatic impactor holder to refine the impactor&#39;s alignment with the back of the microelectrode array (Figure 3B, inset). Using the impactor, apply an excursion distance- and pressure-controlled tap to the back of the microelectrode array and insert it into the cortical surface, pushing it through the arachnoid membrane. 
	Note: Check that the microelectrode array is flush with the cortical surface.</li>
</ol>
5. Positioning of the subdural ECOG grid
Note: This step is optional.
<ol>
	<li>Position a subdural ECOG grid over the exposed cortical surface (Figure 3D). If necessary, remove electrodes by cutting through the grid so that the overall shape of the ECOG grid fits the craniotomy.</li>
	<li>Orient the ECOG grid so that its wires will exit the dura mater and skull superiorly or posteriorly.</li>
	<li>Irrigate the ECOG grid with saline before placing it into contact with the cortical surface.</li>
	<li>Secure the ECOG grid by suturing it to the dura mater at the edges of the durotomy.</li>
</ol>
6. Repositioning and closure of the dura mater, bone flap, and skin flap
<ol>
	<li>Reflect the dura mater back over the exposed cortical surface and suture it to the edges of the durotomy.</li>
	<li>Screw &#34;dog-bone&#34; titanium straps onto the edges of the bone flap using self-tapping cortical bone screws. Reposition the bone flap within the craniotomy. Secure the bone flap to neighboring skull bones with the &#34;dog-bone&#34; titanium straps and self-tapping cortical bone screws. Take care not to crush the wire bundle of the microelectrode array (and those of the optional ECOG grid) between bone edges.</li>
	<li>Reflect and suture the skin flap. Close the skin incision around the neck of the electrode pedestal (Figure 3E).
	<ol>
		<li>Alternatively, allow the pedestal to egress the scalp through a separate stab incision made into the scalp flap.</li>
	</ol>
	</li>
</ol>

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<li>Del Castillo-Calcáneo, J., Donoghue, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+Novel+Method+for+3-Dimensional+Printing+a+Brain+That+Feels+and+Looks+Like+One%3A+The+Next+Step+in+the+Search+of+the+Perfect+Neurosurgical+Simulator%5BTitle%5D)+AND+%22World+Neurosurg%22%5BJournal%5D)">A Novel Method for 3-Dimensional Printing a Brain That Feels and Looks Like One: The Next Step in the Search of the Perfect Neurosurgical Simulator.</a> World Neurosurg. 91, 620-622 (2016).</li>
<li>Martin, S., Millán, J. D. R., Knight, R. T., Pasley, B. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((The+use+of+intracranial+recordings+to+decode+human+language%3A+Challenges+and+opportunities%5BTitle%5D)+AND+%22Brain+Lang%22%5BJournal%5D)">The use of intracranial recordings to decode human language: Challenges and opportunities.</a> Brain Lang. , (2016).</li>
</ol>

The authors have nothing to disclose.

The formaldehyde-fixed human cadaver model and the surgical protocol described here replicate the surgical procedure of implanting microelectrode arrays into the human cerebral neocortex. Each step of the procedure, including the positioning of the microelectrode array and its insertion with the pneumatic inserter, proceed in almost the same fashion as in a real-life patient, with the exception that cerebral pulsation and circulation are absent. The critical steps in the protocol are the alignment of the microelectrode a...

Recent years have seen the development of technological solutions to the challenge of recording the activity of multiple individual neurons in the living brain1,2,3. Silicon-based microelectrode arrays perform similarly to conventional wire microelectrodes in terms of signal properties, and they can record from dozens to hundreds of neurons in a small patch of cerebral tissue4,5,6,7. Microelectrode arrays have allowed scientists to establish the correspondence between neural activity in the primary motor cortex of monkeys and arm movements8, which in turn has provided a boost to the development of brain-computer interfaces (BCIs)9.
Microelectrode arrays have been used in humans in two situations: as chronic implants to control BCIs and as semi-chronic implants to study the activity of individual neurons in patients suffering from epilepsy. Chronic implants, targeting the functional representation of the hand in primary motor cortex, have allowed patients suffering from tetraplegia to control the motion of a robotic arm or of computer cursors10,11,12,13. Semi-chronic implants, inserted together with subdural electrocorticography (ECOG) electrodes in patients with drug-resistant epilepsy who are candidates for epilepsy surgery14, allow single-unit recordings before, during and after seizures, and have begun to shed light on the activity of single neurons during and in between epileptic seizures15,16,17,18,19. Microelectrode arrays have the potential to significantly improve our understanding of how the brain functions by establishing a link between the activity of neurons, on the one hand, and the perceptions, movements and thoughts of human beings, both in health and in disease, on the other20,21.
Silicon-based microelectrode arrays are now available commercially and their use in humans has been approved by regulatory authorities in the USA in the semi-chronic epilepsy indication. However, these devices are invasive and must be inserted into the brain. The negative consequences of improper insertion technique, beyond the failure of the device to record neuronal activity, include cerebral hemorrhage and infection, with the potential for long-lasting or permanent neurological dysfunction. Although the complication rate of microelectrode array implantation is currently unknown, the rate of potentially serious complications during the implantation of intracranial electroencephalography (EEG) macroelectrodes is 1-5%22,23. Therefore, the proper implantation of microelectrode arrays requires both extensive neurosurgical skills and procedure-specific training.
The approaches available for surgeons to hone their skills with microelectrode arrays in a safe environment include non-human mammals and human cadavers. The ideal training model would faithfully reproduce the size and thickness of the human skull; the toughness and vascular ramification of the dura; the gyrification pattern, consistency and pulsation of the human brain; the presence of circulating blood and cerebrospinal fluid; and the overall positioning of the subject in an operating room (OR)-like environment. Thus, animal models need to be of a sufficient size to provide a meaningful experience to the surgeons. Large non-human primates come closest, but their use for surgical training is unsustainable both from an ethical perspective and because they are expensive. Rodents do not enter consideration because of their small size; using even cats or rabbits implies diverging significantly from an OR-like environment.
Human cadavers represent an attractive alternative. Their advantages include the life-like size and shape of the head and brain and the possibility of setting up surgical training in an OR-like environment. The most obvious departures from a realistic situation are the absence of cerebral pulsations and bleeding and the modifications in the aspect and consistence of body tissues that are specific to the technique employed for cadaver preservation24. Fresh-frozen cadavers preserve the consistency and flexibility of many organs and tissues to some extent, but they have several drawbacks: they start degrading as soon as thawing begins, so that the brain becomes too degraded for the insertion of a microelectrode array to be performed realistically, and they are a relatively rare and expensive resource. Formaldehyde-fixed cadavers, on the other hand, are more affordable and available and much more durable, at the expense of hardened tissue consistency.
Here, we establish a procedure using a formaldehyde-fixed human cadaver model to provide neurosurgical training for the implantation of a neocortical microelectrode array. Our approach allows realistic, OR-like positioning and instrumentation; performing craniotomy and durotomy and exposing the neocortical surface; attaching the electrode pedestal to the skull bone neighboring the craniotomy; and inserting the microelectrode array into the neocortex with a pneumatic impactor25. Critically, it enables surgeons to practice the precise alignment of the microelectrode array (which is connected to the electrode pedestal by a bundle of individually insulated gold wires) parallel to the neocortical surface26. Our protocol faithfully replicates the indication of microelectrode array implantation together with ECOG implantation in patients who are candidates for epilepsy surgery. The particulars of the implantation surgery are influenced significantly by the exact type of microelectrode array; here, we describe the procedure for an array that recently received regulatory approval for use in humans in the USA. The so-called Utah array comprises a 4x4 mm, 100 microelectrode grid; a transcutaneous pedestal that is attached to the external table of the skull; and a wire bundle connecting the two.

<table><tbody><tr><td>Mayfield skull clamp</td><td>Integra LifeSciences, Cincinnati, OH</td><td>A1059</td><td></td></tr><tr><td>Midas Rex MR7 system for craniotomy</td><td>Medtronic, Minneapolis, MN</td><td>EC300</td><td></td></tr><tr><td>Dura scissors</td><td>Sklar Surgical Instruments, West Chester, PA</td><td>22-2742</td><td></td></tr><tr><td>Self-tapping bone screws</td><td>OrthoMed Inc., Tigard, OR</td><td>OM SYN211806</td><td></td></tr><tr><td>Microelectrode array and pedestal</td><td>Blackrock Microsystems, Salt Lake City, UT</td><td>LB-0612</td><td>Mock-up arrays are available from the manufacturer upon request</td></tr><tr><td>Pneumatic impacter</td><td>Blackrock Microsystems, Salt Lake City, UT</td><td>LB-0088</td><td></td></tr><tr><td>64-channel electrocorticography grid</td><td>Ad-Tech Medical Instrument Corporation, Racine, WI</td><td>FG64C-SP10X-0C6</td><td>Optional</td></tr></tbody></table>

surgical training for the implantation of neocortical microelectrode arrays using a formaldehyde-fixed human cadaver model

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. Recent technological progress has enabled the fabrication of microelectrode arrays that allow recording the activity of multiple individual neurons in the neocortex of the human brain. These arrays have the potential to bring unique insight onto the neuronal correlates of cerebral function in health and disease. Furthermore, the identification and decoding of volitional neuronal activity opens the possibility to establish brain-computer interfaces, and thus might help restore lost neurological functions. The implantation of neocortical microelectrode arrays is an invasive procedure requiring a supra-centimetric craniotomy and the exposure of the cortical surface; thus, the procedure must be performed by an adequately trained neurosurgeon. In order to provide an opportunity for surgical training, we designed a procedure based on a human cadaver model. The use of a formaldehyde-fixed human cadaver bypasses the practical, ethical and financial difficulties of surgical practice on animals (especially non-human primates) while preserving the macroscopic structure of the head, skull, meninges and cerebral surface and allowing realistic, operating room-like positioning and instrumentation. Furthermore, the use of a human cadaver is closer to clinical daily practice than any non-human model. The major drawbacks of the cadaveric simulation are the absence of cerebral pulsation and of blood and cerebrospinal fluid circulation. We suggest that a formaldehyde-fixed human cadaver model is an adequate, practical and cost-effective approach to ensure proper surgical training before implanting microelectrode arrays in the living human neocortex.

Our protocol uses a formaldehyde-fixated human cadaver model to allow surgeons to practice the surgical procedure of implanting a microelectrode array into the cerebral neocortex in a realistic, OR-like environment. The option of performing post-mortem neuroimaging, such as head CT, will confirm the absence of any significant intracranial lesion (Figure 1A) and can help with the selection of the implantation site. Working with an entire specimen and setting up for surgery on an operating tab...

Watch this Scientific Journal Video about Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model at JoVE.com

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

We designed a procedure in which a formaldehyde-fixed human cadaver is used to assist neurosurgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain.

This protocol describes a procedure to assist surgeons in training for the implantation of microelectrode arrays into the neocortex of the human brain. ...

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Research

JoVE Journal

Medicine

11.3K Views.  Wyss Center for Bio and Neuroengineering, Geneva. We ontwierpen een procedure waarin een formaldehyde-vaste menselijke cadaver wordt gebruikt bij neurochirurgen in opleiding voor de inplanting van micro-elektrode arrays in de neocortex van het menselijk brein.

Video: Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

Combined Shuttle-Box Training with Electrophysiological Cortex Recording and Stimulation as a Tool to Study Perception and Learning

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the necessary equipment is now available by several commercial companies. This protocol provides a detailed description of a two-way shuttle-box avoidance learning paradigm in rodents (here Mongolian gerbils; Meriones unguiculatus) in combination with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical electrophysiological in vivo recordings. The detailed protocol is applicable to study multiple aspects of learning behavior and perception in different rodent species.
Site-specific ICMS of auditory cortical circuits as conditioned stimuli here is used as a tool to test the perceptual relevance of specific afferent, efferent and intracortical connections. Distinct activation patterns can be evoked by using different stimulation electrode arrays for local, layer-dependent ICMS or distant ICMS sites. Utilizing behavioral signal detection analysis it can be determined which stimulation strategy is most effective for eliciting a behaviorally detectable and salient signal. Further, parallel multichannel-recordings using different electrode designs (surface electrodes, depth electrodes, etc.) allow for investigating neuronal observables over the time course of such learning processes. It will be discussed how changes of the behavioral design can increase the cognitive complexity (e.g. detection, discrimination, reversal learning).

Shuttle-box avoidance learning is well-established in behavioral neuroscience. This protocol describes how shuttle-box learning in rodents can be combined with site-specific electrical intracortical microstimulation (ICMS) and simultaneous chronical in vivo recordings as a tool to study multiple aspects of learning and perception.

Shuttle-box avoidance learning is a well-established method in behavioral neuroscience and experimental setups were traditionally custom-made; the ...

Behavior

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 ...

Neuroscience

Large-scale Recording of Neurons by Movable Silicon Probes in Behaving Rodents

A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of neurons and circuits requires methods with the spatial selectivity and temporal resolution appropriate for mechanistic analysis of neural ensembles in the behaving animal, i.e. recording of representatively large samples of isolated single neurons. Ensemble monitoring of neuronal activity has progressed remarkably in the past decade in both small and large-brained animals, including human subjects1-11. Multiple-site recording with silicon-based devices are particularly effective because of their scalability, small volume and geometric design.
Here, we describe methods for recording multiple single neurons and local field potential in behaving rodents, using commercially available micro-machined silicon probes with custom-made accessory components. There are two basic options for interfacing silicon probes to preamplifiers: printed circuit boards and flexible cables. Probe supplying companies (<a href="http://www.neuronexustech.com/" >http://www.neuronexustech.com/</a>; <a href="http://www.sbmicrosystems.com/">http://www.sbmicrosystems.com/</a>; <a href="http://www.acreo.se/">http://www.acreo.se/</a>) usually provide the bonding service and deliver probes bonded to printed circuit boards or flexible cables. Here, we describe the implantation of a 4-shank, 32-site probe attached to flexible polyimide cable, and mounted on a movable microdrive. Each step of the probe preparation, microdrive construction and surgery is illustrated so that the end user can easily replicate the process.

We describe methods for large-scale recording of multiple single units and local field potential in behaving rodents with silicon probes. Drive fabrication, probe attachment to the drive and probe implantation processes are illustrated in sufficient details for easy replication.

A major challenge in neuroscience is linking behavior to the collective activity of neural assemblies. Understanding of input-output relationships of ...

Intact Histological Characterization of Brain-implanted Microdevices and Surrounding Tissue

Research into the design and utilization of brain-implanted microdevices, such as microelectrode arrays, aims to produce clinically relevant devices that interface chronically with surrounding brain tissue. Tissue surrounding these implants is thought to react to the presence of the devices over time, which includes the formation of an insulating "glial scar" around the devices. However, histological analysis of these tissue changes is typically performed after explanting the device, in a process that can disrupt the morphology of the tissue of interest.
Here we demonstrate a protocol in which cortical-implanted devices are collected intact in surrounding rodent brain tissue. We describe how, once perfused with fixative, brains are removed and sliced in such a way as to avoid explanting devices. We outline fluorescent antibody labeling and optical clearing methods useful for producing an informative, yet thick tissue section. Finally, we demonstrate the mounting and imaging of these tissue sections in order to investigate the biological interface around brain-implanted devices.

Here we present a histological method for capturing, labeling, optically clearing, and imaging the intact brain tissue interface around chronically implanted microdevices in rodent brain tissue. Results from the techniques comprising this method are useful for understanding the impact of various penetrating brain-implants on their surrounding tissue.

Research  into the design and utilization of brain-implanted microdevices, such as  microelectrode arrays, aims to produce clinically relevant devices ...

Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent development of thin, flexible ECoG electrodes has enabled conduction of stable recordings of large-scale cortical activity. We have developed a whole-cortical ECoG array for the common marmoset. The array continuously covers almost the entire lateral surface of cortical hemisphere, from the occipital pole to the temporal and frontal poles, and it captures whole-cortical neural activity in one shot. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain. Marmosets have two advantages regarding ECoG recordings, one being the homologous organization of anatomical structures in humans and macaques, including frontal, parietal, and temporal complexes. The other advantage is that the marmoset brain is lissencephalic and contains a large number of complexes, which are more difficult to access in macaques with ECoG, that are exposed to the brain surface.These features allow direct access to most cortical areas beneath the surface of the brain. This system provides an opportunity to investigate global cortical information processing with high resolutions at a sub-millisecond order in time and millimeter order in space.

We have developed a whole-cortical electrocorticographic array for the common marmoset that continuously covers almost the entire lateral surface of cortex, from the occipital pole to the temporal and frontal poles. This protocol describes a chronic implantation procedure of the array in the epidural space of the marmoset brain.

Electrocorticography (ECoG) allows the monitoring of electrical field potentials from the cerebral cortex with high spatiotemporal resolution. Recent ...

Stereotaxic Surgery for Implantation of Microelectrode Arrays in the Common Marmoset (Callithrix jacchus)

Marmosets (Callithrix jacchus) are small non-human primates that are gaining popularity in biomedical and preclinical research, including the neurosciences. Phylogenetically, these animals are much closer to humans than rodents. They also display complex behaviors, including a wide range of vocalizations and social interactions. Here, an effective stereotaxic neurosurgical procedure for implantation of recording electrode arrays in the common marmoset is described. This protocol also details the pre- and postoperative steps of animal care that are required to successfully perform such a surgery. Finally, this protocol shows an example of local field potential and spike activity recordings in a freely behaving marmoset 1 week after the surgical procedure. Overall, this method provides an opportunity to study the brain function in awake and freely behaving marmosets. The same protocol can be readily used by researchers working with other small primates. In addition, it can be easily modified to allow other studies requiring implants, such as stimulating electrodes, microinjections, implantation of optrodes or guide cannulas, or ablation of discrete tissue regions.

Stereotaxic Surgery for Implantation of Microelectrode Arrays in the Common Marmoset Callithrix jacchus

This work presents a protocol to perform a stereotaxic, neurosurgical implantation of&#160;microelectrode arrays in the common marmoset. This method specifically enables electrophysiological recordings in freely behaving animals but can be easily adapted to any other similar neurosurgical intervention in this species (e.g., cannula for drug administration or electrodes for brain stimulation).

Marmosets (Callithrix jacchus) are small non-human primates that are gaining popularity in biomedical and preclinical research, including the ...

Preparation and Implantation of Electrodes for Electrically Kindling VGAT-Cre Mice to Generate a Model for Temporal Lobe Epilepsy

It was discovered that electrical kindling of VGAT-Cre mice led to the spontaneous motor and electrographic seizures. A recent paper focused on how unique VGAT-Cre mice were used in developing spontaneous recurring seizures (SRS) after kindling and a likely mechanism - insertion of Cre into the VGAT gene - disrupted its expression and reduced GABAergic tone. The present study extends these observations to a larger cohort of mice, focusing on key issues such as how long the SRS continues after kindling and the effect of the animal's sex and age. This report describes the protocols for the following key steps: making headsets with hippocampal depth electrodes for electrical stimulation and for reading the electroencephalogram; surgery to affix the headset securely on the mouse's skull so that it does not fall off; and key details of the electrical kindling protocol such as duration of the pulse, frequency of train, duration of train, and amount of current injected. The kindling protocol is robust in that it reliably leads to epilepsy in most VGAT-Cre mice, providing a new model to test for novel antiepileptogenic drugs.

This report describes the methods to generate a model of temporal lobe epilepsy based on the electrical kindling of transgenic VGAT-Cre mice. Kindled VGAT-Cre mice may be useful in determining what causes epilepsy and for screening novel therapies.

It was discovered that electrical kindling of VGAT-Cre mice led to the spontaneous motor and electrographic seizures. A recent paper focused on how unique ...

A Cost-Effective, Versatile Probe Implant System for Electrophysiology in Mice

The DREAM Implant: A Lightweight, Modular, and Cost-Effective Implant System for Chronic Electrophysiology in Head-Fixed and Freely Behaving Mice

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. However, current methods for chronically implanting probes present steep trade-offs between cost, ease of use, size, adaptability, and long-term stability.
This protocol introduces a novel chronic probe implant system for mice called the DREAM (Dynamic, Recoverable, Economical, Adaptable, and Modular), designed to overcome the trade-offs associated with currently available options. The system provides a lightweight, modular and cost-effective solution with standardized hardware elements that can be combined and implanted in straightforward steps and explanted safely for recovery and multiple reuse of probes, significantly reducing experimental costs.
The DREAM implant system integrates three hardware modules: (1) a microdrive that can carry all standard silicon probes, allowing experimenters to adjust recording depth across a travel distance of up to 7 mm; (2) a three-dimensional (3D)-printable, open-source design for a wearable Faraday cage covered in copper mesh for electrical shielding, impact protection, and connector placement, and (3) a miniaturized head-fixation system for improved animal welfare and ease of use. The corresponding surgery protocol was optimized for speed (total duration: 2 h), probe safety, and animal welfare.
The implants had minimal impact on animals&#39; behavioral repertoire, were easily applicable in freely moving and head-fixed contexts, and delivered clearly identifiable spike waveforms and healthy neuronal responses for weeks of post-implant data collection. Infections and other surgery complications were extremely rare.
As such, the DREAM implant system is a versatile, cost-effective solution for chronic electrophysiology in mice, enhancing animal well-being, and enabling more ethologically sound experiments. Its design simplifies experimental procedures across various research needs, increasing accessibility of chronic electrophysiology in rodents to a wide range of research labs.

Here, we introduce a lightweight, cost-effective probe implant system for chronic electrophysiology in rodents optimized for ease of use, probe recovery, experimental versatility, and compatibility with behavior.

Chronic electrophysiological recordings in rodents have significantly improved our understanding of neuronal dynamics and their behavioral relevance. ...

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Source: Melo-Thomas, L., et al., <a href="https://app.jove.com/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.

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.
1. ...

JoVE Encyclopedia of Experiments

Neurophysiology

Electrophysiology Techniques

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/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.

Surgical Training for the Implantation of Neocortical Microelectrode Arrays Using a Formaldehyde-fixed Human Cadaver Model

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