The authors would like to thank Bernardo Luiz for technical assistance with filming and editing. This work was supported by Santos Dumont Institute (ISD), Brazilian Ministry of Education (MEC) and Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior (CAPES).

Animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Santos Dumont Institute Ethics Committee (protocol 02/2015AAS).
1. Surgery preparation
<ol>
	<li>Attach each electrode array to an electrode holder compatible with the stereotaxic frame to be used.</li>
	<li>Connect one electrode holder to the stereotaxic micromanipulator and set one microwire to the interaural coordinates. Repeat this for the additional electrode arrays and holders, if necessary. 
	NOTE: The interaural coordinate of any microwire can be used to calculate the implantation coordinates for the entire array, because the relative distance between the microwires is constant. When the array has bundles with different lengths, the interaural coordinate of the longest wire is the most convenient to use for setting the interaural zero.</li>
	<li>Detach the electrode holders from the stereotaxic micromanipulator and sterilize the assemblies (electrode attached to the electrode holder)&#160;in an ultraviolet light (UV) cabinet for at least 2 h.</li>
	<li>Attach a 24 G needle to a stereotaxic probe holder, connect it to the micromanipulator and set the interaural coordinates for the tip of the needle. 
	NOTE: Prior to the surgery, the coordinates of all craniotomies must be predefined as a perimeter 200 &#181;m2 larger than the anteroposterior (AP) and mediolateral (ML) position of the array&#8217;s target implantation site. Use the 24 G needle-probe holder assembly to determine the position of the craniotomies in the skull based on the zero interaural coordinates.</li>
	<li>Detach the probe holder from the micromanipulator and sterilize the assembly in a UV cabinet for at least 2 h.</li>
	<li>Gather 6&#8722;8 titanium or stainless-steel screws. Solder a ground wire to half of them.</li>
	<li>Organize and sterilize all remaining instruments, equipment, and disposables required for the surgery.</li>
</ol>
2. Preoperative procedures
NOTE: Two adult male marmosets (Callithrix jacchus) weighing 320&#8211;370 g were used in this study. Ensure that the animal has not eaten for 6 h prior to the induction of anesthesia.
<ol>
	<li>Anesthetize the animal with an intramuscular injection of atropine (0.05 mg/kg) to reduce salivation and bronchial secretions. Check for the lack of pedal responses.</li>
	<li>After 5 min apply ketamine (10&#8722;20 mg/kg) intramuscularly.</li>
	<li>Shave the animal&#8217;s head using an electric barber clipper.</li>
	<li>Administer tramadol (2 mg/kg) intramuscularly as a general analgesic.</li>
	<li>Intubate the animal.
	<ol>
		<li>Using a mask, expose the marmoset to isoflurane in 1&#8722;2% oxygen with a flow rate of 1&#8722;5 L/min to induce deep anesthesia. When the animal is deeply anesthetized, reduce and maintain isoflurane to 1&#8722;3 L/min.</li>
		<li>Attach an elastic band to the surgical table with tape.</li>
		<li>Position the marmoset in a supine position with the head toward the technician and place the elastic band in the marmoset&#8217;s mouth behind its canines. 
		NOTE: It is best to position the head such that the dorsal surface is pointed toward the floor and its face is toward the technician.</li>
		<li>Using a cotton-tipped probe, swab dry the marmoset&#8217;s tongue, and grasp it in one hand to keep the mouth open.</li>
		<li>Spray 10% lidocaine on the tip of the endotracheal tube.</li>
		<li>Insert the uncuffed, 2.0 mm diameter endotracheal tube into the trachea until the 4.0 cm mark is at the entrance of the trachea.</li>
		<li>Attach the tube to the anesthesia assembly with the artificial ventilator&#160;set to 40 breaths/min and confirm proper expansion and contraction of the chest. 
		NOTE: At this time the isoflurane and oxygen should be delivered via the endotracheal tube, not the mask.</li>
		<li>Remove the elastic band from the marmoset&#8217;s mouth so the endotracheal tube can be taped to the jaw.</li>
	</ol>
	</li>
	<li>Position the marmoset in a prone position in line with the stereotaxic frame and fix the animal&#8217;s head into the stereotaxic frame.
	<ol>
		<li>First, insert the tip of the right ear bar into the animal&#8217;s right auditory canal.</li>
		<li>Next, insert the tip of the left ear bar into the left auditory canal.</li>
		<li>Center the animal&#8217;s head at the center of the stereotaxic frame and fix the ear bars in place.</li>
		<li>Insert the mouthpiece into the animal&#8217;s mouth and adjust its height so that it touches the animal&#8217;s palate. At the same time, position the orbital bars at the lower surface of the orbital bone.</li>
		<li>Make sure that the lower surface of the orbital bone is horizontally aligned with the center of the ear bars.</li>
	</ol>
	</li>
	<li>Connect a portable pulse oximeter to the marmoset&#8217;s hand. Ensure that the heart rate is within 154&#8722;180 beats/min (bpm) for the duration of the surgery; often a heart rate above 200 bpm implies the animal is waking up. Ensure that the oxygen saturation is above 95%. It may occasionally drop to 90% without harm. 
	NOTE: Should the heart rate drop below 154 bpm, decrease the isoflurane.</li>
	<li>Position the rectal temperature probe connected to a homeothermic heating pad into the anus, with the desired temperature set for 37 &#176;C. Tape this sensor to the tail to keep it fixed in place.</li>
	<li>Apply sterile ophthalmic lubricant to the eyes.</li>
	<li>Clean and disinfect the animal&#8217;s head with chlorhexidine and povidone iodine before covering the animal with a surgical field. 
	NOTE: Carry out all the following surgical procedures under aseptic conditions.</li>
</ol>
3. Surgery procedures
<ol>
	<li>Apply local analgesic subcutaneously (e.g., lidocaine 20 mg/mL, 0.1 mL) at the site of the intended incision. Make an incision in the midline of the scalp.</li>
	<li>Expose and prepare the surface of the skull.
	<ol>
		<li>Carefully detach the temporal muscle from the cranium. First, use a scalpel to cut the fascia at its insertion into the skull. Then, gently separate the temporal muscle from the cranium using a periosteal raspatory.</li>
		<li>Remove the periosteum from all exposed cranium using a periosteal raspatory.</li>
		<li>Control the bleeding with a sterile cotton swab, if necessary.</li>
		<li>Clean the bone surface with hydrogen peroxide.</li>
	</ol>
	</li>
	<li>Delineate the location of the craniotomy by marking its corners with shallow burr holes into the bone surface. Then, drill out the perimeter of the craniotomy using a dental drill at maximum speed (i.e., 350,000 rpm). Add a few drops of sterile saline over the skull while drilling to prevent overheating. Measure the position of the craniotomy and the coordinates of the electrode implant with respect to the interaural coordinates.</li>
	<li>Implant screws into the skull.
	<ol>
		<li>Drill 6&#8722;8 screw holes into the cranium.</li>
		<li>Implant the screws such that each ground wire fused screw is adjacent to and in the proximity of an unaltered screw (i.e., without a ground wire attached to it).</li>
		<li>Wind each ground wire around the adjacent, unaltered screw.</li>
		<li>Add a drop of silver paint between the ground wire and each screw.</li>
	</ol>
	</li>
	<li>Remove the bone at the center of the craniotomy using forceps with a curved tip (e.g., McPherson forceps). Keep the dura mater hydrated with sterile saline.</li>
	<li>Remove the dura mater. Use a sterile hypodermic needle (25 or 26 G) with the bevel bent at approximately 90&#730; to puncture and lift the surface of the dura mater away from the brain surface. Then, cut the dura mater with microscissors. Keep the exposed brain hydrated with saline. 
	NOTE: If significant dural bleeding is observed, use cautery or sterile absorbent gelatin sponges soaked in thrombine25.</li>
	<li>Implant microelectrode arrays.
	<ol>
		<li>Attach the sterilized electrode holder and electrode array to the stereotaxic micromanipulator.</li>
		<li>Position the micromanipulator such that the electrode is at the desired anteroposterior and mediolateral coordinates.</li>
		<li>Lower the electrode array until the tip of the longest bundle touches the surface of the brain.</li>
		<li>Slowly insert the array into the brain tissue until it reaches the dorsoventral coordinates.</li>
		<li>Cover the exposed cortex with small pieces of sterile, absorbent gelatin sponges.</li>
		<li>Secure the electrode to the skull by applying dental acrylic to the exposed skull, one screw, and the electrode.</li>
		<li>Detach the electrode holder and remove it from the micromanipulator.</li>
	</ol>
	</li>
	<li>Repeat the implantation procedure from step 3.7 with the additional arrays, if necessary.</li>
	<li>Wind together and weld the ground wires of the separate arrays and screws. Use silver paint to form a bridge around the weld to ensure an electrical connection has been achieved.</li>
	<li>Using dental acrylic, make a sturdy headcap around the lateral extent of the arrays, and completely encase the ground wires and any exposed skull and screws.</li>
	<li>If necessary, insert a support bar into the headcap. This can be a sturdy plastic cylinder like those from a cotton swab. Seal it into place with the dental acrylic. 
	NOTE: This can be helpful in securing the electrophysiology cable connectors in place but may be unnecessary depending on the equipment used. In the present method, a similar support rod is affixed to the head stage such that an elastic band can robustly hold the head stages in place on the connectors.</li>
	<li>Suture the skin around the headcap.</li>
</ol>
4. Postoperative recovery
<ol>
	<li>Apply antiseptic solution (e.g., chlorhexidine) around the wound.</li>
	<li>Turn off the isoflurane supply but not the oxygen and remove the animal from the stereotaxic frame.</li>
	<li>Place the animal onto the heating pad with the oxygen maintained through the endotracheal tube.</li>
	<li>Remove the endotracheal tube when the first signs of neurogenic reflexes, such as laryngospasms, are observed.</li>
	<li>Keep supplying the oxygen with a mask until the animal presents clear signs of anesthetic recovery, such as protective reflexes, postural tone, and attempts to ambulate.</li>
	<li>Place the animal inside a clean cage in a recovery room for 24&#8722;48 h before moving the animal to its home cage. House each implanted animal individually. 
	NOTE: Because marmosets tend to climb the cage walls, use a cage with smooth walls or cover the cage walls with a smooth surface to prevent the animal from falling.</li>
	<li>In the first hour following surgery, observe the animal to watch for signs of distress or uncoordinated head contact against the side of the cage.</li>
	<li>Administer antibiotics (e.g., enrofloxacin 5 mg/kg, subcutaneously, once a day for 5&#8722;7 days), analgesics (e.g., oral tramadol 1 mg/kg, every 8 h for 3&#8722;5 days) and anti-inflammatory drugs (e.g., dexamethasone&#160;0.5&#8722;1.5 mg/kg, subcutaneously, once a day for 1&#8722;3 days). 
	NOTE: After a successful surgery, animals will be fully recovered within 3&#8722;5 days.</li>
</ol>
5. Chronic electrophysiological recordings in freely behaving marmosets
<ol>
	<li>Start the electrophysiological recording sessions at least 1 week after the surgery. 
	NOTE: Habituate the animals to the researcher and experimental environments before starting all experimental procedures for at least 1 month.</li>
	<li>At the beginning of each session, lightly anesthetize the animal using isoflurane (1&#8722;5 L/min, 1% O2). 
	NOTE: Follow the relevant institution&#8217;s guidelines regarding the sedation of small primates. If recording sessions are very frequent, habituate the animals to be handled so that cables can be connected without anesthesia.</li>
	<li>Connect the electrode arrays to a commercial neural recording system.</li>
	<li>Place the animal inside the experimental chamber. 
	NOTE: The experimental chamber used here is a cubic acrylic box (0.45 m x 0.45 m x 0.45 m) designed to evaluate the amount and pattern of spontaneous motor activity26,27.</li>
	<li>Wait for 30 min before starting the recordings to ensure the animal is fully recovered from anesthesia. 
	NOTE: Isoflurane has a rapid onset and offset action which allows for rapid sedation and awakening28. Once the isoflurane supply is turned off, the animal will start to wake up. The animal is awake when it stays in the upright position and can ambulate freely in the experimental chamber without falling. This takes less than 15 min. To ensure the absence of any sedative effects, begin the recordings 30 min after the isoflurane is discontinued.</li>
	<li>Confirm the position of the microelectrode array implants postmortem by NISSL staining after fixing and sectioning the tissue29.</li>
</ol>

<ol>
	<li>Okano, H., Hikishima, K., Iriki, A., Sasaki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+common+marmoset+as+a+novel+animal+model+system+for+biomedical+and+neuroscience+research+applications.">The common marmoset as a novel animal model system for biomedical and neuroscience research applications.</a> Seminars in Fetal and Neonatal Medicine. 17 (6), 336-340 (2012).</li><li>Harris, R. 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=Evolutionary+genetics+and+implications+of+small+size+and+twinning+in+callitrichine+primates.">Evolutionary genetics and implications of small size and twinning in callitrichine primates.</a> Proceedings of the National Academy of Sciences. 111 (4), 1467-1472 (2014).</li><li>Kishi, N., Sato, K., Sasaki, E., Okano, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Common+marmoset+as+a+new+model+animal+for+neuroscience+research+and+genome+editing+technology.">Common marmoset as a new model animal for neuroscience research and genome editing technology.</a> Development, Growth &amp; Differentiation. 56 (1), 53-62 (2014).</li><li>Sasaki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospects+for+genetically+modified+non-human+primate+models,+including+the+common+marmoset.">Prospects for genetically modified non-human primate models, including the common marmoset.</a> Neuroscience Research. 93, 110-115 (2015).</li><li>Sasaki, E., 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=Generation+of+transgenic+non-human+primates+with+germline+transmission.">Generation of transgenic non-human primates with germline transmission.</a> Nature. 459 (7246), 523-527 (2009).</li><li>Sasaki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Creating+Genetically+Modified+Marmosets.">Creating Genetically Modified Marmosets.</a> The Common Marmoset in Captivity and Biomedical Research. , 335-353 (2019).</li><li>Sato, K., 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=Generation+of+a+Nonhuman+Primate+Model+of+Severe+Combined+Immunodeficiency+Using+Highly+Efficient+Genome+Editing.">Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.</a> Cell Stem Cell. 19 (1), 127-138 (2016).</li><li>Sato, K., 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=Resequencing+of+the+common+marmoset+genome+improves+genome+assemblies+and+gene-coding+sequence+analysis.">Resequencing of the common marmoset genome improves genome assemblies and gene-coding sequence analysis.</a> Scientific Reports. 5, 16894 (2015).</li><li>Chaplin, T. A., Yu, H. H., Soares, J. G. M., Gattass, R., Rosa, M. G. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Conserved+Pattern+of+Differential+Expansion+of+Cortical+Areas+in+Simian+Primates.">A Conserved Pattern of Differential Expansion of Cortical Areas in Simian Primates.</a> Journal of Neuroscience. 33 (38), 15120-15125 (2013).</li><li>Mitchell, J. F., Leopold, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+marmoset+monkey+as+a+model+for+visual+neuroscience.">The marmoset monkey as a model for visual neuroscience.</a> Neuroscience Research. 93, 20-46 (2015).</li><li>Brok, H. P. 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=Non-human+primate+models+of+multiple+sclerosis:+Non-human+primate+models+of+MS.">Non-human primate models of multiple sclerosis: Non-human primate models of MS.</a> Immunological Reviews. 183 (1), 173-185 (2001).</li><li>Santana, M. B., 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=Spinal+Cord+Stimulation+Alleviates+Motor+Deficits+in+a+Primate+Model+of+Parkinson's+disease.">Spinal Cord Stimulation Alleviates Motor Deficits in a Primate Model of Parkinson's disease.</a> Neuron. 84 (4), 716-722 (2014).</li><li>MacDougall, 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=Optogenetic+manipulation+of+neural+circuits+in+awake+marmosets.">Optogenetic manipulation of neural circuits in awake marmosets.</a> Journal of Neurophysiology. 116 (3), 1286-1294 (2016).</li><li>Wakabayashi, 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=Development+of+stereotaxic+recording+system+for+awake+marmosets+(Callithrix+jacchus).">Development of stereotaxic recording system for awake marmosets (Callithrix jacchus).</a> Neuroscience Research. 135, 37-45 (2018).</li><li>Johnston, K. D., Barker, K., Schaeffer, L., Schaeffer, D., Everling, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methods+for+chair+restraint+and+training+of+the+common+marmoset+on+oculomotor+tasks.">Methods for chair restraint and training of the common marmoset on oculomotor tasks.</a> Journal of Neurophysiology. 119 (5), 1636-1646 (2018).</li><li>Sedaghat-Nejad, E., 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=Behavioral+training+of+marmosets+and+electrophysiological+recording+from+the+cerebellum.">Behavioral training of marmosets and electrophysiological recording from the cerebellum.</a> Journal of Neurophysiology. , (2019).</li><li>Kringelbach, M. L., Owen, S. L., Aziz, T. Z. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Deep-brain+stimulation.">Deep-brain stimulation.</a> Future Neurology. 2 (6), 633-646 (2007).</li><li>Talakoub, O., Gomez Palacio Schjetnan, A., Valiante, T. A., Popovic, M. R., Hoffman, K. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Closed-Loop+Interruption+of+Hippocampal+Ripples+through+Fornix+Stimulation+in+the+Non-Human+Primate.">Closed-Loop Interruption of Hippocampal Ripples through Fornix Stimulation in the Non-Human Primate.</a> Brain Stimulation. 9 (6), 911-918 (2016).</li><li>Oddo, M., Hutchinson, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+and+monitoring+brain+injury:+the+role+of+cerebral+microdialysis.">Understanding and monitoring brain injury: the role of cerebral microdialysis.</a> Intensive Care Medicine. 44 (11), 1945-1948 (2018).</li><li>Metz, G. A., Whishaw, I. Q. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cortical+and+subcortical+lesions+impair+skilled+walking+in+the+ladder+rung+walking+test:+a+new+task+to+evaluate+fore-+and+hindlimb+stepping,+placing,+and+co-ordination.">Cortical and subcortical lesions impair skilled walking in the ladder rung walking test: a new task to evaluate fore- and hindlimb stepping, placing, and co-ordination.</a> Journal of Neuroscience Methods. 115 (2), 169-179 (2002).</li><li>Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, J. M., Deisseroth, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optical+Deconstruction+of+Parkinsonian+Neural+Circuitry.">Optical Deconstruction of Parkinsonian Neural Circuitry.</a> Science. 324, 354-359 (2009).</li><li>Hammer, D. X., 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=Longitudinal+vascular+dynamics+following+cranial+window+and+electrode+implantation+measured+with+speckle+variance+optical+coherence+angiography.">Longitudinal vascular dynamics following cranial window and electrode implantation measured with speckle variance optical coherence angiography.</a> Biomedical Optics Express. 5 (8), 2823-2836 (2014).</li><li>Komatsu, M., Kaneko, T., Okano, H., Ichinohe, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+Implantation+of+Whole-cortical+Electrocorticographic+Array+in+the+Common+Marmoset.">Chronic Implantation of Whole-cortical Electrocorticographic Array in the Common Marmoset.</a> Journal of Visualized Experiments. (144), (2019).</li><li>Oliveira, L. M. O., Dimitrov, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Surgical Techniques for Chronic Implantation of Microwire Arrays in Rodents and Primates. , (2008).</li><li>Santana, M. B., 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=Spinal+Cord+Stimulation+Alleviates+Motor+Deficits+in+a+Primate+Model+of+Parkinson's+disease.">Spinal Cord Stimulation Alleviates Motor Deficits in a Primate Model of Parkinson's disease.</a> Neuron. 84 (4), 716-722 (2014).</li><li>Santana, M., Palm&#233;r, T., Simpl&#237;cio, H., Fuentes, R., Petersson, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+long-term+motor+deficits+in+the+6-OHDA+model+of+Parkinson's+disease+in+the+common+marmoset.">Characterization of long-term motor deficits in the 6-OHDA model of Parkinson's disease in the common marmoset.</a> Behavioural Brain Research. 290, 90-101 (2015).</li><li>Misra, S., Koshy, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+the+practice+of+sedation+with+inhalational+anaesthetics+in+the+intensive+care+unit+with+the+AnaConDa+device.">A review of the practice of sedation with inhalational anaesthetics in the intensive care unit with the AnaConDa device.</a> Indian Journal of Anaesthesia. 56 (6), 518-523 (2012).</li><li>Freire, M. A. 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=Distribution+and+Morphology+of+Calcium-Binding+Proteins+Immunoreactive+Neurons+following+Chronic+Tungsten+Multielectrode+Implants.">Distribution and Morphology of Calcium-Binding Proteins Immunoreactive Neurons following Chronic Tungsten Multielectrode Implants.</a> PLOS ONE. 10 (6), 0130354 (2015).</li><li>Budoff, S., 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=Astrocytic+Response+to+Acutely-+and+Chronically+Implanted+Microelectrode+Arrays+in+the+Marmoset+(Callithrix+jacchus)+Brain.">Astrocytic Response to Acutely- and Chronically Implanted Microelectrode Arrays in the Marmoset (Callithrix jacchus) Brain.</a> Brain Sciences. 9 (2), 19 (2019).</li><li>Dzirasa, K., Fuentes, R., Kumar, S., Potes, J. M., Nicolelis, M. A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chronic+in+vivo+multi-circuit+neurophysiological+recordings+in+mice.">Chronic in vivo multi-circuit neurophysiological recordings in mice.</a> Journal of Neuroscience Methods. 195 (1), 36-46 (2011).</li><li>Nicolelis, M. A. L., 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=Chronic,+multisite,+multielectrode+recordings+in+macaque+monkeys.">Chronic, multisite, multielectrode recordings in macaque monkeys.</a> Proceedings of the National Academy of Sciences. 100 (19), 11041-11046 (2003).</li><li>Lehew, G., Nicolelis, M. A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> State-of-the-Art Microwire Array Design for Chronic Neural Recordings in Behaving Animals. , (2008).</li><li>Paxinos, G., Watson, C., Petrides, M., Rosa, M., Tokuno, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> The Marmoset Brain in Stereotaxic Coordinates. , (2012).</li><li>Brown, M. J., Pearson, P. T., Tomson, F. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+animal+surgery+in+research+and+teaching.">Guidelines for animal surgery in research and teaching.</a> American Journal of Veterinary Research. 54 (9), 1544-1559 (1993).</li><li>Flecknell, P. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anaesthesia+of+Animals+for+Biomedical+Research.">Anaesthesia of Animals for Biomedical Research.</a> British Journal of Anaesthesia. 71 (6), 885-894 (1993).</li><li>Kurihara, S., 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+Surgical+Procedure+for+the+Administration+of+Drugs+to+the+Inner+Ear+in+a+Non-Human+Primate+Common+Marmoset+(Callithrix+jacchus).">A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset (Callithrix jacchus).</a> Journal of Visualized Experiments. (132), (2018).</li><li>Boer, R. A., de Vries, A. M. O., Louwerse, A. L., Sterck, E. H. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+behavioral+context+of+visual+displays+in+common+marmosets+(Callithrix+jacchus).">The behavioral context of visual displays in common marmosets (Callithrix jacchus).</a> American Journal of Primatology. 75 (11), 1084-1095 (2013).</li><li>Kudo, C., Nozari, A., Moskowitz, M. A., Ayata, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+impact+of+anesthetics+and+hyperoxia+on+cortical+spreading+depression.">The impact of anesthetics and hyperoxia on cortical spreading depression.</a> Experimental Neurology. 212 (1), 201-206 (2008).</li><li>Ghomashchi, 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=A+low-cost,+open-source,+wireless+electrophysiology+system.">A low-cost, open-source, wireless electrophysiology system.</a> 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society. , 3138-3141 (2014).</li><li>Fu, T. M., Hong, G., Viveros, R. D., Zhou, T., Lieber, C. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Highly+scalable+multichannel+mesh+electronics+for+stable+chronic+brain+electrophysiology.">Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology.</a> Proceedings of the National Academy of Sciences. 114 (47), 10046-10055 (2017).</li></ol>

The authors have nothing to disclose.

This work provides a detailed description of the procedures involved in the implantation of microelectrode recording arrays in the marmoset brain. This same protocol can be readily used when implanting electrodes, whether homemade or commercially available, in other small primates. Additionally, it can be easily adapted for other experimental ends that require precise targeting of brain structures. Therefore, this protocol is purposefully vague regarding stereotaxic coordinates and cranial drilling techniques, because th...

Common marmosets (Callithrix jacchus) are gaining recognition as an important model organism in many fields of research, including neuroscience. These new-world primates represent an important complementary animal model to both rodents and other non-human primates (NHPs), such as the rhesus macaque. Like rodents, these animals are small, easy to manipulate, and relatively economical to care for and breed1,2,3,4, as compared with larger NHPs. Furthermore, these animals have a propensity for twinning and high fecundity relative to other NHPs1,2,3. Another advantage the marmoset has over many other primates is that modern molecular biology tools3,4,5,6,7 and a sequenced genome2,3,4,5,8 have been used to genetically modify them. Both knock-in animals using lentivirus5, and knock-out animals using zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENS)7, have yielded viable founder animals.
An advantage in relation to rodents is that marmosets, as primates, are phylogenetically closer to humans3,5,6,9,10,11. Like humans, marmosets are diurnal animals that depend on a highly developed visual system to guide much of their behavior10. Further, marmosets exhibit behavioral complexity, including a wide range of social behaviors such as the use of different vocalizations3, allowing researchers to address questions not possible in other species. From a neuroscientific perspective, marmosets have lissencephaly brains, unlike the more commonly used rhesus macaque9. Furthermore, marmosets have a central nervous system similar to humans, including a more highly developed prefrontal cortex9. Together, all these characteristics position marmosets as a valuable model to study brain function in health and disease.
A common method for studying brain function involves implanting electrodes in anatomically specific locations by means of stereotaxic neurosurgery. This allows for chronical recording of the neural activity in different target areas in awake and freely behaving animals12,13. Stereotaxic neurosurgery is an indispensable technique used in many lines of research, as it allows precise targeting of neuroanatomical regions. Compared to macaque and rodent literature, there are fewer published studies describing the stereotaxic neurosurgery specific to the marmoset, and they tend to provide sparse detail of the steps involved in the surgery. Moreover, those with greater detail mainly focus on procedures for electrophysiology recording in head-restrained animals14,15,16,17.
In order to facilitate wider adoption of marmosets as a model organism in neuroscience research, the present method defines specific steps necessary for a successful stereotaxic neurosurgery in this species. In addition to implantation of recording arrays, as detailed in the present method, the same technique can be adapted for many other experimental ends, including implantation of stimulating electrodes for the treatment of diseases18 or causally driving circuit behavior19; implantation of guide cannulas for extraction and quantification of neurotransmitters20, injections of reagents, including those for inducing disease models12 or for circuit tracing studies15; ablation of discrete tissue regions21; implantation of optrodes for optogenetic studies22; implantation of optical windows for cortical microscopic analysis23; and implantation of electrocorticographic (ECoG) arrays24. Thus, the overall goal of this procedure is to outline the surgical steps involved in the implantation of microelectrode arrays for chronic electrophysiological recordings in freely behaving marmosets.

<table><tbody><tr><td>&lt;strong&gt;Equipments&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>683 Small Animal Ventilator</td><td>Harvard Apparatus, Inc.</td><td>55-0000</td><td></td></tr><tr><td>Anesthesia Assembly</td><td>BRASMED</td><td>COLIBRI</td><td></td></tr><tr><td>Barber Clippers</td><td>Mundial</td><td>HC-SERIES</td><td></td></tr><tr><td>Dental Drill</td><td>Norgen</td><td>B07-201-M1KG</td><td></td></tr><tr><td>Homeothermic Heating Pad and Monitor</td><td>Harvard Apparatus, Inc.</td><td>50-7212</td><td></td></tr><tr><td>Marmoset Stereotaxic Frame</td><td>Narishige Scientific Instrument Lab</td><td>SR-6C-HT</td><td></td></tr><tr><td>Patient Monitor and Pulse Oximeter</td><td>Bionet Co., Ltd</td><td>BM3</td><td></td></tr><tr><td>Stereotaxic Micromanipulator</td><td>Narishige Scientific Instrument Lab</td><td>SM-15R</td><td></td></tr><tr><td>Surgical Microscope</td><td>Opto</td><td>SM PLUS IBZ</td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>&lt;strong&gt;Instruments&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>Allis tissue forceps</td><td>Sklar</td><td>36-2275</td><td></td></tr><tr><td>Alm Retractor, rounded point, 4x4 teeth</td><td>Rhosse</td><td>RH11078</td><td></td></tr><tr><td>Angled McPherson Forceps</td><td>Oftalmologiabr</td><td>11301A</td><td></td></tr><tr><td>Curved Surgial Scissors</td><td>Harvard Apparatus, Inc.</td><td>72-8422</td><td></td></tr><tr><td>Curved Tissue Forceps</td><td>Sklar</td><td>47-1186</td><td></td></tr><tr><td>Delicate Dissection forceps</td><td>WPI</td><td>WP5015</td><td></td></tr><tr><td>Dental Drill Bit</td><td>Microdont</td><td>ISO.806.314.001.524.010</td><td></td></tr><tr><td>Essring Tissue Forceps</td><td>Sklar</td><td>19-2460</td><td></td></tr><tr><td>FG 1/4 Dental Drill Bit</td><td>Microdont</td><td>ISO.700.314.001.006.005</td><td></td></tr><tr><td>Halsey Needle Holder</td><td>WPI</td><td>15926-G</td><td></td></tr><tr><td>Halstead Mosquito forceps</td><td>WPI</td><td>503724-12</td><td></td></tr><tr><td>Hemostatic Forceps, Straight</td><td>Sklar</td><td>17-1260</td><td></td></tr><tr><td>Jewler Forceps</td><td>Sklar</td><td>66-7436</td><td></td></tr><tr><td>McPherson-Vannas Optathalmic microscissor, 3 mm point</td><td>Argos Instrumental</td><td>ARGOS-4004</td><td></td></tr><tr><td>Pereosteal Raspatory</td><td>Golgran</td><td>38-1</td><td></td></tr><tr><td>Scalpal Handle</td><td>Harvard Apparatus, Inc.</td><td>72-8354</td><td></td></tr><tr><td>Screwdrivers</td><td>Eurotool</td><td>SCR-830.00</td><td></td></tr><tr><td>Sodering Iron</td><td>Hikari</td><td>21K006</td><td></td></tr><tr><td>Surgical Scissor</td><td>Harvard Apparatus, Inc.</td><td>72-8400</td><td></td></tr><tr><td>Toothed forceps</td><td>WPI</td><td>501266-G</td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>&lt;strong&gt;Disposables/Single Use&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>1 ml sterile syringe with 26 G needle</td><td>Descarpack</td><td>7898283812785</td><td></td></tr><tr><td>130 cm x 140 cm surgical field, presterilized</td><td>ProtDesc</td><td>7898467276344</td><td></td></tr><tr><td>24G Needle, presterilized</td><td>Descarpack</td><td>7898283812846</td><td></td></tr><tr><td>50 cm x 50 cm surgical field, presterilized</td><td>Esterili-med</td><td>110100236</td><td></td></tr><tr><td>Cotton Tipped Probes, Presterilized</td><td>Jiangsu Suyun Medical Materials Co. LTD</td><td>23007</td><td></td></tr><tr><td>Cotton tipped Qutips</td><td>Higie Topp</td><td>7898095296063</td><td></td></tr><tr><td>Electrode Array</td><td></td><td></td><td>Home made</td></tr><tr><td>Endotracheal tube without cuff, internal diameter 2.0 mm, outer diameter 2.9 mm</td><td>Solidor</td><td>7898913077201</td><td></td></tr><tr><td>Tinned copper wire, 0.15 mm diameter</td><td></td><td></td><td></td></tr><tr><td>M1.4x3 Stainless steel screws</td><td>USMICROSCREW</td><td>M14-30M-SS-P</td><td></td></tr><tr><td>Medical Tape</td><td>Missner</td><td>7896544910102</td><td></td></tr><tr><td>Nylon surgical sutures</td><td>Shalon</td><td>N540CTI25</td><td></td></tr><tr><td>Scalpal Blade, presterilized</td><td>AdvantiVe</td><td>1037</td><td></td></tr><tr><td>solder</td><td>Kester</td><td>SN63PB37</td><td></td></tr><tr><td>Sterile Saline 0.9%</td><td>Isofarma</td><td>7898361700041</td><td></td></tr><tr><td>Sterile Surgical Gloves</td><td>Maxitex</td><td>7898949349051</td><td></td></tr><tr><td>Sterile Surgical Gown</td><td>ProtDesc</td><td>7898467281208</td><td></td></tr><tr><td>Surgical Gauze, 15 cm x 26 cm presterilized</td><td>H&amp;eacute;ika</td><td>7898488470315</td><td></td></tr><tr><td>Gelfoam</td><td>Pfizer</td><td></td><td></td></tr><tr><td></td><td></td><td></td><td></td></tr><tr><td>&lt;strong&gt;Drugs/Chemicals&lt;/strong&gt;</td><td></td><td></td><td></td></tr><tr><td>0.25mg/ml Atropine</td><td>Isofarma</td><td></td><td></td></tr><tr><td>10% Lidocaine Spray</td><td>Produtos Qu&amp;iacute;micos Farmac&amp;ecirc;uticos Ltda.</td><td>7896676405644</td><td></td></tr><tr><td>2.5% Enrofloxacino veterinary antibiotic</td><td>Chemitec</td><td>0137-02</td><td></td></tr><tr><td>Dexametasona Veterinary Anti inflammatory</td><td>MSD</td><td>R06177091A-00-15</td><td></td></tr><tr><td>Hydrogen Peroxide</td><td>Farmax</td><td>7896902211537</td><td></td></tr><tr><td>Isoflourane</td><td>BioChimico</td><td>7897406113068</td><td></td></tr><tr><td>Jet Acrylic polymerization solution</td><td>Artigos Odontol&amp;oacute;gicos Cl&amp;aacute;ssico</td><td></td><td></td></tr><tr><td>Jet Auto Polymerizing Acrylic</td><td>Artigos Odontol&amp;oacute;gicos Cl&amp;aacute;ssico</td><td></td><td></td></tr><tr><td>Ketamine 10%</td><td>Syntec</td><td></td><td></td></tr><tr><td>Lidocaine and Phenylephrine 1.8 ml local anesthetic</td><td>SS White</td><td>7892525041049</td><td></td></tr><tr><td>Povidone-Iodine solutiom</td><td>Farmax</td><td>7896902234093</td><td></td></tr><tr><td>Riohex 2% surgical Soap</td><td>Rioqu&amp;iacute;mica</td><td>7897780209418</td><td></td></tr><tr><td>Silver Paint</td><td>SPI Supplies</td><td>05002-AB</td><td></td></tr><tr><td>Tramadol chloride 50 mg/ml</td><td>Uni&amp;atilde;o Qu&amp;iacute;mica</td><td>7896006245452</td><td></td></tr><tr><td>Refresh gel (polyacrylic acid)</td><td>Allergan</td><td></td><td></td></tr></tbody></table>

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.

The purpose of this study was to describe a stereotaxic neurosurgical procedure for implantation of microelectrode arrays for electrophysiological recordings in the common marmoset. A typical surgery (from anesthesia induction to anesthesia recovery) will last for approximately 5&#8722;7 h, depending on the number of arrays implanted. Here, two arrays were symmetrically implanted, one in each brain hemisphere. Each array contained 32 stainless steel microwires arranged in seven bundles targeting several structures of the...

Watch this Scientific Journal Video about Stereotaxic Surgery for Implantation of Microelectrode Arrays in the Common Marmoset Callithrix jacchus at JoVE.com

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).

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 ...

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Neuroscience

9.3K Views.  Santos Dumont Institute. Het algemene doel van deze procedure is om de chirurgische stappen die betrokken zijn bij de implantatie van micro-elektrodonderrode arrays voor chronische elektrofysiologische opname in vrij gedragen marmosets schetsen. Marmosets zijn kleine primaten die steeds vaker worden gebruikt in neurowetenschappelijk onderzoek. Deze dieren delen veel van de praktische en logistieke voordelen van knaagdieren.Hun neiging tot jumelage en hoge fecunditeit op jonge leeftijd betekent klaar toegang to...

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

Simultaneous fMRI and Electrophysiology in the Rodent Brain

To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in which functional MRI data and in vivo intracortical recording can be performed simultaneously. The combination of MRI and electrical recording is technically challenging because the electrodes used for recording distort the MRI images and the MRI acquisition induces noise in the electrical recording. To minimize the mutual interference of the two modalities, glass microelectrodes were used rather than metal and a noise removal algorithm was implemented for the electrophysiology data. In our studies, two microelectrodes were separately implanted in bilateral primary somatosensory cortices (SI) of the rat and fixed in place. One coronal slice covering the electrode tips was selected for functional MRI. Electrode shafts and fixation positions were not included in the image slice to avoid imaging artifacts. The removed scalp was replaced with toothpaste to reduce susceptibility mismatch and prevent Gibbs ringing artifacts in the images. The artifact structure induced in the electrical recordings by the rapidly-switching magnetic fields during image acquisition was characterized by averaging all cycles of scans for each run. The noise structure during imaging was then subtracted from original recordings. The denoised time courses were then used for further analysis in combination with the fMRI data. As an example, the simultaneous acquisition was used to determine the relationship between spontaneous fMRI BOLD signals and band-limited intracortical electrical activity. Simultaneous fMRI and electrophysiological recording in the rodent will provide a platform for many exciting applications in neuroscience in addition to elucidating the relationship between the fMRI BOLD signal and neuronal activity.

We have developed a method for simultaneous functional magnetic resonance imaging and electrophysiological recording in the rodent brain, providing a platform for the investigation of the relationship between neural activity and the blood oxygenation level dependent (BOLD) MRI signal.

To examine the neural basis of the blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) signal, we have developed a rodent model in ...

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

Deep Brain Stimulation with Simultaneous fMRI in Rodents

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to image rodents with simultaneous DBS. DBS fMRI presents a number of technical challenges, including accuracy of electrode implantation, MR artifacts created by the electrode, choice of anesthesia and paralytic to minimize any neuronal effects while simultaneously eliminating animal motion, and maintenance of physiological parameters, deviation from which can confound the BOLD signal.&#160;Our laboratory has developed a set of procedures that are capable of overcoming most of these possible issues. For electrical stimulation, a homemade tungsten bipolar microelectrode is used, inserted stereotactically at the stimulation site in the anesthetized subject. In preparation for imaging, rodents are fixed on a plastic headpiece and transferred to the magnet bore. For sedation and paralysis during scanning, a cocktail of dexmedetomidine and pancuronium is continuously infused, along with a minimal dose of isoflurane; this preparation minimizes the BOLD ceiling effect of volatile anesthetics. In this example experiment, stimulation of the subthalamic nucleus (STN) produces BOLD responses which are observed primarily in ipsilateral cortical regions, centered in motor cortex. Simultaneous DBS and fMRI allows the unambiguous modulation of neural circuits dependent on stimulation location and stimulation parameters, and permits observation of neuronal modulations free of regional bias. This technique may be used to explore the downstream effects of modulating neural circuitry at nearly any brain region, with implications for both experimental and clinical DBS.

This protocol describes a standard method for simultaneous functional magnetic resonance imaging and deep brain stimulation in the rodent. The combined use of these experimental tools allows for the exploration of global downstream activity in response to electrical stimulation at virtually any brain target.

In order to visualize the global and downstream neuronal responses to deep brain stimulation (DBS) at various targets, we have developed a protocol for ...

Non-restraining EEG Radiotelemetry: Epidural and Deep Intracerebral Stereotaxic EEG Electrode Placement

Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and neurodegenerative diseases as well as epilepsies. This powerful technique does not only provide valuable insights into the underlying pathophysiological mechanisms, i.e., the etiopathogenesis of CNS related diseases, it also facilitates the development of new translational, i.e., therapeutic approaches. Whereas competing techniques that make use of recorder systems used in jackets or tethered systems suffer from their unphysiological restraining to semi-restraining character, radiotelemetric EEG recordings overcome these disadvantages. Technically, implantable EEG radiotelemetry allows for precise and highly sensitive measurement of epidural and deep, intracerebral EEGs under various physiological and pathophysiological conditions. First, we present a detailed protocol of a straight forward, successful, quick and efficient technique for epidural (surface) EEG recordings resulting in high-quality electrocorticograms. Second, we demonstrate how to implant deep, intracerebral EEG electrodes, e.g., in the hippocampus (electrohippocampogram). For both approaches, a computerized 3D stereotaxic electrode implantation system is used. The radiofrequency transmitter itself is implanted into a subcutaneous pouch in both mice and rats. Special attention also has to be paid to pre-, peri- and postoperative treatment of the experimental animals. Preoperative preparation of mice and rats, suitable anesthesia as well as postoperative treatment and pain management are described in detail.

Non-restraining EEG radiotelemetry is a valuable methodological approach to record in vivo long-term electroencephalograms from freely moving rodents. This detailed protocol describes stereotaxic epidural and deep intracerebral electrode placement in different brain regions in order to obtain reliable recordings of CNS rhythmicity and CNS related behavioral stages.

Implantable EEG radiotelemetry is of central relevance in the neurological characterization of transgenic mouse models of neuropsychiatric and ...

A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset (Callithrix jacchus)

Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset. We adopted posterior tympanotomy, a procedure used clinically in human surgery, to avoid manipulation of the tympanic membrane that may cause conductive hearing loss. This surgical procedure did not lead to any significant hearing loss. This approach was possible due to the large bulla structure of the common marmoset, although the lateral semicircular canal and vertical portion of the facial nerve should be carefully considered. This surgical method allows us to perform the safe and accurate administration of drugs without hearing loss, which is of great importance in obtaining pre-clinical proof of concept for translational research.

A Surgical Procedure for the Administration of Drugs to the Inner Ear in a Non-Human Primate Common Marmoset Callithrix jacchus

We report a surgical method to administrate drugs to the inner ear of a non-human primate, the common marmoset (Callithrix jacchus), via the round window membrane.

Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset ...

Medicine

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.

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. ...

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 ...

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 ...

Development of an X-Y Electrode Stage for Precise Neural Recording in Marmosets

Electrophysiology of Laminar Cortical Activity in the Common Marmoset

The marmoset monkey provides an ideal model for examining laminar cortical circuits due to its smooth cortical surface, which facilitates recordings with linear arrays. The marmoset has recently grown in popularity due to its similar neural functional organization to other primates and its technical advantages for recording and imaging. However, neurophysiology in this model poses some unique challenges due to the small size and lack of gyri as anatomical landmarks. Using custom-built micro-drives, researchers can manipulate linear array placement to sub-millimeter precision and reliably record at the same retinotopically targeted location across recording days. This protocol describes the step-by-step construction of the micro-drive positioning system and the neurophysiological recording technique with silicon linear electrode arrays. With precise control of electrode placement across recording sessions, researchers can easily traverse the cortex to identify areas of interest based on their retinotopic organization and the tuning properties of the recorded neurons. Further, using this laminar array electrode system, it is possible to apply a current source density analysis (CSD) to determine the recording depth of individual neurons. This protocol also demonstrates examples of laminar recordings, including spike waveforms isolated in Kilosort, which span multiple channels on the arrays.

Author Spotlight: Optimizing Micro-Drive Systems for Precise Electrode Positioning in Marmoset

Custom-built micro-drives enable the sub-millimeter targeting of cortical recording sites with linear silicon arrays.

The marmoset monkey provides an ideal model for examining laminar cortical circuits due to its smooth cortical surface, which facilitates recordings with ...

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

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