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

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

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

Invasive Computational Psychiatry.

Computational psychiatry, a relatively new yet prolific field that aims to understand psychiatric disorders with formal theories about the brain, has seen tremendous growth in the past decade. Despite initial excitement, actual progress made by computational psychiatry seems stagnant. Meanwhile, understanding of the human brain has benefited tremendously from recent progress in intracranial neuroscience. Specifically, invasive techniques such as stereotactic electroencephalography, electrocorticography, and deep brain stimulation have provided a unique opportunity to precisely measure and causally modulate neurophysiological activity in the living human brain. In this review, we summarize progress and drawbacks in both computational psychiatry and invasive electrophysiology and propose that their combination presents a highly promising new direction-invasive computational psychiatry. The value of this approach is at least twofold. First, it advances our mechanistic understanding of the neural computations of mental states by providing a spatiotemporally precise depiction of neural activity that is traditionally unattainable using noninvasive techniques with human subjects. Second, it offers a direct and immediate way to modulate brain states through stimulation of algorithmically defined neural regions and circuits (i.e., algorithmic targeting), thus providing both causal and therapeutic insights. We then present depression as a use case where the combination of computational and invasive approaches has already shown initial success. We conclude by outlining future directions as a road map for this exciting new field as well as presenting cautions about issues such as ethical concerns and generalizability of findings.

A Multimodal Multi-Shank Fluorescence Neural Probe for Cell-Type-Specific Electrophysiology in Multiple Regions across a Neural Circuit.

Cell-type-specific, activity-dependent electrophysiology can allow in-depth analysis of functional connectivity inside complex neural circuits composed of various cell types. To date, optics-based fluorescence recording devices enable monitoring cell-type-specific activities. However, the monitoring is typically limited to a single brain region, and the temporal resolution is significantly low. Herein, a multimodal multi-shank fluorescence neural probe that allows cell-type-specific electrophysiology from multiple deep-brain regions at a high spatiotemporal resolution is presented. A photodiode and an electrode-array pair are monolithically integrated on each tip of a minimal-form-factor silicon device. Both fluorescence and electrical signals are successfully measured simultaneously in GCaMP6f expressing mice, and the cell type from sorted neural spikes is identified. The probe's capability of combined electro-optical recordings for cell-type-specific electrophysiology at multiple brain regions within a neural circuit is demonstrated. The new experimental paradigm to enable the precise investigation of functional connectivity inside and across complex neural circuits composed of various cell types is expected.

Protocol for remapping of place cells in disease mouse models.

Hippocampal place cells and entorhinal grid cells exhibit distinct spike patterns in different environments called "remapping," and we have recently shown that remapping of place cells becomes disrupted in a mouse model of Alzheimer's disease. Here, we describe our protocol for investigating remapping of place cells and grid cells using a custom-made electrophysiology device, with detailed descriptions and problem-solving tips for the construction and implantation of the recording device. We also provide steps for behavioral training, recording, and data analysis. For complete details on the use and execution of this protocol, please refer to Jun et al. (2020).

Electrode pooling can boost the yield of extracellular recordings with switchable silicon probes.

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.

Ultra-conformal skin electrodes with synergistically enhanced conductivity for long-time and low-motion artifact epidermal electrophysiology.

Accurate and imperceptible monitoring of electrophysiological signals is of primary importance for wearable healthcare. Stiff and bulky pregelled electrodes are now commonly used in clinical diagnosis, causing severe discomfort to users for long-time using as well as artifact signals in motion. Here, we report a ~100 nm ultra-thin dry epidermal electrode that is able to conformably adhere to skin and accurately measure electrophysiological signals. It showed low sheet resistance (~24 Ω/sq, 4142 S/cm), high transparency, and mechano-electrical stability. The enhanced optoelectronic performance was due to the synergistic effect between graphene and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS), which induced a high degree of molecular ordering on PEDOT and charge transfer on graphene by strong π-π interaction. Together with ultra-thin nature, this dry epidermal electrode is able to accurately monitor electrophysiological signals such as facial skin and brain activity with low-motion artifact, enabling human-machine interfacing and long-time mental/physical health monitoring.

A Stretchable and Transparent Electrode Based on PEGylated Silk Fibroin for In Vivo Dual-Modal Neural-Vascular Activity Probing.

Transparent electrodes that form seamless contact and enable optical interrogation at the electrode-brain interface are potentially of high significance for neuroscience studies. Silk hydrogels can offer an ideal platform for transparent neural interfaces owing to their superior biocompatibility. However, conventional silk hydrogels are too weak and have difficulties integrating with highly conductive and stretchable electronics. Here, a transparent and stretchable hydrogel electrode based on poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) and PEGylated silk protein is reported. PEGylated silk protein with poly(ethylene glycol) diglycidyl ether (PEGDE) improves the Young's modulus to 1.51-10.73 MPa and the stretchability to ≈400% from conventional silk hydrogels (<10 kPa). The PEGylated silk also helps form a robust interface with PEDOT:PSS thin film, making the hydrogel electrode synergistically incorporate superior stretchability (≈260%), stable electrical performance (≈4 months), and a low sheet resistance (≈160 ± 56 Ω sq-1 ). Finally, the electrode facilitates efficient electrical recording, and stimulation with unobstructed optical interrogation and rat-brain imaging are demonstrated. The highly transparent and stretchable hydrogel electrode offers a practical tool for neuroscience and paves the way for a harmonized tissue-electrode interface.

Effect of creatine and sildenafil citrate on the physical performance of mice / Efecto de la creatina y del citrato de sildenafil sobre el desempeño físico de ratones / Efeito da creatina e do citrato de sildenafila sobre o desempenho físico de camundongos

ABSTRACT Introduction: The use of substances to enhance sports performance among professional and amateur athletes is increasing. Such substances may either be included in the group of dietary supplements or fall into pharmacological classes. Every substance used for this purpose is called an ergogenic agent. The number of ergogenic options available increases every day, favoring overuse and use without proper guidance. Among the dietary supplements, we highlight the use of creatine, a substance widespread in sports. Among the pharmacological groups, many drugs are used. Recently the use of sildenafil citrate by professional athletes from various predominantly aerobic sports modalities was reported in the media. Objective: To compare and demonstrate the responses caused by physical training associated with the use of creatine and sildenafil citrate in mice. Methods: A swim training protocol was applied and then an electrophysiograph was used in order to obtain parameters related to contraction intensity, the area under the curve and the percentage drop. Results: The responses obtained demonstrated the ergogenic action of creatine because it altered the parameters used for measurement. The use of sildenafil citrate did not yield satisfactory results to frame the drug as an ergogenic agent. Conclusion: Creatine has an ergogenic effect, reducing the percentage drop after 10 seconds, while sildenafil demonstrated no ergogenic potential and, interestingly, resulted in weaker responses when compared to the exercise groups. Evidence level II; Comparative prospective study .

RESUMEN Introducción: El uso de sustancias con el objetivo de aumentar el rendimiento deportivo entre atletas profesionales y amateurs es creciente. Tales sustancias pueden formar parte del grupo de suplementos alimentarios o integrar clases farmacológicas. Toda sustancia empleada para ese fin es denominada agente ergogénico. El número de opciones entre los agentes ergogénicos aumenta cada día, favoreciendo así su uso excesivo y sin la debida orientación. Entre los suplementos alimentarios, se destaca el uso de creatina, sustancia muy difundida en el medio deportivo. Ya entre los grupos farmacológicos, muchas sustancias son usadas. Recientemente, fue divulgado entre los medios de comunicación el uso de citrato de sildenafil por atletas profesionales, de varias modalidades deportivas, predominantemente las aeróbicas. Objetivos: Comparar y demostrar las respuestas ocasionadas por el entrenamiento físico, asociadas al uso de creatina y citrato de sildenafil en ratones. Métodos: Se aplicó un protocolo de entrenamiento de natación y, a continuación, se usó un electrofisiógrafo con el objetivo de obtener parámetros referentes a la intensidad de contracción, al área bajo la curva y a la caída porcentual. Resultados: Las respuestas obtenidas demuestran acción ergogénica de la creatina, visto que alteraron los parámetros empleados para la medición. Ya el uso de citrato de sildenafil no presentó resultados satisfactorios para encuadrar al fármaco como agente ergogénico. Conclusión: La creatina presenta efecto ergogénico porque reduce la caída porcentual después de 10 segundos, mientras que el sildenafil no presentó potencial ergogénico y, curiosamente, demostró respuestas inferiores cuando comparado a los grupos de ejercicio. Nivel de evidencia II; Estudio prospectivo comparativo .

RESUMO Introdução: O uso de substâncias com o objetivo de aumentar o rendimento esportivo entre atletas profissionais e amadores é crescente. Tais substâncias podem fazer parte do grupo de suplementos alimentares ou integrar classes farmacológicas. Toda substância empregada para esse fim é denominada de agente ergogênico. O número de opções entre os agentes ergogênicos aumenta a cada dia, favorecendo assim o uso em demasia e sem a devida orientação. Entre os suplementos alimentares, salientamos a utilização de creatina, substância muito difundida no meio esportivo. Já entre os grupos farmacológicos, muitas substâncias são utilizadas. Recentemente, foi divulgado entre os meios de comunicação o uso de citrato de sildenafila por atletas profissionais de várias modalidades esportivas, predominantemente as aeróbicas. Objetivos: Comparar e demonstrar as repostas ocasionadas pelo treinamento físico, associadas ao uso de creatina e citrato de sildenafila em camundongos. Métodos: Aplicou-se um protocolo de treinamento de natação e, a seguir, empregou-se um eletrofisiógrafo com objetivo de obter parâmetros referentes à intensidade de contração, à área sob a curva e à queda percentual. Resultados: As respostas obtidas demonstram ação ergogênica da creatina, visto que alteraram os parâmetros empregados para a mensuração. Já a utilização de citrato de sildenafila não apresentou resultados satisfatórios para enquadrar o fármaco como agente ergogênico. Conclusão: A creatina apresenta efeito ergogênico porque reduz a queda percentual após 10 segundos, já a sildenafila não apresentou potencial ergogênico e, curiosamente, demonstrou respostas inferiores quando comparado aos grupos de exercício. Nível de evidência II; Estudo prospectivo comparativo .

Neuropixels 2.0: A miniaturized high-density probe for stable, long-term brain recordings.

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice.

Three-micrometer-diameter needle electrode with an amplifier for extracellular in vivo recordings.

Microscale needle-electrode devices offer neuronal signal recording capability in brain tissue; however, using needles of smaller geometry to minimize tissue damage causes degradation of electrical properties, including high electrical impedance and low signal-to-noise ratio (SNR) recording. We overcome these limitations using a device assembly technique that uses a single needle-topped amplifier package, called STACK, within a device of ∼1 × 1 mm2 Based on silicon (Si) growth technology, a <3-µm-tip-diameter, 400-µm-length needle electrode was fabricated on a Si block as the module. The high electrical impedance characteristics of the needle electrode were improved by stacking it on the other module of the amplifier. The STACK device exhibited a voltage gain of >0.98 (-0.175 dB), enabling recording of the local field potential and action potentials from the mouse brain in vivo with an improved SNR of 6.2. Additionally, the device allowed us to use a Bluetooth module to demonstrate wireless recording of these neuronal signals; the chronic experiment was also conducted using STACK-implanted mice.

A Morphable Ionic Electrode Based on Thermogel for Non-Invasive Hairy Plant Electrophysiology.

Plant electrophysiology lays the foundation for smart plant interrogation and intervention. However, plant trichomes with hair-like morphologies present topographical features that challenge stable and high-fidelity non-invasive electrophysiology, due to the inadequate dynamic shape adaptability of conventional electrodes. Here, this issue is overcome using a morphable ionic electrode based on a thermogel, which gradually transforms from a viscous liquid to a viscoelastic gel. This transformation enables the morphable electrode to lock into the abrupt hairy surface irregularities and establish a conformal and adhesive interface. It achieves down to one tenth of the impedance and 4-5 times the adhesive strengths of conventional hydrogel electrodes on hairy leaves. As a result of the improved electrical and mechanical robustness, the morphable electrode can record more than one order of magnitude higher signal-to-noise ratio on hairy plants and maintains high-fidelity recording despite plant movements, achieving superior performance to conventional hydrogel electrodes. The reported morphable electrode is a promising tool for hairy plant electrophysiology and may be applied to diversely textured plants for advanced sensing and modulation.

Electrophysiology on Channel-Forming Proteins in Artificial Lipid Bilayers: Next-Generation Instrumentation for Multiple Recordings in Parallel.

Artificial lipid bilayers have been used for several decades to study channel-forming pores and ion channels in membranes. Until recently, the classical two-chamber setups have been primarily used for studying the biophysical properties of pore forming proteins. Within the last 10 years, instruments for automated lipid bilayer measurements have been developed and are now commercially available. This chapter focuses on protein purification and reconstitution of channel-forming proteins into lipid bilayers using a classic setup and on the commercially available systems, the Orbit mini and Orbit 16.

Multielectrode Arrays.

Multielectrode arrays (MEAs) are grids of substrate-integrated microelectrodes that allow for electrophysiological interrogation of dissociated cell cultures or tissue slices. Here we discuss the use of nonimplantable electrodes for studies. The methods described attempt to provide a starting point for researchers new to the field who wish to begin to utilize this powerful, but daunting technology and quickly apply the basic principles to their own research interests.

A DNA-based voltmeter for organelles.

The role of membrane potential in most intracellular organelles remains unexplored because of the lack of suitable tools. Here, we describe Voltair, a fluorescent DNA nanodevice that reports the absolute membrane potential and can be targeted to organelles in live cells. Voltair consists of a voltage-sensitive fluorophore and a reference fluorophore for ratiometry, and acts as an endocytic tracer. Using Voltair, we could measure the membrane potential of different organelles in situ in live cells. Voltair can potentially guide the rational design of biocompatible electronics and enhance our understanding of how membrane potential regulates organelle biology.

Spatially expandable fiber-based probes as a multifunctional deep brain interface.

Understanding the cytoarchitecture and wiring of the brain requires improved methods to record and stimulate large groups of neurons with cellular specificity. This requires miniaturized neural interfaces that integrate into brain tissue without altering its properties. Existing neural interface technologies have been shown to provide high-resolution electrophysiological recording with high signal-to-noise ratio. However, with single implantation, the physical properties of these devices limit their access to one, small brain region. To overcome this limitation, we developed a platform that provides three-dimensional coverage of brain tissue through multisite multifunctional fiber-based neural probes guided in a helical scaffold. Chronic recordings from the spatially expandable fiber probes demonstrate the ability of these fiber probes capturing brain activities with a single-unit resolution for long observation times. Furthermore, using Thy1-ChR2-YFP mice we demonstrate the application of our probes in simultaneous recording and optical/chemical modulation of brain activities across distant regions. Similarly, varying electrographic brain activities from different brain regions were detected by our customizable probes in a mouse model of epilepsy, suggesting the potential of using these probes for the investigation of brain disorders such as epilepsy. Ultimately, this technique enables three-dimensional manipulation and mapping of brain activities across distant regions in the deep brain with minimal tissue damage, which can bring new insights for deciphering complex brain functions and dynamics in the near future.

[Recommendations on neurophysiological studies during the COVID-19 pandemic]. / Recomendaciones sobre estudios neurofisiológicos en tiempos de pandemia de COVID-19.

At the end of January, the current outbreak of COVID-19 coronavirus disease was declared an important international public health emergency. In Spain, since the government declared the state of alarm on 14 March 2020, doctors responsible for carrying out neurophysiological tests have been performing them without any consensus criterion or clear safety guidelines for doctors, technicians or patients. The following recommendations, based on current knowledge of the disease and therefore liable to change in the future, are proposed when the pandemic appears to have entered a process of decreasing virulence and, with it, the strict containment measures established to date. However, in view of the possibility of a second wave of the pandemic, it seems necessary to establish basic and minimum recommendations to respect the patient's right to appropriate care, similar to that provided prior to the pandemic, and to maintain minimum safety standards for the patients themselves and for the doctors, technicians and health personnel carrying out these tests. These recommendations concern the constitution of a priority based on the reason for consultation, the establishment of calls to check the patient's clinical situation before going to the outpatient department and the rules for carrying out neurophysiological tests, which are generally based on the preservation of hospital circuits, respect for and observation of the known barriers to contagion of this disease, and the use of disposable material. These recommendations are of particular interest, especially given the uncertainty of not knowing the evolution of the SARS-CoV-2 infection in the coming weeks or months.

TITLE: Recomendaciones sobre estudios neurofisiológicos en tiempos de pandemia de COVID-19.A finales de enero, la Organización Mundial de la Salud declaró el brote actual de la enfermedad por coronavirus COVID-19 como emergencia de salud pública de importancia internacional. En España, desde que el 14 de marzo de 2020 el Gobierno decretase el estado de alarma, los médicos encargados de las pruebas neurofisiológicas las hemos estado realizando sin tener un criterio consensuado ni unas pautas adecuadas de seguridad claras para los facultativos, los técnicos ni los pacientes. Las siguientes recomendaciones, basadas en el actual conocimiento de la enfermedad y, por tanto, susceptibles de variaciones en el futuro, se proponen cuando la pandemia parece que ha entrado en un proceso de disminución de la virulencia y, con ello, las medidas estrictas de confinamiento hasta ahora mantenidas; sin embargo, ante la posibilidad de una segunda oleada de rebrotes de la pandemia, parece necesario establecer unas recomendaciones básicas y de mínimos para respetar el derecho del paciente a una atención adecuada, similar a la previa a la pandemia, y mantener unos mínimos de seguridad para los propios pacientes y los médicos, técnicos y personal sanitario que realizan estas pruebas. Se trata de recomendaciones sobre el establecimiento de una prioridad basándose en el motivo de consulta, el establecimiento de llamadas de comprobación de la situación clínica del paciente antes de acudir a la consulta externa y las normas de ejecución de las pruebas neurofisiológicas, que se basan, en general, en la preservación de circuitos hospitalarios, el respeto y el cuidado de las barreras de contagio conocidas de esta enfermedad, y la utilización de material desechable. Estas recomendaciones son de especial interés, sobre todo por la incertidumbre de no saber la evolución de la infección por el SARS-CoV-2 en las próximas semanas o meses.

An approach for long-term, multi-probe Neuropixels recordings in unrestrained rats.

The use of Neuropixels probes for chronic neural recordings is in its infancy and initial studies leave questions about long-term stability and probe reusability unaddressed. Here, we demonstrate a new approach for chronic Neuropixels recordings over a period of months in freely moving rats. Our approach allows multiple probes per rat and multiple cycles of probe reuse. We found that hundreds of units could be recorded for multiple months, but that yields depended systematically on anatomical position. Explanted probes displayed a small increase in noise compared to unimplanted probes, but this was insufficient to impair future single-unit recordings. We conclude that cost-effective, multi-region, and multi-probe Neuropixels recordings can be carried out with high yields over multiple months in rats or other similarly sized animals. Our methods and observations may facilitate the standardization of chronic recording from Neuropixels probes in freely moving animals.

OSERR: an open-source standalone electrophysiology recording system for rodents.

Behavioral assessment of rodents is critical for investigation of brain function in health and disease. In vivo neurophysiological recordings are powerful tools to mechanistically dissect neural pathways that underlie behavioral changes, and serve as markers for dynamics, efficacy and safety of potential therapeutic approaches. However, most in vivo recording systems require tethers or telemetry receivers, limiting their compatibility with some behavioral tests. Here, we developed an open-source standalone electrophysiology recording system for rodents (OSERR). It is a tether-free, standalone recording device with two channels, a reference and a ground, that acquires, amplifies, filters and stores data all in itself. Thus, it does not require any cable or receiver. It is also compact and light-weight, and compatible with juvenile mice, as well as multiple recording modalities and standard electrode implantation methods. In addition, we provide the complete design of hardware, and software for operation. As an example, we demonstrated that this standalone system, when configured with a bandwidth of 1-120 Hz and gain of 1000, successfully collected EEG signals during induced seizure, extended recording, anesthesia, and social interactions in mice. The design of this system is practical, economical, and freely available. Thus, this system could enable recording of brain activity during diverse behavioral assays in a variety of arenas and settings, and allow simultaneous recordings from multiple subjects to examine social behaviors. Importantly, with the open-source documentation, researchers could customize the design of the system to their specific needs.

Intracellular neuronal recording in awake nonhuman primates.

Intracellular neuronal recordings from the brain of awake nonhuman primates have remained difficult to obtain because of several formidable technical challenges, such as poor recording stability and difficulties in maintaining long-term recording conditions. We have developed a technique to record neuronal activity by using a coaxial guide tube and sharp electrode assembly, which allows researchers to repeatedly and reliably perform intracellular recordings in the cortex of awake marmosets. Recordings from individual neurons last from several minutes to more than an hour. A key advantage of this approach is that it does not require dura removal, permitting recordings over weeks and months in a single animal. This protocol describes the step-by-step procedures for construction of a custom-made marmoset chair, head-cap implantation, preparation of the sharp electrode and guide tube, neuronal recording and data analysis. As the technique is practical and easy to adapt, we anticipate that it can also be applied to other mammalian models, including larger-size nonhuman primates.