The common marmoset (Callithrix jacchus) has quickly grown in popularity as a model to study brain function in recent years. This growing popularity is due to the accessibility of the marmoset's smooth cortex, the similarities in neural functional organization with humans and other primates, and the small size and fast breeding rate¹. As this model organism has grown in popularity, there has been rapid development in the neurophysiological techniques suited for use in the marmoset brain. Electrophysiology methods are widely used in neuroscience to study the activity of single neurons in the cortex of both rodents and primates, resulting in unparalleled temporal resolution and location access. Due to the relative novelty of the marmoset monkey as a model of visual neuroscience, the optimization of awake-behaving electrophysiology techniques is still evolving. Previous studies have shown the establishment of robust protocols for electrophysiology in anesthetized preparations², and early awake-behaving neurophysiology studies have shown the reliability of single-channel tungsten electodes³. In recent years, researchers have established the use of silicon-based microelectrode arrays for awake-behaving neurophysiology⁴. However, the marmoset poses unique targeting challenges due to its small brain size and lack of anatomical landmarks. This protocol outlines how to construct and use a micro-drive recording system suitable for the marmoset that allows for the recording of large populations of neurons with silicon linear arrays while producing minimal tissue damage.

Working with the marmoset poses a challenge due to the smaller scale of the retinotopic maps in the visual cortex as compared to larger primates. A slight shift of the electrodes by just 1 mm can result in significant changes in the maps. Moreover, researchers often need to alter the placement of the electrodes between the recording sessions to obtain a broader range of retinotopic positions in the visual cortex. Current semi-chronic preparations do not allow for the adjustment of the electrode positioning daily or with enough precision to target specific locations at sub-millimeter scales⁵. With this in mind, the proposed micro-drive system utilizes an X-Y electrode stage that mounts a lightweight micro-drive to a recording chamber and allows for the sub-millimeter targeting of cortical sites. The moveable X-Y stage components allow for vertical and horizontal movement of the linear array in order to traverse the cortical areas systematically, which is required to identify areas of interest (via retinotopy and tuning properties). Across recording sessions, researchers can also manually adjust the X-Y stage to shift the targeted sites within the area. This is a key advantage over alternative techniques using semi-chronic recording preparations, which do not have easy electrode targeting mechanisms.

The micro-drive is a versatile tool that enables the attachment of various silicon arrays to be mounted for lowering into the cortex. In this protocol, a custom probe with two 32-channel linear arrays spaced 200 µm apart was used for the investigation of laminar circuits spanning the cortical depth. Most methods for probing the neural circuitry typically sample the electrical potentials or single units averaged across all the layers of the cerebral cortex. However, recent research has revealed intriguing findings about cortical laminar microcircuits⁶. By utilizing the micro-drive, researchers can use laminar probes and make fine adjustments to the recording depth to ensure comprehensive sampling across all the layers.

This system can be constructed with commercially available components and is easily modified for different experimental techniques or probes. The key advantages of this preparation are the ability to change the X-Y recording position with sub-millimeter precision and to control the depth of the recording within the cortex. This protocol presents step-by-step instructions for constructing the X-Y stage micro-drive and neurophysiology recording techniques.