In tetrode recordings, the cell types of the recorded units are difficult to determine based on electrophysiological characteristics alone. Optotagging, the use of optogenetic stimulation at the tip of electrodes to elicit spikes from genetically identified cells, is a method to overcome this challenge. However, recording from many different cells requires advancing electrodes and light sources slowly through the brain with a microdrive. Existing designs suffer from a number of drawbacks, such as limited stability and precision, high cost, complex assembly, or excessive size and weight. We designed TetrODrive as a microdrive that can be 3D printed on an inexpensive desktop resin printer and has minimal parts, assembly time, and cost. The microdrive can be assembled in 15 minutes and the price for all materials, including the 3D printer, is lower than a single commercial microdrive. To maximize recording stability, we mechanically decoupled the drive mechanism from the electrical and optical connectors. The developed microdrive is small and light enough to be carried effortlessly by a mouse. It provides high signal-to-noise ratio recordings from optotagged units, even across recording sessions. Owing to its moveable optical fiber, our microdrive can also be used for fiber photometry. We evaluated our microdrive by recording single units and calcium signals in the ventral tegmental area (VTA) of mice and confirmed cell identity via optotagging. Thereby we found units not following the classical reward prediction error model. TetrODrive is a tiny, lightweight, and affordable microdrive for optophysiology in mice. Its open design, price, and built-in characteristics can significantly expand the use of microdrives in mice.
bioRxiv Subject Collection: Neuroscience