PROJECT SUMMARY Within every brain region, neurons can be classified into dozens or hundreds of different cell types, each with unique functional roles and unique impacts on disease states. Traditionally, in vivo electrophysiological recordings—which have made invaluable contributions to our understanding of the neural basis of behavior— have not been able to distinguish the activity of genetically defined cell types. Despite recent advances in our ability to measure action potentials from many neurons simultaneously, it remains difficult to connect these spike trains to underlying cell types and all that is known about their morphology, connectivity patterns, and intrinsic properties. Here, we propose to extend the widely used Neuropixels platform by creating a version of these probes that is capable of both high-density electrophysiological recording and multi-color light delivery. This device, called Neuropixels Opto, could be used to identify cell types through an approach known as “optotagging,” while also facilitating precise manipulations of genetically defined neural populations. We will work with IMEC, a nanoelectronics R&D organization with exclusive access to world-class fabrication facilities, to design and build a fully integrated implantable recording device with 1280 electrical readout sites, up to 48 red light emitters, and up to 62 blue light emitters. A proof-of-concept version of this probe has already been delivered to the Allen Institute, where it was successfully used in an optotagging experiment. However, more work is required to develop a device that can be manufactured at scale and sold for around $2500/probe, in order to facilitate its dissemination throughout the systems neuroscience community. In collaboration with three external test sites, we will validate the efficacy of Neuropixels Opto for performing cell-type-specific recordings and manipulations in four brain regions: the visual cortex, entorhinal cortex, striatum, and the ventral tegmental area. In addition, we will extend popular data acquisition packages by developing modules for controlling these probes, as well as create new transgenic mouse lines that make it much simpler for users to carry out dual-color optogenetic manipulations. Taken together, these efforts will make Neuropixels Opto a powerful, accessible, and indispensable tool for understanding the role that different cell types play in living brains.

PROJECT NARRATIVE Neurons in the human brain can be categorized into thousands of distinct “cell types,” each with unique properties, functions, and contributions to disease states. A comprehensive understanding of different cell types requires observing their electrical activity in living brains—however, the current technologies for doing this are quite limiting. We propose to develop a new device that makes it much easier for researchers to record from, identify, and stimulate different cell types throughout the brain, and which is also compact and affordable.