Truly large scale electrophysiology--simultaneous recording of thousands of individual neurons in multiple brain areas--remains an elusive goal of systems neuroscience. The traditional approach of studying single neurons in isolation assumes that the brain can be understood one component at a time. However, in order to fully understand the function of whole brain circuits it is essential to observe the interactions of large numbers of neurons in multiple brain areas simultaneously. Microelectromechanical systems (MEMS) based electrode arrays are increasingly being used to address this challenge. However, in order for these arrays to provide a transformative advance in this field, it is imperative to scale up the number of electrodes by at least order of magnitude, and at the same time scale down the instrumentation to make the technology usable in freely behaving animals.
This project will establish a complete system for multi-scale electrophysiology in awake, freely behaving mice, using state-of-the-art polymer and silicon nanomanufacturing to fabricate arrays of tiny, ultra-compliant implantable neural interfaces, dubbed nanoprobes. The supporting instrumentation will use a unique modular architecture with flexible microcables to allow individual positioning of multiple probes. With this system, up to 640 electrodes can be distributed in up to ten different brain regions. The stackable recording modules will be built around a commercially available application specific integrated circuit (ASIC) that has been custom designed for electrophysiological recordings, combining signal amplification, filtering, signal multiplexing, and digital sampling on a single chip. Each ASIC supports 64 channels, dramatically reducing the size, weight, and cost of the recording system. Multiplexing reduces the number of wires in the animal tether cable to just 6 wires, instead of 640. A wireless module will support up to 128 channels.
The diminutive size of the proposed instrument will revolutionize studies of the neuronal correlates of behavior, especially in small animals such as mice, and the wireless module will create new opportunities for "free roaming" large scale electrophysiology in ethologically relevant natural environments. The instrument is intended to complement recent advances in transgenic mouse models, such as light-activatable ion channels, by dramatically scaling up the number of feasible electrode implants in this increasingly important animal model. The instrument is also designed to be used with multi-wire electrodes, tetrodes, and EEG or ECoG arrays. All components of the system are mass-produced, ensuring that the instrument will be accessible to the wider neuroscience research community. Beyond basic research, results from this project will further the development of next-generation neural prosthetic devices.
