Untethered high channel count electrophysiology for freely-moving animals - PROJECT SUMMARY Recording whole-brain activity with single neuron resolution and millisecond timescale precision is crucial to understanding how individual cells and complex neural circuits interact in both time and space. Simultaneous recording and stimulation of large populations of neurons distributed throughout the brain are needed to rigorously evaluate theories of neural computation at the cellular level in mammals, and extended longitudinal recordings are required to establish general principles for neuronal circuits/dynamics and how complex neuronal activity relates to behavior, both to further our fundamental understanding of the brain, but also to surface underlying causes of neurological and psychiatric conditions such as Alzheimer’s, Parkinson’s, TBI, epilepsy, and depression, and to aid development of novel and more effective treatments. These are key goals of the BRAIN initiative, and the driving force behind LeafLabs' Willow, an electrophysiology recording system designed to take advantage of novel, close-packed 1000-channel silicon probes originally developed by the Synthetic Neurobiology Group at MIT. These ultra-high-channel-count probes allow for more neurons to be recorded simultaneously, opening up new lines of scientific inquiry, and the dense packing of the electrodes permits spatial oversampling of the neurons, allowing for automated spike sorting techniques with greatly increased capability for tracking individual units. Additionally, LeafLabs' Catkin, a custom 1000 channel neurosensing IC chip (filter, amplification, multiplexing, and analog-digital conversion) has been developed to integrate with these probes, resulting in a probe/headstage combo suitable for use in freely-moving electrophysiology experiments that reduces size, weight, and cost each by a factor of 10 compared to commercially available headstages. Currently, the Catkin probe/headstage combo is tethered to the Willow DAQ system by an ultra thin and lightweight cable (a single shielded 32 AWG twisted pair), resulting in a system ideal for many prolonged freely moving experiments. However, in certain behavioral setups, even a lightweight, minimalist cable is undesirable. For example, because the high data rates are incompatible with approaches used to manage the cable tether (commutators), researchers must occasionally intervene to de-tangle cables; or, the presence of a tether may result in altered behavior from animals. To address these needs, this application proposes the development of a first-of-its-kind fully untethered 1000-channel-simultaneous 30kHz in-vivo electrophysiological recording module, to be made available as a lightweight add-on to the extant Willow system.