Recording whole-brain activity with single neuron resolution and millisecond timescale precision is crucial tounderstanding how individual cells and complex neural circuits interact in both time and space. Simultaneousrecording and stimulation of large populations of neurons distributed throughout the brain are needed torigorously evaluate theories of neural computation at the cellular level in mammals, and extended longitudinalrecordings are required to establish general principles for neuronal circuits/dynamics and how complexneuronal activity relates to behavior, both to further our fundamental understanding of the brain, but also tosurface 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, anelectrophysiology recording system designed to take advantage of novel, close-packed 1000-channel siliconprobes originally developed by the Synthetic Neurobiology Group at MIT. These ultra-high-channel-countprobes allow for more neurons to be recorded simultaneously, opening up new lines of scientific inquiry, andthe dense packing of the electrodes permits spatial oversampling of the neurons, allowing for automated spikesorting 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 aprobe/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 Catkinprobe/headstage combo is tethered to the Willow DAQ system by an ultra thin and lightweight cable (a singleshielded 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 mayresult in altered behavior from animals. To address these needs, this application proposes the development ofa first-of-its-kind fully untethered 1000-channel-simultaneous 30kHz in-vivo electrophysiologicalrecording module, to be made available as a lightweight add-on to the extant Willow system.
Public Health Relevance Statement: PROJECT NARRATIVE
Electrophysiological recording systems allow direct observation of neural activity in animal subjects. This
facilitates the study of crucial neuroscientific topics such as development, learning and memory, and cognition,
as well as brain diseases such as Alzheimer's, epilepsy, Parkinson's, and depression. LeafLabs' tools for
performing high-channel count electrophysiology experiments in freely-moving rodents will allow researchers to
collect and interpret neural data at a large scale, with few experimental constraints to environment complexity
or the types of naturalistic behaviors studied.
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