Although great strides have been made in characterizing the properties of single neurons, enormous challenges remain before we understand how billions of neurons work in concert to produce complex phenomena such as perception, learning, and memory. Far and away, the biggest obstacle towards progress in systems neuroscience has been the difficulty of observing the activity of large populations of neurons in freely behaving animals. The flow of electricity in the form of action potentials and synaptic currents is the currency of the brain, and neural activity and synaptic changes are sensitive to millisecond timescales. Hence electrophysiology has been the gold standard for monitoring the brain since it directly measures electrical activity with sub-millisecond resolution. However, state of the art multi-electrode arrays have about 100 recording sites and can thus sample neuronal activity only very sparsely. This constraint makes it difficult to infer anything about global brain patterns and their evolution in time. To overcome these limitations, we propose to develop nanoprobe arrays which preserve the exceptional temporal resolution of electrophysiology while drastically increasing its spatial resolution and scale. The proposed arrays will have tens of thousands of recording sites-two orders of magnitude higher than current devices-and will enable mapping brain activity across entire volumes of brain tissue with unprecedented spatiotemporal resolution, exposing fundamental regularities far beyond the reach of current technologies. This development will fuel innovations at many levels: the design and nanofabrication of probes, integration with active electronics, development of high-speed acquisition systems, implantable interfaces for extensive testing in behaving animals, and development of computational and analysis infrastructure. Our goal is to go beyond proof of concept prototypes towards widely available transformative research tools by employing foundr

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1MH099907-03
Application #
8541058
Study Section
Special Emphasis Panel (ZGM1-NDPA-A (01))
Program Officer
Freund, Michelle
Project Start
2011-09-30
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$795,400
Indirect Cost
$310,400
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
009584210
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Shan, Kevin Q; Lubenov, Evgueniy V; Siapas, Athanassios G (2017) Model-based spike sorting with a mixture of drifting t-distributions. J Neurosci Methods 288:82-98
Hulse, Brad K; Lubenov, Evgueniy V; Siapas, Athanassios G (2017) Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice. Cell Rep 18:136-147
Rios, Gustavo; Lubenov, Evgueniy V; Chi, Derrick et al. (2016) Nanofabricated Neural Probes for Dense 3-D Recordings of Brain Activity. Nano Lett 16:6857-6862
Shan, Kevin Q; Lubenov, Evgueniy V; Papadopoulou, Maria et al. (2016) Spatial tuning and brain state account for dorsal hippocampal CA1 activity in a non-spatial learning task. Elife 5:
Hulse, Brad K; Moreaux, Laurent C; Lubenov, Evgueniy V et al. (2016) Membrane Potential Dynamics of CA1 Pyramidal Neurons during Hippocampal Ripples in Awake Mice. Neuron 89:800-13
Sauerbrei, Britton A; Lubenov, Evgueniy V; Siapas, Athanassios G (2015) Structured Variability in Purkinje Cell Activity during Locomotion. Neuron 87:840-52