Abstract
We propose a new paradigm for dense functional imaging of brain activity to surmount the limitations of present methodologies. We term this approach “integrated neurophotonics”; it combines recent advances in microchip-based integrated photonic and electronic circuitry with those from optogenetics. This approach has the potential to enable lens-less functional imaging from within the brain itself to achieve dense, large-scale stimulation and recording of brain activity with cellular resolution at arbitrary depths. We perform a computational study of several prototype 3D architectures for implantable probe-array modules that are designed to provide fast and dense single-cell resolution (e.g., within a 1-mm3 volume of mouse cortex comprising ∼100,000 neurons). We describe progress toward realizing integrated neurophotonic imaging modules, which can be produced en masse with current semiconductor foundry protocols for chip manufacturing. Implantation of multiple modules can cover extended brain regions. Moreaux et al. describe a new paradigm for dense functional imaging of brain activity that surmounts limitations of present methodologies. It enables functional imaging from within the brain, permitting dense, large-scale brain circuit interrogation with cellular resolution at arbitrary depths.
Original language | English (US) |
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Pages (from-to) | 66-92 |
Number of pages | 27 |
Journal | Neuron |
Volume | 108 |
Issue number | 1 |
DOIs | |
State | Published - Oct 14 2020 |
Funding
M.L.R. A.S.T. and K.L.S. gratefully acknowledge funding from the NIH (grant Nos. NS090596 and NS009717), NSF (grant Nos. 1265055 and 1403817), DARPA (grant Nos. N66001-17-C-4002 and N66001-17-C-4012), IARPA (grant No. DP1EY023176), and the Kavli Foundation through Caltech's Kavli Nanoscience Institute's “Fill the gap” award program. J.K.S.P. acknowledges the Natural Sciences and Engineering Research Canada, Canadian Institutes of Health Research, and Canada Research Chair program. We thank the following individuals for their participation in various phases of this work: Joe Redford (initial numerical simulations); Eran Segev, Derrick Chi, Trevor Fowler, Xinyu Liu, Kukjoo Kim, Warren Fon (nanofabrication); Fu-Der Chen, John Straguzzi, Thomas Lordello, and Ilan Felts Almog (photonic probe characterization); and Andres Lozano, Anton Fomenko, Taufik Valiante, Homeira Moradi-Chameh, Prajay Shah, Zach Blumenfeld (in vitro and in vivo experiments). We thank François Berger, Miyoung Chun, Andrei Faraon, Leslie Greengard, Gilles Laurent, Konrad Kording, and Liam Paninski for helpful discussions. We especially thank our reviewers for their insightful comments. We are grateful for the participation of our foundry partners, including scientists and engineers at: CEA-Leti (Grenoble, France): Laurent Duraffourg, Bruno Paing, Salim Boutami, Jean-Marc Fedeli, Benoit Giffard Pierre Labeye, Hughes Metras, Eric Rouchouze, Denis Renaud, and Alexei Tchelnokov; at Advanced Micro Foundry (AMF, Singapore): Patrick Lo and Xianshu Luo; and at TSMC (Taiwan). Three patents owned by the California Institute of Technology have been pursued in connection with this work: (1) Roukes (2011). Brain-machine interface based on photonic neural probe arrays. U.S.P.T.O. Patent No. 10,638,933, Issued May 5, 2020, Priority Date: December 8, 2011. (2) Segev, E. Moreaux, L.C. Fowler, T.M. Faraon, A. Roukes, M.L. Implantable, highly collimated light-emitters for biological applications. U.S.P.T.O. Patent No. 10,471,273, Issue date: 12 November 2019; Priority date: 16 October 2015. (3) Roukes et al. (2016). One-photon integrated neurophotonic systems. U.S.P.T.O. Patent Application 20160150963, Filing date: November 5, 2014; Publication date: June 2, 2016. M.L.R., A.S.T., and K.L.S. gratefully acknowledge funding from the NIH (grant Nos. NS090596 and NS009717 ), NSF (grant Nos. 1265055 and 1403817 ), DARPA (grant Nos. N66001-17-C-4002 and N66001-17-C-4012 ), IARPA (grant No. DP1EY023176 ), and the Kavli Foundation through Caltech’s Kavli Nanoscience Institute’s “Fill the gap” award program. J.K.S.P. acknowledges the Natural Sciences and Engineering Research Canada , Canadian Institutes of Health Research , and Canada Research Chair program .
ASJC Scopus subject areas
- General Neuroscience