Abstract
Brain function depends on simultaneous electrical, chemical and mechanical signaling at the cellular level. This multiplicity has confounded efforts to simultaneously measure or modulate these diverse signals in vivo. Here we present fiber probes that allow for simultaneous optical stimulation, neural recording and drug delivery in behaving mice with high resolution. These fibers are fabricated from polymers by means of a thermal drawing process that allows for the integration of multiple materials and interrogation modalities into neural probes. Mechanical, electrical, optical and microfluidic measurements revealed high flexibility and functionality of the probes under bending deformation. Long-term in vivo recordings, optogenetic stimulation, drug perturbation and analysis of tissue response confirmed that our probes can form stable brain-machine interfaces for at least 2 months. We expect that our multifunctional fibers will permit more detailed manipulation and analysis of neural circuits deep in the brain of behaving animals than achievable before.
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Acknowledgements
This work was supported in part by the National Science Foundation under a CAREER award to P.A. (CBET–1253890), the Center for Materials Science and Engineering (DMR-0819762), the Center for Sensorimotor Neural Engineering (EEC-1028725), the McGovern Institute for Brain Research, the US Army Research Laboratory and the US Army Research Office through the Institute for Soldier Nanotechnologies under contract number W911NF-13-D-0001, and a grant from the Simons Foundation to the Simons Center for the Social Brain at MIT. The authors are grateful to G. Feng for the generous donation of Thy1-ChR2-YFP mice, W. Jia and J. LaVine for initial help with microfluidic characterization and C. Moritz and L.H. Tsai for assistance with equipment.
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P.A., Y.F. and U.P.F. designed the study. X.J. and A.C. drew multifunctional and multielectrode fibers, respectively. X.J. and J.S. connectorized multimodality probes. A.C. and C.M.T. connectorized and characterized multielectrode probes. C.L., L.W., X.J., C.H. and J.S. evaluated optical properties. A.C., C.M.T. and X.J. obtained electrode impedance spectra. A.C. conducted mechanical tests. X.J. and U.P.F. performed microfluidic characterization. U.P.F., A.C., X.J. and P.A. performed in vivo experiments. R.A.K., U.P.F., A.C., J.S. and C.M.T. investigated tissue response. U.P.F., A.C., R.A.K., X.J., Y.F. and P.A. analyzed the data and wrote the manuscript.
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Canales, A., Jia, X., Froriep, U. et al. Multifunctional fibers for simultaneous optical, electrical and chemical interrogation of neural circuits in vivo. Nat Biotechnol 33, 277–284 (2015). https://doi.org/10.1038/nbt.3093
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DOI: https://doi.org/10.1038/nbt.3093
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