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Stable long-term chronic brain mapping at the single-neuron level

Nature Methods volume 13, pages 875882 (2016) | Download Citation

Abstract

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

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Acknowledgements

We thank J. Huang for help with recording instrumentation, J. Liu and J. Tian for training in chronic surgery, S. Patel for help with data analysis and stimulation implementation, G. Guitchounts and S. Wolff for help in freely behaving mouse recording implementation and data interpretation, and C. Perez Estrada for helpful discussions. C.M.L. acknowledges support from the Air Force Office of Scientific Research, the Star Family and Fidelity Biosciences Funds, and the Harvard University Physical Sciences and Engineering Accelerator award. This work was performed in part at the Harvard University Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation.

Author information

Author notes

    • Tian-Ming Fu
    • , Guosong Hong
    •  & Tao Zhou

    These authors contributed equally to this work.

Affiliations

  1. Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA.

    • Tian-Ming Fu
    • , Guosong Hong
    • , Tao Zhou
    •  & Charles M Lieber
  2. John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA.

    • Thomas G Schuhmann
    • , Robert D Viveros
    •  & Charles M Lieber

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Contributions

T.-M.F., G.H. and C.M.L. designed the experiments. T.-M.F., G.H., T.Z., T.G.S. and R.D.V. performed the experiments. T.-M.F., G.H., T.Z. and C.M.L. analyzed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Charles M Lieber.

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    Supplementary Text and Figures

    Supplementary Figures 1–14 and Supplementary Tables 1–3

Videos

  1. 1.

    Chronic recordings from a freely behaving mouse with implanted mesh electronics probe.

    This video shows a mouse with a head-mounted voltage-amplifier roaming freely in a cage with randomly positioned food pellets during recording. The frame rate is 25 frames per second (fps) and the video is played at 1× real time. The mesh electronics was injected into the somatosensory cortex and hippocampus, and bonded to the interface cable as described in the Online Methods.

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DOI

https://doi.org/10.1038/nmeth.3969

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