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Closed-loop optogenetic intervention in mice

Nature Protocols volume 8, pages 1475–1493 (2013)Cite this article

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Abstract

Optogenetic interventions offer novel ways of probing, in a temporally specific manner, the roles of specific cell types in neuronal network functions of awake, behaving animals. Despite the unique potential for temporally specific optogenetic intervention in disease states, a major hurdle in its broad application to unpredictable brain states in a laboratory setting is constructing a real-time responsive system. We recently created a closed-loop system for stopping spontaneous seizures in chronically epileptic mice by using optogenetic intervention. This system performs with a very high sensitivity and specificity, and the strategy is not only relevant to epilepsy but also can also be used to react to diverse brain states in real time, with optogenetic or other interventions. The protocol presented here is highly modular and requires variable amounts of time to perform. We describe the basic construction of a complete system, and we include our downloadable custom closed-loop detection software, which can be used for this purpose.

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Figure 1: Generating implantable optical fibers.
Figure 2: Assembling optrodes for implantation.
Figure 3: Implanting the optical fiber and electrode headstage.
Figure 4: Equipment setup.
Figure 5: Summary of detection algorithms.
Figure 6: On-line seizure detection and fiber tract location.

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Acknowledgements

We thank S. Olsen, H. Adesnik and M. Scanziani for sharing expertise in putting together components of an LED stimulation setup, and we thank J. Echegoyen for sharing his expertise in performing tethered EEG recordings. This work was supported by a US National Institutes of Health grant NS074702 (to I.S.), by the Epilepsy Foundation (to C.A.) and by the George E. Hewitt Foundation for Medical Research (to E.K.-M.).

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Author notes

  1. Caren Armstrong and Esther Krook-Magnuson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy & Neurobiology, University of California, Irvine, School of Medicine, Irvine, California, USA

    Caren Armstrong, Esther Krook-Magnuson, Mikko Oijala & Ivan Soltesz

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  1. Caren Armstrong
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Contributions

M.O. designed the custom MATLAB software, E.K.-M. and C.A. contributed equally and performed the experiments and C.A., E.K.-M., M.O. and I.S. designed the experiments and prepared the manuscript.

Corresponding author

Correspondence to Caren Armstrong.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Data

On-line seizure detection and analysis software. (a) MCRInstaller (2011b).exe. The MATLAB runtime environment (2011b) which is necessary to run the custom software. This file should be run only once on every computer that will be using the custom MATLAB software prior to attempting to open them. (b) Soltesz_Recorder_v1.exe. A modified version of the custom MATLAB recording software used to achieve online seizure detection in Krook-Magnuson et al 2013 (Soltesz_Recorder_v1.exe), (c) Soltesz_Analyzer_v1.exe. A modified version of the custom MATLAB software for analyzing recorded files. (d) sample data.mat. A short segment of recorded data which can be opened and examined using the Analysis Software (Supplementary Data 1c) for users wishing to gain practice with tuning a sample data set. (e) readme.txt. This allows the user to quickly get started installing and using the software files. (ZIP 426275 kb)

Supplementary Manual

On-line seizure detection and analysis software user guide. Also contained in the zipped Supplementary Data 1 file for reference, the User Guide contains information on each of the different functions available in the recorder and analyzer programs, as well as more detailed information about the calculations used for each parameter. Portions of this manual were modified from the Supplementary Material of Krook-Magnuson et al.2. (PDF 1975 kb)

Supplementary Table 1

Equipment and reagents. This file contains the ordering information for the equipment and supplies utilized in the protocol and in Krook-Magnuson et al.2. (PDF 2849 kb)

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Armstrong, C., Krook-Magnuson, E., Oijala, M. et al. Closed-loop optogenetic intervention in mice. Nat Protoc 8, 1475–1493 (2013). https://doi.org/10.1038/nprot.2013.080

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