Optetrode: a multichannel readout for optogenetic control in freely moving mice

Abstract

Recent advances in optogenetics have improved the precision with which defined circuit elements can be controlled optically in freely moving mammals; in particular, recombinase-dependent opsin viruses, used with a growing pool of transgenic mice expressing recombinases, allow manipulation of specific cell types. However, although optogenetic control has allowed neural circuits to be manipulated in increasingly powerful ways, combining optogenetic stimulation with simultaneous multichannel electrophysiological readout of isolated units in freely moving mice remains a challenge. We designed and validated the optetrode, a device that allows for colocalized multi-tetrode electrophysiological recording and optical stimulation in freely moving mice. Optetrode manufacture employs a unique optical fiber-centric coaxial design approach that yields a lightweight (2 g), compact and robust device that is suitable for behaving mice. This low-cost device is easy to construct (2.5 h to build without specialized equipment). We found that the drive design produced stable high-quality recordings and continued to do so for at least 6 weeks following implantation. We validated the optetrode by quantifying, for the first time, the response of cells in the medial prefrontal cortex to local optical excitation and inhibition, probing multiple different genetically defined classes of cells in the mouse during open field exploration.

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Figure 1: Optetrode design.
Figure 2: Optetrode-facilitated electrophysiology during broad optogenetic stimulation during the OFT.
Figure 3: Optetrode-facilitated electrophysiology during cell type–specific optogenetic stimulation in the context of the OFT.
Figure 4: Behavioral and neural activity effects of optogenetic stimulation during the OFT.
Figure 5: Optetrode projection targeting: driving axonal inputs from BLA into mPFC.

Change history

  • 11 December 2011

    In the version of this article initially published online, the middle initial of author Lisa A. Gunaydin was missing. The error has been corrected for the print, PDF and HTML versions of this article.

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Acknowledgements

We thank S. Arber for the PV::Cre transgenic mouse line. P.A. thanks D.G. Walker for advice on mechanical design. P.A. was supported by a Dean's fellowship from Stanford University School of Medicine, I.W. was supported by the Helen Hay Whitney Foundation, I.G. was supported by a Machiah fellowship and the Weizmann Institute Women in Science award, L.G. was supported by a National Science Foundation Integrative Graduate Education and Research Traineeship Award, and L.A.G. was supported by a BioX fellowship from Stanford University. L.M.F. and K.D. received support from a GO grant from the National Institute of Neurological Disorders and Stroke. Full funding information for K.D. is listed at http://www.stanford.edu/group/dlab/optogenetics/funding/ and includes the Gatsby Charitable Foundation, the Defense Advanced Research Projects Agency Reorganization and Plasticity to Accelerate Injury Recovery Program, the California Institute for Regenerative Medicine, the McKnight Foundation, the National Institute of Mental Health, and the National Institute on Drug Abuse.

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P.A., A.S.A. and K.D. designed the experiments and analyzed the data. P.A. devised and designed the device. P.A. and A.S.A. collected and analyzed electrophysiological and behavioral data. P.A., A.S.A. and I.G. performed immunohistochemical processing and confocal imaging. M.W. and I.W. aided in the development of the device and surgical procedure. M.W. and L.M.F. aided with neuronal sorting procedures. L.G. aided in statistical analysis. L.A.G. contributed data regarding defined-projection manipulation. L.M.F. aided the analysis of the electrophysiological data. K.D. supervised all aspects of the work. P.A., A.S.A. and K.D. wrote the paper.

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Correspondence to Karl Deisseroth.

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Anikeeva, P., Andalman, A., Witten, I. et al. Optetrode: a multichannel readout for optogenetic control in freely moving mice. Nat Neurosci 15, 163–170 (2012). https://doi.org/10.1038/nn.2992

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