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A microprobe for parallel optical and electrical recordings from single neurons in vivo

Abstract

Recording electrical activity from identified neurons in intact tissue is key to understanding their role in information processing. Recent fluorescence labeling techniques have opened new possibilities to combine electrophysiological recording with optical detection of individual neurons deep in brain tissue. For this purpose we developed dual-core fiberoptics–based microprobes, with an optical core to locally excite and collect fluorescence, and an electrolyte-filled hollow core for extracellular single unit electrophysiology. This design provides microprobes with tips <10 μm, enabling analyses with single-cell optical resolution. We demonstrate combined electrical and optical detection of single fluorescent neurons in rats and mice. We combined electrical recordings and optical Ca2+ measurements from single thalamic relay neurons in rats, and achieved detection and activation of single channelrhodopsin-expressing neurons in Thy1::ChR2-YFP transgenic mice. The microprobe expands possibilities for in vivo electrophysiological recording, providing parallel access to single-cell optical monitoring and control.

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Figure 1: The microprobe.
Figure 2: Microprobe optical resolution.
Figure 3: Single-unit recordings from neurons in vivo.
Figure 4: Optical and electrical signal profiles of single cells in vivo.
Figure 5: Monitoring Ca2+ fluctuations confirm optical and electrical recording from the same neuron in vivo.
Figure 6: Detection and activation of single ChR2-expressing neurons in vivo.

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Acknowledgements

This work was supported by the Canadian Institutes for Health Research. Y.D.K. was funded by a Chercheur National award from the Fonds de la recherche en santé du Québec. Y.L. and S.D. received a Studentship from the Canadian Institutes for Health Research Neurophysics Training program grant. We thank A. Proulx and A. Croteau for the collaboration on the dual-core fiber design and fabrication; D. Côté and A. Castonguay for helpful comments on the manuscript; and S.L. Côté, K. Bachand, K. Vandal and M. Demers for expert technical assistance.

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Y.L., R.V. and Y.D.K. designed the microprobe. Y.L., S.D., G.L., C.B., M.D. and Y.D.K. designed the experiments. Y.L., S.D., G.L. and Y.D.K. analyzed data. Y.L., S.D., G.L. and C.B. performed experiments. S.D. performed Ca2+ measurement and photostimulation experiments. Y.L. and S.D. performed numerical simulations. Y.L., S.D., G.L., C.B., M.D., R.V. and Y.D.K. contributed to writing the manuscript.

Corresponding author

Correspondence to Yves De Koninck.

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The authors declare no competing financial interests.

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Supplementary Figures 1–4 and Supplementary Data (PDF 1592 kb)

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LeChasseur, Y., Dufour, S., Lavertu, G. et al. A microprobe for parallel optical and electrical recordings from single neurons in vivo. Nat Methods 8, 319–325 (2011). https://doi.org/10.1038/nmeth.1572

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