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SCIENCE CHINA Life Sciences, Volume 63, Issue 6: 875-885(2020) https://doi.org/10.1007/s11427-020-1675-x

An optical brain-to-brain interface supports rapid information transmission for precise locomotion control

Lihui Lu1,2,3, Ruiyu Wang3,4,5, Minmin Luo2,3,5,6,7,*
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  • ReceivedJan 16, 2020
  • AcceptedMar 5, 2020
  • PublishedMar 20, 2020

Abstract

Brain-to-brain interfaces (BtBIs) hold exciting potentials for direct communication between individual brains. However, technical challenges often limit their performance in rapid information transfer. Here, we demonstrate an optical brain-to-brain interface that transmits information regarding locomotor speed from one mouse to another and allows precise, real-time control of locomotion across animals with high information transfer rate. We found that the activity of the genetically identified neuromedin B (NMB) neurons within the nucleus incertus (NI) precisely predicts and critically controls locomotor speed. By optically recording Ca2+ signals from the NI of a “Master” mouse and converting them to patterned optogenetic stimulations of the NI of an “Avatar” mouse, the BtBI directed the Avatar mice to closely mimic the locomotion of their Masters with information transfer rate about two orders of magnitude higher than previous BtBIs. These results thus provide proof-of-concept that optical BtBIs can rapidly transmit neural information and control dynamic behaviors across individuals.


Funded by

Ministry of Science and Technology of China(2015BAI08B02)

the National Natural Science Foundation of China(91432114,91632302)

and the Beijing Municipal Government.


Acknowledgment

We thank J. Snyder for comments and language polish. M.L. is supported by Ministry of Science and Technology of China (2015BAI08B02), the National Natural Science Foundation of China (91432114 and 91632302), and the Beijing Municipal Government.


Interest statement

The author(s) declare that they have no conflict of interest. All procedures were conducted with the approval of the Animal Care and Use Committee of the National Institute of Biological Sciences, Beijing in accordance with governmental regulations of China, and conformed with the Helsinki Declaration of 1975 (as revised in 2008) concerning Animal Rights, and followed out policy concerning Informed Consent as shown on Springer.com.


Supplement

SUPPORTING INFORMATION

Figure S1 Animal pairs and flowchart of the signal transformation in the optical BtBI experiments.

Figure S2 Control experiments for optical BtBI.

Figure S3 The method of calculating information transfer rate.

Movie S1 An optical BtBI enables a Master mouse to control the locomotion of an Avatar mouse.

The supporting information is available online at http://life.scichina.com and https://link.springer.com. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


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  • Figure 1

    Neural basis of the optical brain-to-brain interface that transfers locomotor speed information. A, Schematic of fiber photometry recording of GCaMP6-expressing nucleus incertus (NI) neuromedin B (NMB) neurons. The blue color bar indicates fiber optic. AAV, adeno-associated virus; DIO, double-floxed inverted open reading frame. B, A representative coronal section showing GCaMP6m expression pattern in the NI and the site of optical fiber placement for recording Ca2+ signals. Scale bar, 200 µm. C, A fiber photometry system recorded Ca2+ transients from GCaMP6-expressing NI neurons of a NMB-Cre mouse running on a wheel treadmill. DM, dichroic mirror; PMT, photomultiplier tube; DAQ, data acquisition. D, Representative recording traces of GCaMP fluorescence change (upper) and the matched locomotor speed of a head-fixed mouse (lower). The correlation coefficient between GCaMP fluorescence change and animal locomotor speed is 0.81±0.02, mean±SEM (n=10 mice). E, Significantly higher Ca2+ signals when a mouse actively moved (Wilcoxon matched-pairs signed rank test; n=10 mice). F and G, Average Ca2+ signals (blue) and running speed (black) as a function of time relative to locomotor onset and termination. The rise of Ca2+ signals preceded the locomotor onset for about 0.9 s (0.93±0.15 s; mean±SEM) and the decay of Ca2+ signals lagged behind the termination of locomotion for about 1 s (1.02±0.13 s; n=10 mice). Red segments indicate statistically significant increase from the baseline (P<0.01; multivariate permutation test). H and I, Population data of the EmGFP-expressing control animals during acceleration (H) and deceleration (I) events (n=13 mice). J, The performance of different decoders on predicting locomotor speed from GCaMP6m signals of NI neurons. Black line, measured speed; dashed red line, linear prediction; dashed cyan line, polynomial nonlinear prediction (abbreviated as “nonlinear”); dashed blue line, artificial neural network (ANN) prediction. K, Correlation coefficient for predicted locomotor speed using linear (red), nonlinear (cyan), or ANN (blue) prediction model (non-parametric Dunn’s multiple comparisons test, n=10 mice). L–N, Average speed confusion matrix using normalized measured speed and linear prediction speed (L), nonlinear prediction speed (M), or ANN prediction speed (N). Color bar indicates confusion values that were normalized by row. O, Schematic of optogenetic activation of NI NMB neurons. The blue color bar indicates fiber optic. P, The average locomotor speed of head-fixed mice when they were delivered laser pulses at different stimulation frequency (ctrl, n=6 mice; ChR2, 7 mice). Controls are mCherry-expressing mice. Q, Quantification of maximal speed during activation of NI NMB neurons with different stimulation frequency (Mann Whitney test). R, Quantification of onset latency. **, P<0.01; ns, not significant. Error bars (E, K, Q, R) and shaded areas (F–I) indicate SEM.

  • Figure 2

    An optical BtBI transmits information regarding locomotor speed across brains. A, Schematic of the optical BtBI. We used fiber photometry to record the population Ca2+ signals of NI neurons from the Master mouse, transformed the signals to blue laser pulses, and delivered the laser pulses into the NI of the Avatar mouse. DM, dichroic mirror; PMT, photomultiplier tube; DAQ, data acquisition. B, Example traces showing, from the top to the bottom, the locomotor speed of the Master, the Ca2+ signal of NI neurons from the Master, the signal transformation formula, frequency modulation of light pulses, and the locomotor speed of the Avatar. C, Locomotor speeds of a representative BtBI dyad. D, Correlation between Master’s speed and Avatar’s speed (a representative BtTI dyad). Relative incidence means the probability of specific Master’s speed and the corresponding Avatar’s speed on all recording data. E, Group data showing the Pearson correlation coefficients of the control group (n=12 dyads) and the BtBI group (n=14 dyads). The control group consisted of GCaMP6-expressing Masters and mCherry-expressing non-responder mice. F, Average speed confusion matrix that consists of normalized Master speed and Avatar speed for every time point across all BtBI dyads (n=14). Color bar indicates confusion values normalized by row. G, Receiver Operating Characteristics (ROC) curves for a control dyad and an experiment dyad. The ROC curve is based on binarized data, with 0 indicating stationary and 1 movement. H, Group data showing the area under the ROC (AUROC) of the control group and the BtBI group. I, Group data showing the true positive rate of the control group and the BtBI group. Error bars (E, H, I) indicate SEM. ****, P<0.0001; Mann Whitney test.

  • Figure 3

    Evaluation of information transfer rate of the optical BtBI. A and B, Avatar followed Master during the acceleration (A) or deceleration (B) events of the Master mouse. Heatmaps illustrate the locomotor activity of the dyad for 12 events. Plots show the average speed of the two animals as a function of time relative to the event onset. C and D, Average locomotor speed of the total test group (n=14 dyads) during acceleration (C) and deceleration (D). E, Quantification of latency to start and latency to stop of Avatars. F and G, Information transfer (IT) rates (bits s–1, bps) from the Master to the Avatar. We measured the rate of mutual information between the locomotor motor speed of the Master and that of the Avatar during the acceleration (F) and deceleration (G) events. Heatmaps in the top panel show the information transfer rate of individual trials for one representative dyad. Bottom panels show the average information rates for the dyad as a function of time relative to the event onset and offset. H and I, Average information rate of the total test group (n=14 dyads). J, Quantification of information transfer rate of the control group (n=12 dyads) and the BtBI group (n=14 dyads). Mean information transfer rate is calculated during 0.5–3.5 s with data showed in H and Figure S2K in Supporting Information. Shaded areas (A–D, F–I) and error bars (E, J) indicate SEM. ****, P<0.0001; Mann Whitney test.

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