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A comprehensive thalamocortical projection map at the mesoscopic level

Nature Neuroscience volume 17, pages 1276–1285 (2014)Cite this article

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Abstract

The thalamus relays sensori-motor information to the cortex and is an integral part of cortical executive functions. The precise distribution of thalamic projections to the cortex is poorly characterized, particularly in mouse. We employed a systematic, high-throughput viral approach to visualize thalamocortical axons with high sensitivity. We then developed algorithms to directly compare injection and projection information across animals. By tiling the mouse thalamus with 254 overlapping injections, we constructed a comprehensive map of thalamocortical projections. We determined the projection origins of specific cortical subregions and verified that the characterized projections formed functional synapses using optogenetic approaches. As an important application, we determined the optimal stereotaxic coordinates for targeting specific cortical subregions and expanded these analyses to localize cortical layer–preferential projections. This data set will serve as a foundation for functional investigations of thalamocortical circuits. Our approach and algorithms also provide an example for analyzing the projection patterns of other brain regions.

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Figure 1: Systematic mapping of fluorescently labeled thalamocortical projections using high-throughput, high-resolution imaging.
Figure 2: Assessment of variability across brains, atlas alignment and injection coverage of the thalamus.
Figure 3: Localization of the thalamic origins of cortical projections.
Figure 4: Localizing thalamic subdivisions on the basis of cortical projection patterns.
Figure 5: Targeting anatomically defined thalamocortical projections to verify that they form functional synapses.
Figure 6: Nuclear localization of the thalamic origins of frontal projections.
Figure 7: Cortical layer preferences of thalamic projections to vM1.

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Acknowledgements

All Nanozoomer images were collected in Janelia Farm Research Campus. We thank C. Mello, M. Qin, J. Qiu, J. Li, S.K. Petrie, A. Gilmore, Y. Zuo and D. Lioy for technical support. We thank K. Svoboda, J. Lichtman, K. Huang and B. Li for their discussions, and K. Svoboda, J. Williams and J. Adelman for comments on the manuscript. We thank R. Champieux and K. Banerjee for establishing the web data depository. We thank K. Svoboda and HHMI, Janelia Farm Research Campus for their generous support in the initiation and data collection phase of this project. This work was supported by an American Recovery and Reinvestment Act grant (P30 NS069305, R. Goodman), a National Science Foundation Graduate Research Fellowship Program fellowship (B.J.H.), Achievement Rewards for College Scientists Foundation Portland Chapter (B.J.H.), a US National Institutes of Health Director's Innovator Award (DP2 OD008425, H.Z.), a US National Institutes of Health R01 grant (R01 NS081071, T.M.) and the Medical Research Foundation (T.M.).

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Author notes

  1. Brian R Long

    Present address: Present address: Allen Institute for Brain Science, Seattle, Washington, USA.,

  2. Barbara J Hunnicutt and Brian R Long: These authors contributed equally to the work.

Authors and Affiliations

  1. Vollum Institute, Oregon Health and Science University, Portland, Oregon, USA

    Barbara J Hunnicutt, Brian R Long, Deniz Kusefoglu, Katrina J Gertz, Haining Zhong & Tianyi Mao

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Contributions

All of the authors participated in designing the experiments. B.J.H., D.K., K.J.G. and T.M. performed the experiments. B.J.H., B.R.L., K.J.G., D.K., H.Z. and T.M. analyzed the data. B.J.H., B.R.L., K.J.G., H.Z. and T.M. wrote the manuscript.

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Correspondence to Haining Zhong or Tianyi Mao.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–14 and Supplementary Table 1 (PDF 4872 kb)

Supplementary Methods Checklist (PDF 357 kb)

Full confidence maps as 3D stacks for AI.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1649 kb)

Full confidence maps as 3D stacks for LO.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1602 kb)

Full confidence maps as 3D stacks for VO.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1592 kb)

Full confidence maps as 3D stacks for MO.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1596 kb)

Full confidence maps as 3D stacks for IL.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1589 kb)

Full confidence maps as 3D stacks for PrL.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1616 kb)

Full confidence maps as 3D stacks for vACC.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1620 kb)

Full confidence maps as 3D stacks for dACC.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1632 kb)

Full confidence maps as 3D stacks for FrA.

Distance from bregma for each section is indicated. All scale bars are 1 mm. (AVI 1683 kb)

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Hunnicutt, B., Long, B., Kusefoglu, D. et al. A comprehensive thalamocortical projection map at the mesoscopic level. Nat Neurosci 17, 1276–1285 (2014). https://doi.org/10.1038/nn.3780

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