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Mapping brain circuitry with a light microscope

The beginning of the 21st century has seen a renaissance in light microscopy and anatomical tract tracing that together are rapidly advancing our understanding of the form and function of neuronal circuits. The introduction of instruments for automated imaging of whole mouse brains, new cell type–specific and trans-synaptic tracers, and computational methods for handling the whole-brain data sets has opened the door to neuroanatomical studies at an unprecedented scale. We present an overview of the present state and future opportunities in charting long-range and local connectivity in the entire mouse brain and in linking brain circuits to function.

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Figure 1: Whole-brain LM methods.
Figure 2: Primary motor cortex projection maps.
Figure 3: Mapping the function and connectivity of single cells in the mouse brain in vivo.
Figure 4: Imaging induction of c-fos as a means to map whole-brain activation.

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Acknowledgements

We thank P. Mitra, H. Zeng and Christian Niedworok for comments on the manuscript and J. Kuhl for the graphics. P.O. is supported by the US National Institute of Mental Health grant 1R01MH096946-01, McKnight Foundation, Technological Innovations in Neuroscience Award and Simons Foundation for Autism Research grants 204719 and 253447. T.W.M. is supported as a Wellcome Trust Investigator and by the Medical Research Council MC U1175975156.

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Correspondence to Pavel Osten or Troy W Margrie.

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P.O. is the founder and shareholder of Certerra Inc., a contract research organization that uses STP tomography for central nervous system drug screening.

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Osten, P., Margrie, T. Mapping brain circuitry with a light microscope. Nat Methods 10, 515–523 (2013). https://doi.org/10.1038/nmeth.2477

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