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Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons


Sensory information may be represented in the brain by stereotyped mapping of axonal inputs or by patterning that varies between individuals. In olfaction, a stereotyped map is evident in the first sensory processing centre, the olfactory bulb (OB), where different odours elicit activity in unique combinatorial patterns of spatially invariant glomeruli1,2. Activation of each glomerulus is relayed to higher cortical processing centres by a set of 20–50 ‘homotypic’ mitral and tufted (MT) neurons3. In the cortex, target neurons integrate information from multiple glomeruli to detect distinct features of chemically diverse odours4,5,6. How this is accomplished remains unclear, perhaps because the cortical mapping of glomerular information by individual MT neurons has not been described. Here we use new viral tracing and three-dimensional brain reconstruction methods to compare the cortical projections of defined sets of MT neurons. We show that the gross-scale organization of the OB is preserved in the patterns of axonal projections to one processing centre yet reordered in another, suggesting that distinct coding strategies may operate in different targets. However, at the level of individual neurons neither glomerular order nor stereotypy is preserved in either region. Rather, homotypic MT neurons from the same glomerulus innervate broad regions that differ between individuals. Strikingly, even in the same animal, MT neurons exhibit extensive diversity in wiring; axons of homotypic MT pairs diverge from each other, emit primary branches at distinct locations and 70–90% of branches of homotypic and heterotypic pairs are non-overlapping. This pronounced reorganization of sensory maps in the cortex offers an anatomic substrate for expanded combinatorial integration of information from spatially distinct glomeruli and predicts an unanticipated role for diversification of otherwise similar output neurons.

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Figure 1: Different organizations of MT axons in the AON and PC.
Figure 2: Three-dimensional reconstructions of individual M/T neurons reveal extensive branching and intrabulbar mapping.
Figure 3: Diverse patterns of glomerular inputs to the cortex.
Figure 4: Extensive diversity among homotypic MT neurons in the same animal.


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We wish to thank G. Patrick for the gift of pSin2gene virus and S. Djakovic for help with viral production. We thank O. Kwon and K. Spencer for assistance with imaging. We thank A. Maximov and J. Hazen for critical reading of the manuscript. We thank T. Cutforth for generating and R. Axel for supporting the generation of the ORT mouse strain, which was a gift. We thank the NCMIR, the Waitt Foundation and M. Ellisman for providing access to state-of-the-art imaging equipment and image processing tools. We thank the Baldwin and Cline lab members for providing laboratory support and advice. This work was supported by a Pew Scholars Award (K.K.B.) and support from the California Institute of Regenerative Medicine, the Whitehall Foundation, the O’Keefe Foundation, the Shapiro Family Foundation and the Dorris Neuroscience Center.

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Authors and Affiliations



S.D.L. developed code to transfer and align neuron traces in the WBC platform. H.H. performed sector and proximity analyses. Z.M., S.G. and K.D. generated the three-dimensional reconstructions of neurons. K.D. assisted generating the Reference Brain. T.C. generated the mOR174-9-GFP mouse strain and edited the manuscript. S.G. designed and performed experiments, analysed data and edited the manuscript. K.K.B. conceived of the experimental design, analysed data and wrote the manuscript.

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Correspondence to Kristin K. Baldwin.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-9 with legends. (PDF 7593 kb)

Supplementary Movie 1

This movie shows a 3-D reconstruction of a single neuron traced from the olfactory bulb into the cortex corresponding to Figure 2c. (MOV 14011 kb)

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Ghosh, S., Larson, S., Hefzi, H. et al. Sensory maps in the olfactory cortex defined by long-range viral tracing of single neurons. Nature 472, 217–220 (2011).

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