Abstract
In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of ‘starter’ cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.
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Acknowledgements
We thank Stanford Transgenic Facility for help in generating transgenic mice, F. Zhang and K. Deisseroth for teaching us stereotactic injection, Y. Yoshihara and H. Zeng for reagents, C. Manalac and M. Shu for technical assistance, R. Axel, L. Buck, and L. Stryer, R. Yuste and members of the L.L. laboratory for discussion and critical reading of the manuscript. K.M. was supported by the JSPS program for Research Abroad and Human Frontier Science Program. K.M. is currently a research associate and L.L. is an investigator of the Howard Hughes Medical Institute. This work was also supported by an NIH grant.
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K.M. planned and performed all the experiments. F.A. and F.M. developed the computer programs for 3D reconstructions and statistical simulation under the supervision of M.A.H. C.W. and Z.H. performed the initial AAV production. I.W., N.R.W. and E.M.C. provided the modified rabies virus and the construct to make the AAV vector. H.T. and Z.J.H. provided the GAD2-CreER mice. B.T. provided DNA constructs. L.L. supervised the project. L.L. and K.M. wrote the manuscript, with contributions from B.T.
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Supplementary Information
The file contains Supplementary Figures 1-13 with legends, Supplementary Table 1 and additional references. (PDF 2324 kb)
Supplementary Movie 1
This movie shows 3D-reconstruciton of an olfactory bulb corresponding to Figure 2c and Supplemental Figure 8. (MP4 8129 kb)
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Miyamichi, K., Amat, F., Moussavi, F. et al. Cortical representations of olfactory input by trans-synaptic tracing. Nature 472, 191–196 (2011). https://doi.org/10.1038/nature09714
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DOI: https://doi.org/10.1038/nature09714
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