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Timing of neurogenesis is a determinant of olfactory circuitry

Nature Neuroscience volume 14, pages 331–337 (2011)Cite this article

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Abstract

An odorant receptor map in mammals that is constructed by the glomerular coalescence of sensory neuron axons in the olfactory bulb is essential for proper odor information processing. How this map is linked with olfactory cortex is unknown. Using a battery of methods, including various markers of cell division in combination with tracers of neuronal connections and time-lapse live imaging, we found that early- and late-generated mouse mitral cells became differentially distributed in the dorsal and ventral subdivisions of the odorant receptor map. In addition, the late-generated mitral cells extended substantially stronger projections to the olfactory tubercle than did the early-generated cells. Together, these data indicate that the odorant receptor map is developmentally linked to the olfactory cortices in part by the birthdate of mitral cells. Thus, different olfactory cortical regions become involved in processing information from distinct regions of the odorant receptor map.

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Figure 1: Distributions of mitral cells with different birthdates in the olfactory bulb.
Figure 2: Preferential integration of late-generated mitral cells into the ventrolateral developing olfactory bulb.
Figure 3: Tangential migration of late-generated mitral cells in the developing olfactory bulb.
Figure 4: Direct contact of E12-generated mitral cells with pre-existing mitral cell axons.
Figure 5: Birthdate-regulated axonal projection to the olfactory tubercle.

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Acknowledgements

We thank K. Mori for the antibody to OCAM, Y. Yoshihara for the antibody to Tbx21, A. Bordey for the DCX-GFP mice and all of the members of the Greer, Rakic and Treloar laboratories for technical assistance and discussion. The antibody to RC2 developed by M. Yamamoto was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the US National Institute of Child Health and Human Development and maintained by the Department of Biology, University of Iowa. This work was supported by the US National Institute of Health and the Kavli Institute for Neuroscience at Yale.

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Authors and Affiliations

  1. Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA

    Fumiaki Imamura & Charles A Greer

  2. Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut, USA

    Albert E Ayoub, Pasko Rakic & Charles A Greer

  3. The Kavli Institute of Neuroscience, Yale University School of Medicine, New Haven, Connecticut, USA

    Albert E Ayoub & Pasko Rakic

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  1. Fumiaki Imamura
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Contributions

F.I. and C.A.G. designed the study, analyzed data and wrote the manuscript. F.I. conducted the experiments. Time-lapse live imaging was done by F.I. and A.E.A. F.I., C.A.G., A.E.A. and P.R. discussed the results and commented on the manuscript.

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Correspondence to Charles A Greer.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 (PDF 3319 kb)

Supplementary Video 1

Tangential migration of cells in the developing olfactory bulb. Time-lapse images were taken from an E14 DCX-GFP olfactory bulb. An arrow indicates the tangentially migrating cell moving toward the posterior portion (down side of the image) of the olfactory bulb. Images were captured every 10 minutes. (MOV 1145 kb)

Supplementary Video 2

Radial migration of cells in the developing olfactory bulb. Time-lapse images were taken from an E14 DCX-GFP olfactory bulb. An arrow indicates the radially migrating cell in the ventricular zone moving toward the olfactory bulb surface. Images were captured every 10 minutes. (MOV 870 kb)

Supplementary Video 3

Radial to tangential change of migrating orientation of cells in developing olfactory bulb. Time-lapse images were taken from an E15 DCX-GFP olfactory bulb. An arrow shows the cell that changes orientation from radial to tangential at the interface of ventricular zone and intermediate zone. Images were captured every 10 minutes. (MOV 1128 kb)

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Imamura, F., Ayoub, A., Rakic, P. et al. Timing of neurogenesis is a determinant of olfactory circuitry. Nat Neurosci 14, 331–337 (2011). https://doi.org/10.1038/nn.2754

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