Distinct representations of olfactory information in different cortical centres

Journal name:
Nature
Volume:
472,
Pages:
213–216
Date published:
DOI:
doi:10.1038/nature09868
Received
Accepted
Published online

Sensory information is transmitted to the brain where it must be processed to translate stimulus features into appropriate behavioural output. In the olfactory system, distributed neural activity in the nose is converted into a segregated map in the olfactory bulb1, 2, 3. Here we investigate how this ordered representation is transformed in higher olfactory centres in mice. We have developed a tracing strategy to define the neural circuits that convey information from individual glomeruli in the olfactory bulb to the piriform cortex and the cortical amygdala. The spatial order in the bulb is discarded in the piriform cortex; axons from individual glomeruli project diffusely to the piriform without apparent spatial preference. In the cortical amygdala, we observe broad patches of projections that are spatially stereotyped for individual glomeruli. These projections to the amygdala are overlapping and afford the opportunity for spatially localized integration of information from multiple glomeruli. The identification of a distributive pattern of projections to the piriform and stereotyped projections to the amygdala provides an anatomical context for the generation of learned and innate behaviours.

At a glance

Figures

  1. Targeted electroporation of TMR-dextran labels cells that innervate a single glomerulus in the olfactory bulb.
    Figure 1: Targeted electroporation of TMR-dextran labels cells that innervate a single glomerulus in the olfactory bulb.

    a, b, A mouse olfactory bulb in which the MOR174-9 glomerulus is labelled with GFP, before (a) and after (b) electroporation with TMR-dextran. Scale bar,40μm. c, Image similar to a where electroporation was performed in a mouse in which spH is expressed in all glomeruli (OMP–IRES–spH, green); note that labelling (red) is confined to a single glomerulus. Scale bar,85μm. d, Control experiment in an OMP–IRES–spH mouse in which neighbouring glomeruli were electroporated with TMR-dextran (red, left) and FITC-dextran (green, right). Scale bar,45μm. e, Labelling of mitral cells (red, green) as a result of the experiment in d. f, Quantification of the overlap in mitral cell labelling in experiments similar to d (error bars represent s.e.m.; n = 4).

  2. Mitral/tufted cells connected to a single glomerulus show distinct patterns of projections to several areas of the olfactory cortex.
    Figure 2: Mitral/tufted cells connected to a single glomerulus show distinct patterns of projections to several areas of the olfactory cortex.

    a, A flattened hemi-brain preparation of the olfactory cortex with nuclei identified by counterstain (blue, NeuroTrace 435) and relevant structures outlined in white. AON, anterior olfactory nucleus; AMG, cortical amygdala; ENT, lateral entorhinal cortex; LOT, lateral olfactory tract; OT, olfactory tubercle; PIR, piriform cortex. b, A hemi-brain from a mouse in which a single glomerulus was electroporated with TMR-dextran (red). Note the unique pattern of projection in each of the olfactory areas. A, anterior; P, posterior; D, dorsal; V, ventral. Scale bar,700μm. See also Supplementary Fig. 3.

  3. Projections from single glomeruli to piriform cortex are disperse, homogeneous and indistinguishable.
    Figure 3: Projections from single glomeruli to piriform cortex are disperse, homogeneous and indistinguishable.

    ac, Images of axons innervating the piriform cortex (red) from mitral and tufted cells that connect to the glomerulus corresponding to MOR1-3 (a), MOR174-9 (b) or a random selection of glomeruli labelled with TMR-dextran (c). Scale bar, 500μm. df, Correlograms plotted using the matrix of correlation coefficients generated by normalized cross-correlation of two MOR1-3 piriforms (d), a MOR1-3 and a MOR174-9 piriform (e), and two piriforms in which random glomeruli were labelled (f). Cross-correlation is performed using aligned images of projection patterns as seen in ac. g, Autocorrelograms generated using methods from d in which a labelled piriform is compared to itself. Note that correlograms in g are essentially indistinguishable from the correlograms in df.

  4. Projections from single glomeruli to the cortical amygdala are broad, patchy and stereotyped.
    Figure 4: Projections from single glomeruli to the cortical amygdala are broad, patchy and stereotyped.

    ac, Images of the cortical amygdala reveal similar projections from the mitral and tufted cells that connect to the MOR1-3 glomerulus in two different brains (circlerepresents theapproximate posterolateral cortical nucleus boundary) (a), but projections that are distinct from those of mitral/tufted cells connected to the MOR28 glomerulus (b) or six randomly selected glomeruli (c). ‘D’ or ‘V’ in the bottom right corner of the image indicates whether the electroporated glomerulus was located dorsally or ventrally in the bulb. M, medial; L, lateral. Scale bar,400μm. df, Counterstained images from a subregion of images in ac showing a closer view of projection patterns. Scale bar,400μm. gi, Correlograms plotted using the matrix of correlation coefficients generated by normalized cross-correlation of MOR28 × MOR28 projection patterns within the posterolateral cortical amygdala (PLCo) (g), MOR1-3 × MOR1-3 projection patterns (h), or projection patterns from glomeruli of different types (i). j, Autocorrelograms of the PLCo from two labelled glomeruli correlated with themselves. Note that in the en bloc preparation shown here, the lateral/medial axis (indicated by the orientation bars) is synonymous with the dorsal/ventral axis, as this region of brain is curved.

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Author information

Affiliations

  1. Department of Neuroscience and the Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA

    • Dara L. Sosulski,
    • Maria Lissitsyna Bloom,
    • Tyler Cutforth,
    • Richard Axel &
    • Sandeep Robert Datta
  2. Present addresses: Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA (M.L.B., S.R.D.); Department of Molecular, Cell and Developmental Biology, University of California, Santa Cruz, California 95064, USA (T.C.).

    • Maria Lissitsyna Bloom,
    • Tyler Cutforth &
    • Sandeep Robert Datta

Contributions

S.R.D., D.L.S. and R.A conceived the project, participated in its development and wrote the manuscript. S.R.D. and D.L.S. developed methods and performed all experiments and data analysis. T.C. generated the MOR1-3 and MOR174-9–IRES–GFP mice. M.L.B. performed mouse husbandry and immunostaining.

Competing financial interests

The authors declare no competing financial interests.

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Supplementary information

Zip files

  1. Supplementary Information (24.9M)

    The file contains Supplementary Figures 1-12 with legends and Supplementary Tables 1-3.

Movies

  1. Supplementary Movie 1 (8M)

    Movie created using a z-stack of images taken using a two-photon microscope of the olfactory bulb of an OMP-IRES-spH mouse after electroporation of a single glomerulus with TMR dextran (red). The imaged plane descends from the glomerular layer (surface) of the olfactory bulb through the mitral cell layer (~300 microns deep) as the movie progresses.

Additional data