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Odorant receptors instruct functional circuitry in the mouse olfactory bulb

Abstract

The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium1. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections2. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 → M71, in which a functionally characterized receptor, rI73,4, has been substituted into the M71 receptor locus5. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 → M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 → M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb.

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Figure 1: Odorant induced activation of rI7 → M71 glomeruli detected by intrinsic signal imaging.
Figure 2: rI7 → M71 glomeruli are innervated by postsynaptic neurons.
Figure 3: In vivo recording from a mitral cell responding to rI7 ligands.
Figure 4: Reciprocal connection between isofunctional glomeruli.

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Acknowledgements

We thank G. Feng for providing the YFP-G mice. L.C.K. is an Investigator in the Howard Hughes Medical Institute, L.B. is a Burroughs Wellcome Fellow in Neuroscience, and grant support to P.M. was from the NIH.

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Correspondence to Leonardo Belluscio.

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Belluscio, L., Lodovichi, C., Feinstein, P. et al. Odorant receptors instruct functional circuitry in the mouse olfactory bulb. Nature 419, 296–300 (2002). https://doi.org/10.1038/nature01001

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