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Letters to Nature

Nature 419, 296-300 (19 September 2002) | doi:10.1038/nature01001; Received 29 January 2002; Accepted 24 June 2002

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Odorant receptors instruct functional circuitry in the mouse olfactory bulb

Leonardo Belluscio1,2, Claudia Lodovichi1, Paul Feinstein3, Peter Mombaerts3 & Lawrence C. Katz1

  1. Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA
  2. The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA
  3. Present address: The National Institute of Neurological Disorders and Stroke, National Institutes of Health, 36 Convent Drive, Bethesda, Maryland 20892-4150, USA.

Correspondence to: Leonardo Belluscio1,2Peter Mombaerts3 Correspondence and requests for materials should be addressed to L.B. (e-mail: Email: belluscl@ninds.nih.gov).

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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 right arrow 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 right arrow M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 right arrow 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.