Abstract
The nearly 2,000 glomeruli that cover the surface of the olfactory bulb are so distinctive that they were noted specifically in the earliest of Cajal's catalogues. They have variously been considered a functional unit, an organizational unit and a crucial component of the olfactory coding circuit. Despite their central position in olfactory processing, the development of the glomeruli has only recently begun to be investigated with new and powerful genetic tools. Some unexpected findings have been made that may lead to a new understanding of the processes involved in wiring sensory regions of the brain. It may no longer be sufficient to simply invoke genes, spikes and their interplay in the construction of brain circuits. The story of 'how the olfactory bulb got its glomeruli' may be more complex, and more revealing, than has been supposed.
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References
Mori, K., Nagao, H. & Yoshihara, Y. The olfactory bulb: coding and processing of odor molecule information. Science 286, 711–715 (1999).
Mori, K., Takahashi, Y. K., Igarashi, K. M. & Yamaguchi, M. Maps of odorant molecular features in the mammalian olfactory bulb. Physiol. Rev. 86, 409–433 (2006).
Johnson, B. A. & Leon, M. Chemotopic odorant coding in a mammalian olfactory system. J. Comp. Neurol. 503, 1–34 (2007).
Ressler, K. J., Sullivan, S. L. & Buck, L. B. Information coding in the olfactory system: evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell 79, 1245–1255 (1994).
Vassar, R. et al. Topographic organization of sensory projections to the olfactory bulb. Cell 79, 981–991 (1994).
Mombaerts, P. et al. Visualizing an olfactory sensory map. Cell 87, 675–686 (1996).
Treloar, H. B., Feinstein, P., Mombaerts, P. & Greer, C. A. Specificity of glomerular targeting by olfactory sensory axons. J. Neurosci. 22, 2469–2477 (2002).
Wang, F., Nemes, A., Mendelsohn, M. & Axel, R. Odorant receptors govern the formation of a precise topographic map. Cell 93, 47–60 (1998).
Feinstein, P. & Mombaerts, P. A contextual model for axonal sorting into glomeruli in the mouse olfactory system. Cell 117, 817–831 (2004).
Feinstein, P., Bozza, T., Rodriguez, I., Vassalli, A. & Mombaerts, P. Axon guidance of mouse olfactory sensory neurons by odorant receptors and the β2 adrenergic receptor. Cell 117, 833–846 (2004).
Bozza, T., Feinstein, P., Zheng, C. & Mombaerts, P. Odorant receptor expression defines functional units in the mouse olfactory system. J. Neurosci. 22, 3033–3043 (2002).
Chess, A., Simon, I., Cedar, H. & Axel, R. Allelic inactivation regulates olfactory receptor gene expression. Cell 78, 823–834 (1994).
Malnic, B., Hirono, J., Sato, T. & Buck, L. B. Combinatorial receptor codes for odors. Cell 96, 713–723 (1999).
Mombaerts, P. Odorant receptor gene choice in olfactory sensory neurons: the one receptor–one neuron hypothesis revisited. Curr. Opin. Neurobiol. 14, 31–36 (2004).
Tian, H. & Ma, M. Activity plays a role in eliminating olfactory sensory neurons expressing multiple odorant receptors in the mouse septal organ. Mol. Cell Neurosci. 38, 484–488 (2008).
Goodman, C. S. & Shatz, C. J. Developmental mechanisms that generate precise patterns of neuronal connectivity. Cell 72S, 77–98 (1993).
Katz, L. C. & Shatz, C. J. Synaptic activity and the construction of cortical circuits. Science 274, 1132–1138 (1996).
Luo, L. & Flanagan, J. G. Development of continuous and discrete neural maps. Neuron 56, 284–300 (2007).
Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187 (1991).
Firestein, S. How the olfactory system makes sense of scents. Nature 413, 211–218 (2001).
Belluscio, L., Lodovichi, C., Feinstein, P., Mombaerts, P. & Katz, L. C. Odorant receptors instruct functional circuitry in the mouse olfactory bulb. Nature 419, 296–300 (2002).
Illig, K. R. & Eudy, J. D. Contralateral projections of the rat anterior olfactory nucleus. J. Comp. Neurol. 512, 115–123 (2009).
Yan, Z. et al. Precise circuitry links bilaterally symmetric olfactory maps. Neuron 58, 613–624 (2008).
Allison, A. C. The structure of the olfactory bulb and its relationship to the olfactory pathways in the rabbit and the rat. J. Comp. Neurol. 98, 309–353 (1953).
Aungst, J. L. et al. Centre-surround inhibition among olfactory bulb glomeruli. Nature 426, 623–629 (2003).
Llinas, R. R. The contribution of Santiago Ramon y Cajal to functional neuroscience. Nature Rev. Neurosci. 4, 77–80 (2003).
Soucy, E. R., Albeanu, D. F., Fantana, A. L., Murthy, V. N. & Meister, M. Precision and diversity in an odor map on the olfactory bulb. Nature Neurosci. 12, 210–220 (2009).
Egana, J. I., Aylwin, M. L. & Maldonado, P. E. Odor response properties of neighboring mitral/tufted cells in the rat olfactory bulb. Neuroscience 134, 1069–1080 (2005).
Fantana, A. L., Soucy, E. R. & Meister, M. Rat olfactory bulb mitral cells receive sparse glomerular inputs. Neuron 59, 802–814 (2008).
Tsuboi, A. et al. Olfactory neurons expressing closely linked and homologous odorant receptor genes tend to project their axons to neighboring glomeruli on the olfactory bulb. J. Neurosci. 19, 8409–8418 (1999).
Zhang, X. et al. High-throughput microarray detection of olfactory receptor gene expression in the mouse. Proc. Natl Acad. Sci. USA 101, 14168–14173 (2004).
Mombaerts, P. targeting olfaction. Curr. Op Neurobio. 6, 481–486 (1996).
Belluscio, L., Gold, G. H., Nemes, A. & Axel, R. Mice deficient in Golf are anosmic. Neuron 20, 69–81 (1998).
Baker, H. et al. Targeted deletion of a cyclic nucleotide-gated channel subunit (OCNC1): biochemical and morphological consequences in adult mice. J. Neurosci. 19, 9313–9321 (1999).
Lin, D. M. et al. Formation of precise connections in the olfactory bulb occurs in the absence of odorant-evoked neuronal activity. Neuron 26, 69–80 (2000).
Zheng, C., Feinstein, P., Bozza, T., Rodriguez, I. & Mombaerts, P. Peripheral olfactory projections are differentially affected in mice deficient in a cyclic nucleotide-gated channel subunit. Neuron 26, 81–91 (2000).
Bulfone, A. et al. An olfactory sensory map develops in the absence of normal projection neurons or GABAergic interneurons. Neuron 21, 1273–1282 (1998).
St. John, J. A., Clarris, H. J., McKeown, S., Royal, S. & Key, B. Sorting and convergence of primary olfactory axons are independent of the olfactory bulb. J. Comp. Neurol. 464, 131–140 (2003).
Zou, D. J. et al. Postnatal refinement of peripheral olfactory projections. Science 304, 1976–1979 (2004).
Nakatani, H., Serizawa, S., Nakajima, M., Imai, T. & Sakano, H. Developmental elimination of ectopic projection sites for the transgenic OR gene that has lost zone specificity in the olfactory epithelium. Eur. J. Neurosci. 18, 2425–2432 (2003).
Kerr, M. A. & Belluscio, L. Olfactory experience accelerates glomerular refinement in the mammalian olfactory bulb. Nature Neurosci. 9, 484–486 (2006).
Yu, C. R. et al. Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42, 553–566 (2004).
Wong, S. T. et al. Disruption of the type III adenylyl cyclase gene leads to peripheral and behavioral anosmia in transgenic mice. Neuron 27, 487–497 (2000).
Trinh, K. & Storm, D. R. Vomeronasal organ detects odorants in absence of signaling through main olfactory epithelium. Nature Neurosci. 6, 519–525 (2003).
Col, J. A., Matsuo, T., Storm, D. R. & Rodriguez, I. Adenylyl cyclase-dependent axonal targeting in the olfactory system. Development 134, 2481–2489 (2007).
Zou, D. J. et al. Absence of adenylyl cyclase 3 perturbs peripheral olfactory projections in mice. J. Neurosci. 27, 6675–6683 (2007).
Chesler, A. T. et al. A G. protein/cAMP signal cascade is required for axonal convergence into olfactory glomeruli. Proc. Natl Acad. Sci. USA 104, 1039–1044 (2007).
Katada, S., Tanaka, M. & Touhara, K. Structural determinants for membrane trafficking and G. protein selectivity of a mouse olfactory receptor. J. Neurochem. 90, 1453–1463 (2004).
Menco, B., Tedula, F., Farbman, A. & Danho, W. Developmental expression of G-proteins and adenylyl cyclase in peripheral olfactory systems. Light microscopic and freeze-substitution electron microscopic immunocytochemistry. J. Neurocytol. 23, 708–727 (1994).
Imai, T., Suzuki, M. & Sakano, H. Odorant receptor-derived cAMP signals direct axonal targeting. Science 314, 657–661 (2006).
Cutforth, T. et al. Axonal ephrin-As and odorant receptors: coordinate determination of the olfactory sensory map. Cell 114, 311–322 (2003).
Serizawa, S. et al. A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting. Cell 127, 1057–1069 (2006).
Kaneko-Goto, T., Yoshihara, S., Miyazaki, H. & Yoshihara, Y. BIG-2 mediates olfactory axon convergence to target glomeruli. Neuron 57, 834–846 (2008).
Bozza, T. et al. Mapping of class I and class II odorant receptors to glomerular domains by two distinct types of olfactory sensory neurons in the mouse. Neuron 61, 220–233 (2009).
Rothman, A., Feinstein, P., Hirota, J. & Mombaerts, P. The promoter of the mouse odorant receptor gene M71. Mol. Cell Neurosci. 28, 535–546 (2005).
Vassalli, A., Rothman, A., Feinstein, P., Zapotocky, M. & Mombaerts, P. Minigenes impart odorant receptor-specific axon guidance in the olfactory bulb. Neuron 35, 681. (2002).
Ishii, T. et al. Monoallelic expression of the odorant receptor gene and axonal projection of olfactory sensory neurones. Genes Cells 6, 71–78 (2001).
Serizawa, S. et al. Mutually exclusive expression of odorant receptor transgenes. Nature Neurosci. 3, 687–693 (2000).
Norlin, E. M. et al. Evidence for gradients of gene expression correlating with zonal topography of the olfactory sensory map. Mol. Cell Neurosci. 18, 283–295 (2001).
Cloutier, J. F. et al. Differential requirements for semaphorin 3F and Slit-1 in axonal targeting, fasciculation, and segregation of olfactory sensory neuron projections. J. Neurosci. 24, 9087–9096 (2004).
Cho, J. H., Lepine, M., Andrews, W., Parnavelas, J. & Cloutier, J. F. Requirement for Slit-1 and Robo-2 in zonal segregation of olfactory sensory neuron axons in the main olfactory bulb. J. Neurosci. 27, 9094–9104 (2007).
Walz, A., Rodriguez, I. & Mombaerts, P. Aberrant sensory innervation of the olfactory bulb in neuropilin-2 mutant mice. J. Neurosci. 22, 4025–4035 (2002).
Alenius, M. & Bohm, S. Differential function of RNCAM isoforms in precise target selection of olfactory sensory neurons. Development 130, 917–927 (2003).
Schwarting, G. A. et al. Semaphorin 3A is required for guidance of olfactory axons in mice. J. Neurosci. 20, 7691–7697 (2000).
Taniguchi, M. et al. Distorted odor maps in the olfactory bulb of semaphorin 3A-deficient mice. J. Neurosci. 23, 1390–1397 (2003).
Hasegawa, S. et al. The protocadherin-α family is involved in axonal coalescence of olfactory sensory neurons into glomeruli of the olfactory bulb in mouse. Mol. Cell Neurosci. 38, 66–79 (2008).
Walz, A., Feinstein, P., Khan, M. & Mombaerts, P. Axonal wiring of guanylate cyclase-D-expressing olfactory neurons is dependent on neuropilin 2 and semaphorin 3F. Development 134, 4063–4072 (2007).
Alenius, M. & Bohm, S. Identification of a novel neural cell adhesion molecule-related gene with a potential role in selective axonal projection. J. Biol. Chem. 272, 26083–26086 (1997).
Yoshihara, Y. et al. OCAM: a new member of the neural cell adhesion molecule family related to zone-to-zone projection of olfactory and vomeronasal axons. J. Neurosci. 17, 5830–5842 (1997).
Oka, Y. et al. O-MACS, a novel member of the medium-chain acyl-CoA synthetase family, specifically expressed in the olfactory epithelium in a zone-specific manner. Eur. J. Biochem. 270, 1995–2004 (2003).
Gussing, F. & Bohm, S. NQO1 activity in the main and the accessory olfactory systems correlates with the zonal topography of projection maps. Eur. J. Neurosci. 19, 2511–2518 (2004).
Strotmann, J. et al. Local permutations in the glomerular array of the mouse olfactory bulb. J. Neurosci. 20, 6927–6938 (2000).
Schaefer, M. L., Finger, T. E. & Restrepo, D. Variability of position of the P2 glomerulus within a map of the mouse olfactory bulb. J. Comp. Neurol. 436, 351–362 (2001).
Maresh, A., Gil, D. R., Whitman, M. C. & Greer, C. A. Principles of glomerular organization in the human olfactory bulb--implications for odor processing. PLoS ONE 3, e2640 (2008).
Zhang, X. et al. Characterizing the expression of the human olfactory receptor gene family using a novel DNA microarray. Genome Biol. 8, R86 (2007).
Pomeroy, S. L., LaMantia, A. S. & Purves, D. Postnatal construction of neural circuitry in the mouse olfactory bulb. J. Neurosci. 10, 1952–1966 (1990).
LaMantia, A. S., Pomeroy, S. L. & Purves, D. Vital imaging of glomeruli in the mouse olfactory bulb. J. Neurosci. 12, 976–988 (1992).
LaMantia AS & D, P. Development of glomerular pattern visualized in the olfactory bulbs of living mice. Nature 341, 646–649 (1989).
Barnea, G. et al. Odorant receptors on axon termini in the brain. Science 304, 1468 (2004).
Strotmann, J., Levai, O., Fleischer, J., Schwarzenbacher, K. & Breer, H. Olfactory receptor proteins in axonal processes of chemosensory neurons. J. Neurosci. 24, 7754–7761 (2004).
Ito, I., Ong, R. C., Raman, B. & Stopfer, M. Sparse odor representation and olfactory learning. Nature Neurosci. 11, 1177–1184 (2008).
Laurent, G. et al. Odor encoding as an active, dynamical process: experiments, computation, and theory. Annu. Rev. Neurosci. 24, 263–297 (2001).
Stevenson, R. J. & Wilson, D. A. Odour perception: an object-recognition approach. Perception 36, 1821–1833 (2007).
Barnes, D. C., Hofacer, R. D., Zaman, A. R., Rennaker, R. L. & Wilson, D. A. Olfactory perceptual stability and discrimination. Nature Neurosci. 11, 1378–1380 (2008).
Potter, S. M. et al. Structure and emergence of specific olfactory glomeruli in the mouse. J. Neurosci. 21, 9713–9723 (2001).
Bailey, M. S., Puche, A. C. & Shipley, M. T. Development of the olfactory bulb: evidence for glia–neuron interactions in glomerular formation. J. Comp. Neurol. 415, 423–448 (1999).
Royal, S. J. & Key, B. Development of P2 olfactory glomeruli in P2-internal ribosome entry site-tau-LacZ transgenic mice. J. Neurosci. 19, 9856–9864 (1999).
Treloar, H. B., Purcell, A. L. & Greer, C. A. Glomerular formation in the developing rat olfactory bulb. J. Comp. Neurol. 413, 289–304 (1999).
Zhao, H. & Reed, R. R. X inactivation of the OCNC1 channel gene reveals a role for activity-dependent competition in the olfactory system. Cell 104, 651–660 (2001).
Watt, W. C. et al. Odorant stimulation enhances survival of olfactory sensory neurons via MAPK and CREB. Neuron 41, 955–967 (2004).
Rubin, B. D. & Katz, L. C. Optical imaging of odorant representations in the mammalian olfactory bulb. Neuron 23, 499–511 (1999).
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The authors have been suported by grants from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health, USA.
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Zou, DJ., Chesler, A. & Firestein, S. How the olfactory bulb got its glomeruli: a just so story?. Nat Rev Neurosci 10, 611–618 (2009). https://doi.org/10.1038/nrn2666
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DOI: https://doi.org/10.1038/nrn2666
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