Chemical Senses Vol. 30 No. suppl 1 © Oxford University
Press 2005; all rights reserved
Regeneration and Rewiring the Olfactory Bulb
Department of Physiology, Virginia Commonwealth University, Richmond, VA 23298-0551, USA
Correspondence to be sent to: Richard M. Costanzo, e-mail: rcostanz{at}mail2.vcu.edu
Key words: neurogenesis, odorant receptor, olfactory glomeruli, olfactory neuron, topographical mapping,
During olfactory development axons from the sensory epithelium migrate to the
olfactory bulb and gradually establish connections with targeted glomeruli (Key and St John, 2002
). The spatial distribution
of these connections form the basis of a topographical mapping of odorant receptors onto
the olfactory bulb (Vassar et al.,
1994). The olfactory epithelium retains its capacity to undergo neurogenesis
long after development and odorant receptors continue to establish new connections in the
adult olfactory bulb. Remarkably, these newly rewired connections converge onto glomeruli
in specific areas of the bulb maintaining a topographical mapping of odorant receptors.
The preservation of this spatial mapping of odorant receptors onto the olfactory bulb
plays an essential role in the processing of olfactory information while disruption of
odorant maps results in impaired or altered olfactory function (Yee and Costanzo, 1998).
The olfactory system has become a popular model for the study of neural regeneration
and the rewiring of axons following injury. Lesions to the neuroepithelium, nerve fibers
and olfactory bulb all have disruptive effects on odorant receptor mapping. Regeneration
and the restoration of olfactory receptor connections depend upon the degree and type of
injury. For example, lesions to olfactory cells in the neuroepithelium are not reversible
if the basal cell layer is destroyed. However, when spared, regeneration of the basal
cells leads to a reconstitution of the sensory epithelium and a subsequent restoration of
olfactory function (Iwema et al.,
2004).
Recovery following olfactory nerve transection also depends on the degree of injury.
Extensive lesions involving damage to both the olfactory nerves and layers of the
olfactory bulb are more likely to produce scar tissue and gliosis, introducing mechanical
barriers to axon growth. Regenerating axons must penetrate or circumvent these obstacles
if they are to successfully rewire the olfactory bulb. Early studies of olfactory nerve
lesions used metal blade instruments. This often resulted in extensive damage to multiple
layers of the olfactory bulb as well as the scraping of bone and dura along the
cribriform plate. Very long recovery times were frequently needed to observe reconnected
axons within the olfactory bulb, and connections were often formed in areas of injury
extending well into the granule cell layer. Although new methods have been developed to
selectively lesion the olfactory nerves with minimal or no damage to the olfactory bulb
(Costanzo, 2000), regenerating nerve
fibers still face the spatial challenges introduced by the disruption of axon sheath
alignments at the cribriform plate. In spite of the many obstacles encountered when
rewiring the olfactory bulb after injury, the olfactory system maintains its capacity to
regenerate new axon processes and can reestablish functional connections with the
olfactory bulb.
Figure 1 illustrates the changes that occur in the rewiring of the olfactory bulbs of P2-tau-LacZ mice following nerve transection. Although regenerated axons retain their ability to converge and re-establish connections with glomeruli, these rewired connections are distributed across a very wide area of the olfactory bulb (Figure 1A) and there is significant disruption to the normal P2 odorant mapping pattern observed in control mice (Figure 1B).
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In addition to the wider spatial distribution of P2 labeled axons projecting to multiple glomeruli, histological observations of the olfactory bulb show that many glomeruli receive partial innervation by P2 axons. These findings suggest that after nerve transection, glomeruli in the olfactory bulb are no longer dominated by a single odorant subtype and that there is a competition among regenerating receptor axons to occupy synaptic sites within a glomerulus. This post lesion alteration in the rewiring of glomeruli may have significant functional consequences, especially for odor discrimination.
The inability of axons to accurately rewire the olfactory bulb and restore the spatial integrity of odorant receptor maps is more likely to occur following injury to the olfactory nerves and bulbs than to the neuroepithelium. When the olfactory nerves and bulbs are injured, regenerated axons must find new pathways or overcome barriers such as gliosis and the formation of scar tissue before they can reestablish connections with the bulb. In contrast, when injury is limited to the olfactory neuroepithelium, regenerating axons have access to intact nerve bundle sheaths that provide conduits to guide axons back to specific regions of the bulb.
Mechanisms that facilitate or inhibit the guidance of axons to specific targets in the olfactory bulb are topics of considerable interest. Axon–cell interactions, growth factors, the role of glia cells and axonal outgrowth and interaction with extracellular matrix molecules are all topics that need further investigation. These mechanisms are likely to play an important role in the rewiring of the olfactory bulb. Future studies directed at understanding these mechanisms may help in the development of new strategies to improve recovery and restore olfactory function following injury.
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References |
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 Top References |
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Costanzo, R.M. (2000) Rewiring the olfactory bulb: changes in odor maps following recovery from nerve transection. Chem. Senses, 25, 199–205.
Iwema, C.L., Fang, H., Kurtz, D.B., Youngentob, S.L. and Schwob, J.E. (2004) Odorant receptor expression patterns are restored in lesion-recovered rat olfactory epithelium. J. Neurosci., 24, 356–369.
Key, B. and St John, J. (2002) Axon navigation in the mammalian primary olfactory pathway: where to next? Chem. Senses, 27, 245–260.
Vassar, R., Chao, S.K., Sitcheran, R., Nunez, J.M., Vosshall, L.B. and Axel, R. (1994) Topographic organization of sensory projections to the olfactory bulb. Cell, 79, 981–991.[CrossRef][ISI][Medline]
Yee, K.K. and Costanzo, R.M. (1998) Changes in odor quality discrimination following recovery from olfactory nerve transection. Chem. Senses, 23, 513–519.
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