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The Journal of Neuroscience, June 20, 2007, 27(25):6675-6683; doi:10.1523/JNEUROSCI.0699-07.2007

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Development/Plasticity/Repair
Absence of Adenylyl Cyclase 3 Perturbs Peripheral Olfactory Projections in Mice

Dong-Jing Zou, Alexander T. Chesler, Claire E. Le Pichon, Andriy Kuznetsov, Xin Pei, Eugene L. Hwang, and Stuart Firestein

Department of Biological Sciences, Columbia University, New York, New York 10027

Correspondence should be addressed to either Dong-Jing Zou or Stuart Firestein, 1212 Amsterdam Avenue, New York, NY 10027. Email: dz98{at}columbia.edu or Email: sjf24{at}columbia.edu

A remarkable feature of peripheral olfactory projections in mammals is the convergence of axons from olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) into the same glomeruli. There is mounting evidence that the ORs play critical roles in glomerular formation. However, it remains unclear how the OR exerts its function of sorting axons into homogeneity. We and others have shown previously that activation of the G-protein/cAMP signaling cascade underlies glomerular formation. Here, we further investigated whether establishment of the mature glomerular array requires adenylyl cyclase 3 (AC3), a key component of the OR-mediated cAMP-dependent signaling cascade. We found robust AC3 expression in both OSN cilia and axons during the period of active glomerular formation in neonatal mice. Examination of OR-tagged mice in an AC3 knock-out background revealed that the absence of AC3 drastically and differentially perturbed the formation of several representative glomeruli. Furthermore, heterogeneous glomeruli innervated by axons of multiple OSN populations persisted in such mice well into adulthood. In addition, reproducible aberrations in axonal projections in AC3–/– mice appeared to correlate with the activation of specific OR loci, regardless of the expressed receptor sequence, suggesting that OR expression is but one factor in determining OSN axonal projections. Together, our results indicate that cAMP signaling is critical for axonal sorting and the establishment of axonal identity.

Key words: glomerulus; activity-dependent; development; signal transduction; transgenic mice; plasticity

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Received Feb. 15, 2007; revised April 16, 2007; accepted May 14, 2007.

Correspondence should be addressed to either Dong-Jing Zou or Stuart Firestein, 1212 Amsterdam Avenue, New York, NY 10027. Email: dz98{at}columbia.edu or Email: sjf24{at}columbia.edu

This article has been cited by other articles:

				L. Belluscio and D. M. Cummings Charting Plasticity in the Regenerating Maps of the Mammalian Olfactory Bulb Neuroscientist, June 1, 2008; 14(3): 251 - 263. [Abstract] [PDF]

				J. H. Cho, M. Lepine, W. Andrews, J. Parnavelas, and J.-F. Cloutier Requirement for Slit-1 and Robo-2 in Zonal Segregation of Olfactory Sensory Neuron Axons in the Main Olfactory Bulb J. Neurosci., August 22, 2007; 27(34): 9094 - 9104. [Abstract] [Full Text] [PDF]

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