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Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons

Nature Neuroscience volume 12, pages 454–462 (2009)Cite this article

Abstract

In the nose, odorants are detected on the cilia of olfactory sensory neurons (OSNs), where a cAMP-mediated signaling pathway transforms odor stimulation into electrical responses. Phosphodiesterase (PDE) activity in OSN cilia has long been thought to account for rapid response termination by degrading odor-induced cAMP. Two PDEs with distinct cellular localization have been found in OSNs: PDE1C in the cilia and PDE4A throughout the cell but absent from the cilia. We disrupted both of these genes in mice and carried out electro-olfactogram analysis. Unexpectedly, eliminating PDE1C did not prolong response termination. Prolonged termination occurred only in mice that lacked both PDEs, suggesting that cAMP degradation by PDE1C in cilia is not a rate-limiting factor for response termination in wild-type mice. Pde1c−/− OSNs instead showed reduced sensitivity and attenuated adaptation to repeated stimulation, suggesting that PDE1C may be involved in regulating sensitivity and adaptation. Our observations provide new perspectives on the regulation of olfactory transduction.

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Figure 1: Molecular characterization of Pde1c−/−, Pde4a−/− and Pde1c−/−; Pde4a−/− mice.
Figure 2: Pde1c−/− OSNs show reduced EOG amplitude, faster response termination and slower onset kinetics.
Figure 3: Knockout of PDE1C eliminates all PDE activity from OSN cilia.
Figure 4: Pde4a−/− OSNs show no aberrant EOG response properties.
Figure 5: Pde1c−/−; Pde4a−/− double knockout mice show prolonged response termination and increased baseline noise.
Figure 6: OSN adaptation is differently affected in Pde1c−/− and Pde1c−/−; Pde4a−/− mice.
Figure 7: Computer modeling of degradation and diffusion of cilial cAMP.

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Acknowledgements

We thank J. Beavo for antibody to PDE1C2, J. Cherry for antibody to PDE4A and F. Margolis for antibody to OMP. We also thank L. Brand, R. Cone, S. Hattar, R. Kuruvilla, T. Leinders-Zufall, R. Reed, J. Reisert and Y. Song for suggestions and comments on experiments and the manuscript, and members of the Hattar, Kuruvilla, Zhao laboratory for discussion. This work was supported by US National Institutes of Health National Institute on Deafness and other Communications Disorders grant DC007395.

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  1. Department of Biology, the Johns Hopkins University, Baltimore, Maryland, USA

    Katherine D Cygnar & Haiqing Zhao

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  1. Katherine D Cygnar
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K.D.C. and H.Z. designed the experiments, K.D.C. collected the data, and both authors wrote the manuscript.

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Correspondence to Haiqing Zhao.

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Supplementary Figures 1–5, Supplementary Tables 1 and 2, and Supplementary Note (PDF 3424 kb)

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Cygnar, K., Zhao, H. Phosphodiesterase 1C is dispensable for rapid response termination of olfactory sensory neurons. Nat Neurosci 12, 454–462 (2009). https://doi.org/10.1038/nn.2289

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