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Serotonergic modulation of odor input to the mammalian olfactory bulb

Nature Neuroscience volume 12, pages 784–791 (2009)Cite this article

Abstract

Centrifugal serotonergic fibers innervate the olfactory bulb, but the importance of these projections for olfactory processing is unclear. We examined serotonergic modulation of sensory input to olfactory glomeruli using mice that express synaptopHluorin in olfactory receptor neurons (ORN). Odor-evoked synaptic input to glomeruli was attenuated by increased serotonin signaling through serotonin 2C (5-HT2C) receptors and amplified by decreased serotonergic activity. Intravital multiphoton calcium imaging revealed that 5-HT2C receptor activation amplified odor-evoked activity in a subset of juxtaglomerular cells and attenuated glutamate release from ORN terminals via GABAB receptors. Endogenous serotonin released by electrical stimulation of the dorsal raphe nucleus attenuated odor-evoked responses without detectable bias in glomerular position or odor identity. Weaker glomerular responses, however, were less sensitive to raphe stimulation than strong responses. Our data indicate that the serotonergic system regulates odor inputs in the olfactory bulb and suggest that behavioral states may alter odor processing at the earliest stages.

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Figure 1: Odor-evoked activity of sensory nerve terminals measured in Omp-spH mice and its modulation by serotonin receptors.
Figure 2: Immunohistochemistry reveals 5-HT2C receptor expression by some juxtaglomerular cells, but not by ORN terminals.
Figure 3: Multiphoton imaging reveals 5-HT modulation of juxtaglomerular cell activity.
Figure 4: Modulation of odor-evoked responses by 5-HT receptor ligands is occluded by antagonists of GABAB receptors.
Figure 5: Stimulation of dorsal raphe nucleus triggers a reversible reduction in odor-evoked input to the bulb.
Figure 6: Serotonergic modulation across different response amplitudes.

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Acknowledgements

We thank T. Sato for writing data acquisition and analysis software for all the microscopy, G. Szabo for the GAD65-GFP mice and the members of the Murthy laboratory for numerous discussions. This work was supported in part by the Marie Curie Fellowship Program of the European Union (G.C.P.).

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  1. Gabor C Petzold

    Present address: Present address: Department of Experimental Neurology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany.,

Authors and Affiliations

  1. Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA

    Gabor C Petzold, Akari Hagiwara & Venkatesh N Murthy

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Contributions

G.C.P. and V.N.M. conceived the project. G.C.P. and A.H. conducted the experiments. G.C.P. and V.N.M. analyzed the data and wrote the manuscript.

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Correspondence to Gabor C Petzold or Venkatesh N Murthy.

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Petzold, G., Hagiwara, A. & Murthy, V. Serotonergic modulation of odor input to the mammalian olfactory bulb. Nat Neurosci 12, 784–791 (2009). https://doi.org/10.1038/nn.2335

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