Odorant stimulation enhances survival of olfactory sensory neurons via MAPK and CREB

Neuron. 2004 Mar 25;41(6):955-67. doi: 10.1016/s0896-6273(04)00075-3.


Olfactory sensory neurons (OSNs) can be sensitized to odorants by repeated exposure, suggesting that an animal's responsiveness to olfactory cues can be enhanced at the initial stage of detection. However, because OSNs undergo a regular cycle of apoptosis and replacement by ostensibly naive, precursor-derived neurons, the advantage of sensitization would be lost in the absence of a mechanism for odorant-enhanced survival of OSNs. Using recombinant adenoviruses in conjunction with surgical and electrophysiological techniques, we monitored OSN survival and function in vivo and find that odorant exposure selectively rescues populations of OSNs from apoptosis. We further demonstrate that odorant stimuli rescue OSNs in a cAMP-dependent manner by activating the MAPK/CREB-dependent transcriptional pathway, possibly as a result of expression of Bcl-2.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cell Survival / genetics*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Genetic Vectors / genetics
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Membrane Potentials / genetics
  • Mice
  • Mice, Inbred C57BL
  • Neurons, Afferent / cytology
  • Neurons, Afferent / enzymology*
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / enzymology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Odorant / genetics
  • Receptors, Odorant / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Smell / physiology


  • Cyclic AMP Response Element-Binding Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Odorant
  • Recombinant Fusion Proteins