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Author Notes:

To whom correspondence should be addressed. Email:kressler@mclean.harvard.edu Edited by Joseph E. LeDoux, New York University, New York, NY, and approved September 8, 2015 (received for review March 12, 2015)

F.G.M., B.G.D., and K.J.R. designed research; F.G.M. and B.G.D. performed research; F.G.M., B.G.D., and K.J.R. contributed new reagents/analytic tools; F.G.M., B.G.D., and K.J.R. analyzed data; and F.G.M., B.G.D., and K.J.R. wrote the paper.

We thank the animal care staff in the Yerkes Neuroscience Vivarium for assistance with animal husbandry.

We also thank Kenneth McCullough, Stephanie Maddox, and Sunayana Banerjee for assistance with ensuring double-blindness of data acquisition and analysis; Kevin Ding for assistance with olfactory fear behavior; and members of the K.J.R. laboratory for thoughtful and helpful feedback on the manuscript and support.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Subjects:

Research Funding:

This work was supported by the following sources of funding: the National Institutes of Mental Health (1R01MH096764) (to K.J.R.), the Howard Hughes Medical Institute, and Ruth L. Kirstein National Research Service Award (NRSA) Predoctoral Fellowship F31 MH105237-01 (to F.G.M.).

This project was also funded by the Office of Research Infrastructure Programs/OD P51OD011132 [formerly National Center for Research Resources (NCRR) P51RR000165].

Keywords:

  • fear extinction
  • olfaction
  • neural plasticity

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 112, Number 41

Publisher:

, Pages 12846-12851

Type of Work:

Article | Final Publisher PDF

Abstract:

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learninginduced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.
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