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mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction

Dong Liu1, Adam Stowie2, Nuria de Zavalia3

  • 1Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812.

Proceedings of the National Academy of Sciences of the United States of America
|March 21, 2018
PubMed

Insights

Mammalian target of rapamycin (mTOR) signaling is crucial for circadian clock synchrony in the suprachiasmatic nucleus and for olfaction in mice lacking mTOR in VIP neurons.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Chronobiology

Background:

  • Mammalian target of rapamycin (mTOR) signaling regulates cell growth and metabolism in dividing cells.
  • Its function in postmitotic neurons within the adult brain remains less understood.

Purpose of the Study:

  • To investigate the role of mTOR signaling in VIP (vasoactive intestinal peptide) neurons in the adult brain.
  • To elucidate mTOR's function in circadian rhythms and olfaction.

Main Methods:

  • Generated a conditional mTOR knockout mouse model using the Cre-LoxP system, specifically targeting VIP neurons.
  • Employed biochemical, behavioral, and imaging techniques to assess circadian behavior, SCN cell synchrony, and olfactory responses.
  • Measured odor-evoked c-Fos expression along the olfactory pathway.

Main Results:

  • Mice lacking mTOR in VIP neurons exhibited disrupted circadian behavior and reduced SCN cell synchrony.
  • mTOR activation was observed in the olfactory pathway upon odor stimulation.
  • Odor-evoked neuronal activation (c-Fos) was abolished in knockout mice, indicating impaired olfaction.

Conclusions:

  • mTOR signaling is essential for maintaining circadian clock synchrony within the suprachiasmatic nucleus.
  • mTOR plays a critical role in mediating olfactory processing and sensitivity.
Keywords:
SCNVIPcircadian clockmTORolfaction

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