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mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction

Title:

mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction

Liu, Dong, Stowie, Adam, de Zavalia, Nuria, Leise, Tanya, Pathak, Salil Saurav, Drewes, Lester R., Davidson, Alec J., Amir, Shimon ORCID: https://orcid.org/0000-0003-1919-5023, Sonenberg, Nahum and Cao, Ruifeng (2018) mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction. Proceedings of the National Academy of Sciences . pp. 1-9. ISSN 0027-8424

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Official URL: http://dx.doi.org/10.1073/pnas.1721578115

Abstract

Mammalian/mechanistic target of rapamycin (mTOR) signaling controls cell growth, proliferation, and metabolism in dividing cells. Less is known regarding its function in postmitotic neurons in the adult brain. Here we created a conditional mTOR knockout mouse model to address this question. Using the Cre-LoxP system, the mTOR gene was specifically knocked out in cells expressing Vip (vasoactive intestinal peptide), which represent a major population of interneurons widely distributed in the neocortex, suprachiasmatic nucleus (SCN), olfactory bulb (OB), and other brain regions. Using a combination of biochemical, behavioral, and imaging approaches, we found that mice lacking mTOR in VIP neurons displayed erratic circadian behavior and weakened synchronization among cells in the SCN, the master circadian pacemaker in mammals. Furthermore, we have discovered a critical role for mTOR signaling in mediating olfaction. Odor stimulated mTOR activation in the OB, anterior olfactory nucleus, as well as piriform cortex. Odor-evoked c-Fos responses along the olfactory pathway were abolished in mice lacking mTOR in VIP neurons, which is consistent with reduced olfactory sensitivity in these animals. Together, these results demonstrate that mTOR is a key regulator of SCN circadian clock synchrony and olfaction.

Divisions:Concordia University > Research Units > Centre for Studies in Behavioural Neurobiology
Item Type:Article
Refereed:Yes
Authors:Liu, Dong and Stowie, Adam and de Zavalia, Nuria and Leise, Tanya and Pathak, Salil Saurav and Drewes, Lester R. and Davidson, Alec J. and Amir, Shimon and Sonenberg, Nahum and Cao, Ruifeng
Journal or Publication:Proceedings of the National Academy of Sciences
Date:19 March 2018
Funders:
  • Faculty Start-Up Grant from the University of Minnesota Medical School
  • Canadian Institutes of Health Research Grants MOP7214
  • MOP142458
  • NIH Grant SC1 GM112567
Digital Object Identifier (DOI):10.1073/pnas.1721578115
Keywords:mTOR VIP SCN circadian clock olfaction
ID Code:983594
Deposited By: MONIQUE LANE
Deposited On:21 Mar 2018 20:16
Last Modified:21 Mar 2018 22:48

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