mTORC2, but not mTORC1, is required for hippocampal mGluR-LTD and associated behaviors

Nat Neurosci. 2018 Jun;21(6):799-802. doi: 10.1038/s41593-018-0156-7. Epub 2018 May 21.

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) has been reported to be necessary for metabotropic glutamate receptor-mediated long-term depression (mGluR-LTD). Here we found that mTORC1-deficient mice exhibit normal hippocampal mGluR-LTD and associated behaviors. Moreover, rapamycin blocks mGluR-LTD in mTORC1-deficient mice. However, both rapamycin and mGluR activation regulate mTOR complex 2 (mTORC2) activity, and mTORC2-deficient mice show impaired mGluR-LTD and associated behaviors. Thus, mTORC2 is a major regulator of mGluR-LTD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Electrophysiological Phenomena / physiology
  • Female
  • Hippocampus / physiology*
  • Learning / physiology
  • Long-Term Synaptic Depression / genetics*
  • Long-Term Synaptic Depression / physiology*
  • Male
  • Mechanistic Target of Rapamycin Complex 1 / genetics*
  • Mechanistic Target of Rapamycin Complex 1 / physiology*
  • Mechanistic Target of Rapamycin Complex 2 / genetics*
  • Mechanistic Target of Rapamycin Complex 2 / physiology*
  • Memory / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Metabotropic Glutamate / physiology*
  • Recognition, Psychology
  • Regulatory-Associated Protein of mTOR / genetics
  • Regulatory-Associated Protein of mTOR / physiology
  • Sirolimus / pharmacology
  • Space Perception / physiology

Substances

  • Receptors, Metabotropic Glutamate
  • Regulatory-Associated Protein of mTOR
  • Rptor protein, mouse
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Sirolimus